TARGETING INFLAMMATION IN ATHEROSCLEROSIS: INSIGHTS FROM NATURAL AND CONVENTIONAL THERAPIES
Main Article Content
Keywords
Inflammation, Atherosclerosis, Natural Products, Clinical trials
Abstract
Atherosclerosis, a cardiovascular disease is known to be one of the major causes of mortality across the globe. It has been predicted that within few years atherosclerosis will be responsible for much greater number of worldwide mortalities. Cardiovascular disease accounts for primary number of all deaths in North America and European countries [1]. Atherosclerosis is derived from the Greek words ‘athero’ meaning paste and ‘sclerosis’ which means hardening. Atherosclerosis is a multifactorial disease characterized by immune-inflammatory processes and lipid deposition in arterial walls, leading to plaque formation and progressive narrowing of blood vessels [2]. This pathology is a major cause of coronary artery disease, myocardial infarction, and stroke. While elevated low-density lipoprotein cholesterol (LDL-C), hypertension, and smoking are established risk factors, emerging contributors such as poor sleep, sedentary lifestyle, microbiome imbalance, environmental pollutants, and psychological stress are increasingly recognized. Together, these factors accelerate plaque growth, vascular dysfunction, and thrombus formation, culminating in severe cardiovascular events.
Therapeutic approaches for atherosclerosis target both lipid accumulation and inflammation. Natural compounds like Secoisolariciresinol Diglucoside (SDG), flaxseed lignans, flavonoids (quercetin, anthocyanins), and the medicinal plant Sphaeranthus indicus demonstrate lipid-lowering, antioxidant, and anti-inflammatory effects. Canakinumab, an anti-inflammatory biologic, and Ninjurin1 (NINJ1), a novel immune modulator, show promise as emerging targets. Alongside these, conventional drugs such as nifedipine, ramipril, and perindopril remain critical in managing blood pressure and reducing cardiovascular risk.
This review emphasizes the interplay of traditional and non-traditional risk factors in atherosclerosis while outlining both established and innovative therapeutic strategies aimed at reducing disease burden and improving cardiovascular outcomes.
References
Herrington, W., Lacey, B., Sherliker, P., Armitage, J., & Lewington, S. (2016). Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circulation research, 118(4), 535-546.
[2] Kawai, K., Finn, A. V., & Virmani, R. (2024). Subclinical Atherosclerosis: Part 1: What is it? Can it Be Defined at the Histological Level? Arteriosclerosis, Thrombosis, and Vascular Biology, 44(1), 12-23.
[3] Doran, A. C., Meller, N., & McNamara, C. A. (2008). Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology, 28(5), 812-819.
[4] Pasterkamp, G., Van Keulen, J. K., & De Kleijn, D. P. V. (2004). Role of Toll‐like receptor 4 in the initiation and progression of atherosclerotic disease. European journal of clinical investigation, 34(5), 328-334.
[5] Li, H., Cybulsky, M. I., Gimbrone Jr, M. A., & Libby, P. (1993). An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arteriosclerosis and thrombosis: a journal of vascular biology, 13(2), 197-204.
[6] Cybulsky, M. I., Iiyama, K., Li, H., Zhu, S., Chen, M., Iiyama, M., ... & Milstone, D. S. (2001). A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. The Journal of clinical investigation, 107(10), 1255-1262.
[7] Johnson, R. C., Chapman, S. M., Dong, Z. M., Ordovas, J. M., Mayadas, T. N., Herz, J., ... & Wagner, D. D. (1997). Absence of P-selectin delays fatty streak formation in mice. The Journal of clinical investigation, 99(5), 1037-1043.
[8] Dong, Z. M., Chapman, S. M., Brown, A. A., Frenette, P. S., Hynes, R. O., & Wagner, D. D. (1998). The combined role of P-and E-selectins in atherosclerosis. The Journal of clinical investigation, 102(1), 145-152.
[9] Collins, T., & Cybulsky, M. I. (2001). NF-κB: pivotal mediator or innocent bystander in atherogenesis?. The Journal of clinical investigation, 107(3), 255-264.
[10] Topper, J. N., & Gimbrone Jr, M. A. (1999). Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype. Molecular medicine today, 5(1), 40-46.
[11] Alexander, R. W. (1995). Hypertension and the pathogenesis of atherosclerosis: oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension, 25(2), 155-161.
[12] Sairanen, T. (2001). Mediators of inflammation in cerebral ischemia: roles of cytokine and cyclooxygenase-2 activation: Expression of interleukin-1beta, tumor necrosis factor-alpha, their receptors, and cyclooxygenase-2 in experimental and clinical brain infarction (Doctoral dissertation, Helsingin yliopisto)
[13] Bobková, D., & Poledne, R. (2003). Lipid metabolism in atherogenesis. Ceskoslovenska Fysiologie, 52(1), 34-41.
[14] Martindale, J. L., & Holbrook, N. J. (2002). Cellular response to oxidative stress: signaling for suicide and survival. Journal of cellular physiology, 192(1), 1-15.
[15] Michel, N. A., Zirlik, A., & Wolf, D. (2017). CD40L and its receptors in atherothrombosis—an update. Frontiers in cardiovascular medicine, 4, 40.
[16] Szmitko, P. E., Wang, C. H., Weisel, R. D., Jeffries, G. A., Anderson, T. J., & Verma, S. (2003). Biomarkers of vascular disease linking inflammation to endothelial activation: Part II. Circulation, 108(17), 2041-2048.
[17] Galis, Z. S., & Khatri, J. J. (2002). Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circulation research, 90(3), 251-262.
[18] Gabriela M.B., Gowtham A., Emely C., James N., Ross C., Enrico N., Roberto I., Mota A. (2024). Platelets in Thrombosis and Atherosclerosis. The American Journal of Pathology, 194 (9), 1608 – 1621.
[19] Theofilis, P., Oikonomou, E., Tsioufis, K., &Tousoulis, D. (2023). The role of macrophages in atherosclerosis: pathophysiologic mechanisms and treatment considerations. International Journal of Molecular Sciences, 24(11), 9568.
[20] Guo Z, Wang L, Liu H, Xie Y. Innate Immune Memory in Monocytes and Macrophages: The Potential Therapeutic Strategies for Atherosclerosis. Cells. 2022; 11(24):4072.
[21] Zhao, Y., Zhang, J., Zhang, W., & Xu, Y. (2021). A myriad of roles of dendritic cells in atherosclerosis. Clinical & Experimental Immunology, 206(1), 12-27.
[22] Chen J, Xiang X, Nie L, Guo X, Zhang F, Wen C, Xia Y, Mao L. (2023). The emerging role of Th1 cells in atherosclerosis and its implications for therapy. Front Immunol. 13:1079668. doi: 10.3389/fimmu.2022.1079668
[23] Chen X, Fang M, Hong J, Guo Y. (2025). Longitudinal Variations in Th and Treg Cells Before and After Percutaneous Coronary Intervention, and Their Intercorrelations and Prognostic Value in Acute Syndrome Patients. Inflammation. 48(1):316-330.
[24] Samson S., Mundkur L., Kakkar V.V. (2012). Immune Response to Lipoproteins in Atherosclerosis. Cholesterol 571846, 12 pages, 2012. https://doi.org/10.1155/2012/571846
[25] Chakrabarti R, Duddu S, Tiwari A, Naidu KT, Sharma P, Chakravorty N, Shukla PC (2023). Natural Killer T cells and the invariant subset promote atherosclerosis: A meta-analysis. Life Sci. 321:121620. doi: 10.1016/j.lfs.2023.121620.
[26] Ebrahimian T., Dierick F., Ta V. et al. (2023). B cell-specific knockout of AID protects against atherosclerosis. Sci Rep 13, 8723. https://doi.org/10.1038/s41598-023-35980-1
[27] Selathurai, A., Deswaerte, V., Kanellakis, P., Tipping, P., Toh, B. H., Bobik, A., & Kyaw, T. (2014). Natural killer (NK) cells augment atherosclerosis by cytotoxic-dependent mechanisms. Cardiovascular research, 102(1), 128-137.
[28] Cavallari, M., Resink, T. J., & De Libero, G. (2011). NK/NKT Cells and Atherosclerosis. In Inflammation and Atherosclerosis (pp. 305-330). Vienna: Springer Vienna.
[29] Ishii, N., Matsumura, T., Kinoshita, H., Fukuda, K., Motoshima, H., Senokuchi, T., ... & Araki, E. (2010). Nifedipine induces peroxisome proliferator-activated receptor-γ activation in macrophages and suppresses the progression of atherosclerosis in apolipoprotein E-deficient mice. Arteriosclerosis, thrombosis, and vascular biology, 30(8), 1598-1605.
[30] Verhaar, M. C., Honing, M. L., van Dam, T., Zwart, M., Koomans, H. A., Kastelein, J. J., & Rabelink, T. J. (1999). Nifedipine improves endothelial function in hypercholesterolemia, independently of an effect on blood pressure or plasma lipids. Cardiovascular research, 42(3), 752-760.
[31] Ueng, K. C., Lin, M. C., Chan, K. C., & Lin, C. S. (2007). Nifedipine gastrointestinal therapeutic system: an overview of its antiatherosclerotic effects. Expert Opinion on Drug Metabolism & Toxicology, 3(5), 769-780.
[32] Yamagishi, S. I., Nakamura, K., Takenaka, K., Matsui, T., & Inoue, H. (2006). Pleiotropic effects of nifedipine on atherosclerosis. Current pharmaceutical design, 12(12), 1543-1547.
[33] Yamagishi, S., & Takeuchi, M. (2005). Atheroprotective properties of nifedipine. International journal of tissue reactions, 27(2), 63-67.
[34] Schlimmer, N., Kratz, M., Böhm, M., &Baumhäkel, M. (2011). Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol‐induced atherosclerosis. British journal of pharmacology, 163(4), 80
[35] Raj, K., Ravinder, G., Simmi, A., Kamlesh, K., &Gansham, M. (2014). Comparative Study of Rosuvastatin as Monotherapy versus Rosuvastatin with Ramipril in Dyslipidemia and Their Effects on Atherosclerosis. American Journal of Medical Sciences, 2(3), 58-63
[36] Osipova, O. A., Kurbakov, N. N., Ovsyannikov, A. G., & Vlasenko, M. A. (2016). Comparative evaluation of the antihypertensive effect of perindopril and losartan potassium in patients with arterial hypertension and stenotic coronary atherosclerosis before revascularization: an open randomized comparative study. Rational Pharmacotherapy in Cardiology, 7(3), 300-305.
[37] Fox, K. (2008). Benefits of perindopril all along the cardiovascular continuum: the level of evidence. European heart journal supplements, 10(suppl_G), G4-G12.
[38] Campbell, J. H., Fennessy, P., & Campbell, G. R. (1992). Effect of Perindopril on the development of atherosclerosis in the cholesterol‐fed rabbit. Clinical and Experimental Pharmacology and Physiology, 19(S19), 13-17.
[39] Fennessy, P. A., Campbell, J. H., & Campbell, G. R. (1994). Perindopril inhibits both the development of atherosclerosis in the cholesterol-fed rabbit and lipoprotein binding to smooth muscle cells in culture. Atherosclerosis, 106(1), 29-41.
[40] Prasad, K., Mantha, S. V., Muir, A. D., & Westcott, N. D. (1998). Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid. Atherosclerosis, 136(2), 367-375.
[41] Prasad, K. (2005). Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed. Atherosclerosis, 179(2), 269-275.
[42] Prasad, K. (2000). Antioxidant activity of secoisolariciresinoldiglucoside-derived metabolites, secoisolariciresinol, enterodiol, and enterolactone. International journal of angiology, 9(04), 220-225.
[43] Prasad, K. (2008). Regression of hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinoldiglucoside isolated from flaxseed. Atherosclerosis, 197(1), 34-42.
[44] Zanwar, A. A., Hegde, M. V., & Bodhankar, S. L. (2014). Flax lignan in the prevention of atherosclerotic cardiovascular diseases. In Polyphenols in human health and disease (pp. 915-921). Academic Press.
[45] Prasad, K. (2007). A study on regression of hypercholesterolemic atherosclerosis in rabbits by flax lignan complex. Journal of cardiovascular pharmacology and therapeutics, 12(4), 304-313.
[46] Schuler, D., Sansone, R., Heiss, C., & Kelm, M. (2013). Is there a Role for Antioxidants in the Treatment of Stable Angina? Current pharmaceutical design, 19(9), 1601-1615.
[47] Cooke, J. P., Singer, A. H., Tsao, P., Zera, P., Rowan, R. A., & Billingham, M. E. (1992). Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. The Journal of clinical investigation, 90(3), 1168-1172.
[48] Singh S, Semwal BC, Kr Upadhaya P. (2019). Pharmacognostic study of Sphaeranthus indicus Linn. A Review. Pharmacog J. 11(6):1376-85.
[49] Srivastava, R. A. K., Mistry, S., & Sharma, S. (2015). A novel anti-inflammatory natural product from Sphaeranthus indicus inhibits expression of VCAM1 and ICAM1, and slows atherosclerosis progression independent of lipid changes. Nutrition & metabolism, 12, 1-16.
[50] Pande, V. V., & Dubey, S. (2009). Antihyperlipidemic activity of Sphaeranthus indicus on atherogenic diet induced hyperlipidemia in rats. International Journal of Green Pharmacy (IJGP), 3(2).
[51] Jiang YH, Jiang LY, Wang YC, Ma DF, Li X. (2020). Quercetin Attenuates Atherosclerosis via Modulating Oxidized LDL-Induced Endothelial Cellular Senescence. Front Pharmacol.11:512. doi: 10.3389/fphar.2020.00512.
[52] Farnaz Ebrahimi, Mohammad Mahdi Ghazimoradi, Ghizal Fatima, Roodabeh Bahramsoltani (2023). Citrus flavonoids and adhesion molecules: Potential role in the management of atherosclerosis. Heliyon 9 (11): e21849 https://doi.org/10.1016/j.heliyon.2023.e21849.
[53] Hung, C., Chan, S., Chu, P., & Tsai, K. (2015). Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation.. Molecular nutrition & food research, 59 10, 1905-17 .
[54] Lu, X. L., Zhao, C. H., Yao, X. L., & Zhang, H. (2017). Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway. Biomedicine & Pharmacotherapy, 85, 658-671.
[55] Lin, W., Wang, W., Wang, D., & Ling, W. (2017). Quercetin protects against atherosclerosis by inhibiting dendritic cell activation.. Molecular nutrition & food research, 61 9.
[56] Bhaskar S, Kumar KS, Krishnan K, Antony H. (2013). Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits. Nutrition 29(1):219-29. doi: 10.1016/j.nut.2012.01.019.
[57] Kondo M, Izawa-Ishizawa Y, Goda M, Hosooka M, Kagimoto Y, Saito N, Matsuoka R, Zamami Y, Chuma M, Yagi K, Takechi K, Tsuneyama K, Ishizawa K. (2020). Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice. Int J Mol Sci. 21(19):7226. doi: 10.3390/ijms21197226.
[58] Garcia, C., & Blesso, C. N. (2021). Antioxidant properties of anthocyanins and their mechanism of action in atherosclerosis. Free Radical Biology and Medicine, 172, 152-166.
[59] Aboonabi, A., & Singh, I. (2015). Chemopreventive role of anthocyanins in atherosclerosis via activation of Nrf2–ARE as an indicator and modulator of redox. Biomedicine & Pharmacotherapy, 72, 30-36.
[60] Wang, D., Wei, X., Yan, X., Jin, T., & Ling, W. (2010). Protocatechuic acid, a metabolite of anthocyanins, inhibits monocyte adhesion and reduces atherosclerosis in apolipoprotein E-deficient mice.. Journal of agricultural and food chemistry, 58 24, 12722
[61] Luo, Y., Fang, J. L., Yuan, K., Jin, S. H., & Guo, Y. (2019). Ameliorative effect of purified anthocyanin from Lycium ruthenicum on atherosclerosis in rats through synergistic modulation of the gut microbiota and NF-κB/SREBP-2 pathways. Journal of Functional Foods, 59, 223-233.
[62] Millar CL, Norris GH, Jiang C, Kry J, Vitols A, Garcia C, Park YK, Lee JY, Blesso CN. (2018). Long-Term Supplementation of Black Elderberries Promotes Hyperlipidemia, but Reduces Liver Inflammation and Improves HDL Function and Atherosclerotic Plaque Stability in Apolipoprotein E-Knockout Mice. Mol Nutr Food Res. 62(23):e1800404. doi: 10.1002/mnfr.201800404.
[63] Sankhari JM, Thounaojam MC, Jadeja RN, Devkar RV, Ramachandran AV (2012). Anthocyanin-rich red cabbage (Brassica oleracea L.) extract attenuates cardiac and hepatic oxidative stress in rats fed an atherogenic diet. J Sci Food Agric 92(8):1688-1693.
[64] Reis JF, Monteiro VV, de Souza Gomes R, do Carmo MM, da Costa GV, Ribera PC, Monteiro MC (2016). Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies. J Transl Med. 14(1):315. doi: 10.1186/s12967-016-1076-5.
[65] Shen J, Li X, Zhang X, Li Z, Abulaiti G, Liu Y, Yao J, Zhang P (2022). Effects of Xinjiang wild cherry plum (Prunus divaricata Ledeb) anthocyanin-rich extract on the plasma metabolome of atherosclerotic apoE-deficient mice fed a high-fat diet. Front Nutr 9:923699. doi: 10.3389/fnut.2022.923699.
[66] Sethumathi, P. P., Uddandrao, V. S., Chandrasekaran, P., Sengottuvelu, S., Tamilmani, P., & Ponmurugan, P. (2023). Biochanin-A Protects Rats from Diabetes-associated Cardiorenal Damage by Attenuating Oxidative Stress through Activation of Nrf-2/HO-1 Pathway. Biosciences Biotechnology Research Asia, 20(2), 499-509.
[67] Yu, X. H., Chen, J. J., Deng, W. Y., Xu, X. D., Liu, Q. X., Shi, M. W., & Ren, K. (2020). Biochanin A mitigates atherosclerosis by inhibiting lipid accumulation and inflammatory response. Oxidative Medicine and Cellular Longevity, 2020, 1-15.
[68] Galindo CL, Khan S, Zhang X, Yeh YS, Liu Z, Razani B (2023). Lipid-laden foam cells in the pathology of atherosclerosis: shedding light on new therapeutic targets. Expert Opin Ther Targets 27(12):1231-1245.
[69] Li M, Ren C (2022). Exploring the protective mechanism of baicalin in treatment of atherosclerosis using endothelial cells deregulation model and network pharmacology. BMC Complement Med Ther 22(1):257. doi: 10.1186/s12906-022-03738-3
[70] Wang Li, Huang Shenyi, Liang Xiaolun, Zhou Junliang, Han Yifan, He Jiangshan, Xu Danping (2024). Immuno-modulatory role of baicalin in atherosclerosis prevention and treatment: current scenario and future directions. Frontiers in Immunology 15 – 2024. doi: 10.3389/fimmu.2024.1377470
[71] Stampfer, M. J., Hennekens, C. H., Manson, J. E., Colditz, G. A., Rosner, B., & Willett, W. C. (1993). Vitamin E consumption and the risk of coronary disease in women. The New England Journal of Medicine, 328(20), 1444–1449.
[72] Egert, S., Bosy-Westphal, A., Seiberl, J., Kürbitz, C., Settler, U., Plachta- Danielzik, S., Müller, M. J. (2009). Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: A double-blinded, placebo-controlled cross-over study. The British Journal of Nutrition, 102(7), 1065–1074.
[73] Basu, A., Sanchez, K., Leyva, M. J., Wu, M., Betts, N. M., Aston, C. E., & Lyons, T. J. (2010). Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome. Journal of the American College of Nutrition, 29(1), 31–40.
[74] Kjær, T. N., Ornstrup, M. J., Poulsen, M. M., Stødkilde-Jørgensen, H., Jessen, N., Jørgensen, J. O. L., … Pedersen, S. B. (2017). No beneficial effects of resveratrol on the metabolic syndrome: A randomized placebo-controlled clinical trial. Journal of Clinical Endocrinology and Metabolism, 102(5), 1642–1651
[75] Regnström, J., Walldius, G., Nilsson, S., Elinder, L. S., Johansson, J., Mölgaard, J., … Nilsson, J. (1996). The effect of probucol on low density lipoprotein oxidation and femoral atherosclerosis. Atherosclerosis, 125(2), 217–229.
[76] Hininger, I. A., Meyer-Wenger, A., Moser, U., Wright, A., Southon, S., Thurnham, D., … Roussel, A. M. (2001). No significant effects of lutein, lycopene or beta-carotene supplementation on biological markers of oxidative stress and LDL oxidizability in healthy adult subjects. Journal of the American College of Nutrition, 20(3), 232–238.
[77] Jeon, S., Kim, T. K., Jeong, S. J., Jung, I. H., Kim, N., Lee, M. N., & Oh, G. T. (2020). Anti-inflammatory actions of soluble Ninjurin-1 ameliorate atherosclerosis. Circulation, 142(18), 1736-1751.
[78] Rothman, A. M., MacFadyen, J., Thuren, T., Webb, A., Harrison, D. G., Guzik, T. J., & Ridker, P. M. (2020). Effects of interleukin-1β inhibition on blood pressure, incident hypertension, and residual inflammatory risk: a secondary analysis of CANTOS. Hypertension, 75(2), 477-482.
[79] Ridker, P. M. (2018). Anti-inflammatory therapy for atherosclerosis: interpreting divergent results from the CANTOS and CIRT clinical trials. Journal of internal medicine, 285(5), 503-509.
[80] Mai W, Liao Y (2020). Targeting IL-1β in the Treatment of Atherosclerosis. Front Immunol. 11:589654. doi: 10.3389/fimmu.2020.589654
[2] Kawai, K., Finn, A. V., & Virmani, R. (2024). Subclinical Atherosclerosis: Part 1: What is it? Can it Be Defined at the Histological Level? Arteriosclerosis, Thrombosis, and Vascular Biology, 44(1), 12-23.
[3] Doran, A. C., Meller, N., & McNamara, C. A. (2008). Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology, 28(5), 812-819.
[4] Pasterkamp, G., Van Keulen, J. K., & De Kleijn, D. P. V. (2004). Role of Toll‐like receptor 4 in the initiation and progression of atherosclerotic disease. European journal of clinical investigation, 34(5), 328-334.
[5] Li, H., Cybulsky, M. I., Gimbrone Jr, M. A., & Libby, P. (1993). An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arteriosclerosis and thrombosis: a journal of vascular biology, 13(2), 197-204.
[6] Cybulsky, M. I., Iiyama, K., Li, H., Zhu, S., Chen, M., Iiyama, M., ... & Milstone, D. S. (2001). A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. The Journal of clinical investigation, 107(10), 1255-1262.
[7] Johnson, R. C., Chapman, S. M., Dong, Z. M., Ordovas, J. M., Mayadas, T. N., Herz, J., ... & Wagner, D. D. (1997). Absence of P-selectin delays fatty streak formation in mice. The Journal of clinical investigation, 99(5), 1037-1043.
[8] Dong, Z. M., Chapman, S. M., Brown, A. A., Frenette, P. S., Hynes, R. O., & Wagner, D. D. (1998). The combined role of P-and E-selectins in atherosclerosis. The Journal of clinical investigation, 102(1), 145-152.
[9] Collins, T., & Cybulsky, M. I. (2001). NF-κB: pivotal mediator or innocent bystander in atherogenesis?. The Journal of clinical investigation, 107(3), 255-264.
[10] Topper, J. N., & Gimbrone Jr, M. A. (1999). Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype. Molecular medicine today, 5(1), 40-46.
[11] Alexander, R. W. (1995). Hypertension and the pathogenesis of atherosclerosis: oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension, 25(2), 155-161.
[12] Sairanen, T. (2001). Mediators of inflammation in cerebral ischemia: roles of cytokine and cyclooxygenase-2 activation: Expression of interleukin-1beta, tumor necrosis factor-alpha, their receptors, and cyclooxygenase-2 in experimental and clinical brain infarction (Doctoral dissertation, Helsingin yliopisto)
[13] Bobková, D., & Poledne, R. (2003). Lipid metabolism in atherogenesis. Ceskoslovenska Fysiologie, 52(1), 34-41.
[14] Martindale, J. L., & Holbrook, N. J. (2002). Cellular response to oxidative stress: signaling for suicide and survival. Journal of cellular physiology, 192(1), 1-15.
[15] Michel, N. A., Zirlik, A., & Wolf, D. (2017). CD40L and its receptors in atherothrombosis—an update. Frontiers in cardiovascular medicine, 4, 40.
[16] Szmitko, P. E., Wang, C. H., Weisel, R. D., Jeffries, G. A., Anderson, T. J., & Verma, S. (2003). Biomarkers of vascular disease linking inflammation to endothelial activation: Part II. Circulation, 108(17), 2041-2048.
[17] Galis, Z. S., & Khatri, J. J. (2002). Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circulation research, 90(3), 251-262.
[18] Gabriela M.B., Gowtham A., Emely C., James N., Ross C., Enrico N., Roberto I., Mota A. (2024). Platelets in Thrombosis and Atherosclerosis. The American Journal of Pathology, 194 (9), 1608 – 1621.
[19] Theofilis, P., Oikonomou, E., Tsioufis, K., &Tousoulis, D. (2023). The role of macrophages in atherosclerosis: pathophysiologic mechanisms and treatment considerations. International Journal of Molecular Sciences, 24(11), 9568.
[20] Guo Z, Wang L, Liu H, Xie Y. Innate Immune Memory in Monocytes and Macrophages: The Potential Therapeutic Strategies for Atherosclerosis. Cells. 2022; 11(24):4072.
[21] Zhao, Y., Zhang, J., Zhang, W., & Xu, Y. (2021). A myriad of roles of dendritic cells in atherosclerosis. Clinical & Experimental Immunology, 206(1), 12-27.
[22] Chen J, Xiang X, Nie L, Guo X, Zhang F, Wen C, Xia Y, Mao L. (2023). The emerging role of Th1 cells in atherosclerosis and its implications for therapy. Front Immunol. 13:1079668. doi: 10.3389/fimmu.2022.1079668
[23] Chen X, Fang M, Hong J, Guo Y. (2025). Longitudinal Variations in Th and Treg Cells Before and After Percutaneous Coronary Intervention, and Their Intercorrelations and Prognostic Value in Acute Syndrome Patients. Inflammation. 48(1):316-330.
[24] Samson S., Mundkur L., Kakkar V.V. (2012). Immune Response to Lipoproteins in Atherosclerosis. Cholesterol 571846, 12 pages, 2012. https://doi.org/10.1155/2012/571846
[25] Chakrabarti R, Duddu S, Tiwari A, Naidu KT, Sharma P, Chakravorty N, Shukla PC (2023). Natural Killer T cells and the invariant subset promote atherosclerosis: A meta-analysis. Life Sci. 321:121620. doi: 10.1016/j.lfs.2023.121620.
[26] Ebrahimian T., Dierick F., Ta V. et al. (2023). B cell-specific knockout of AID protects against atherosclerosis. Sci Rep 13, 8723. https://doi.org/10.1038/s41598-023-35980-1
[27] Selathurai, A., Deswaerte, V., Kanellakis, P., Tipping, P., Toh, B. H., Bobik, A., & Kyaw, T. (2014). Natural killer (NK) cells augment atherosclerosis by cytotoxic-dependent mechanisms. Cardiovascular research, 102(1), 128-137.
[28] Cavallari, M., Resink, T. J., & De Libero, G. (2011). NK/NKT Cells and Atherosclerosis. In Inflammation and Atherosclerosis (pp. 305-330). Vienna: Springer Vienna.
[29] Ishii, N., Matsumura, T., Kinoshita, H., Fukuda, K., Motoshima, H., Senokuchi, T., ... & Araki, E. (2010). Nifedipine induces peroxisome proliferator-activated receptor-γ activation in macrophages and suppresses the progression of atherosclerosis in apolipoprotein E-deficient mice. Arteriosclerosis, thrombosis, and vascular biology, 30(8), 1598-1605.
[30] Verhaar, M. C., Honing, M. L., van Dam, T., Zwart, M., Koomans, H. A., Kastelein, J. J., & Rabelink, T. J. (1999). Nifedipine improves endothelial function in hypercholesterolemia, independently of an effect on blood pressure or plasma lipids. Cardiovascular research, 42(3), 752-760.
[31] Ueng, K. C., Lin, M. C., Chan, K. C., & Lin, C. S. (2007). Nifedipine gastrointestinal therapeutic system: an overview of its antiatherosclerotic effects. Expert Opinion on Drug Metabolism & Toxicology, 3(5), 769-780.
[32] Yamagishi, S. I., Nakamura, K., Takenaka, K., Matsui, T., & Inoue, H. (2006). Pleiotropic effects of nifedipine on atherosclerosis. Current pharmaceutical design, 12(12), 1543-1547.
[33] Yamagishi, S., & Takeuchi, M. (2005). Atheroprotective properties of nifedipine. International journal of tissue reactions, 27(2), 63-67.
[34] Schlimmer, N., Kratz, M., Böhm, M., &Baumhäkel, M. (2011). Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol‐induced atherosclerosis. British journal of pharmacology, 163(4), 80
[35] Raj, K., Ravinder, G., Simmi, A., Kamlesh, K., &Gansham, M. (2014). Comparative Study of Rosuvastatin as Monotherapy versus Rosuvastatin with Ramipril in Dyslipidemia and Their Effects on Atherosclerosis. American Journal of Medical Sciences, 2(3), 58-63
[36] Osipova, O. A., Kurbakov, N. N., Ovsyannikov, A. G., & Vlasenko, M. A. (2016). Comparative evaluation of the antihypertensive effect of perindopril and losartan potassium in patients with arterial hypertension and stenotic coronary atherosclerosis before revascularization: an open randomized comparative study. Rational Pharmacotherapy in Cardiology, 7(3), 300-305.
[37] Fox, K. (2008). Benefits of perindopril all along the cardiovascular continuum: the level of evidence. European heart journal supplements, 10(suppl_G), G4-G12.
[38] Campbell, J. H., Fennessy, P., & Campbell, G. R. (1992). Effect of Perindopril on the development of atherosclerosis in the cholesterol‐fed rabbit. Clinical and Experimental Pharmacology and Physiology, 19(S19), 13-17.
[39] Fennessy, P. A., Campbell, J. H., & Campbell, G. R. (1994). Perindopril inhibits both the development of atherosclerosis in the cholesterol-fed rabbit and lipoprotein binding to smooth muscle cells in culture. Atherosclerosis, 106(1), 29-41.
[40] Prasad, K., Mantha, S. V., Muir, A. D., & Westcott, N. D. (1998). Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid. Atherosclerosis, 136(2), 367-375.
[41] Prasad, K. (2005). Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed. Atherosclerosis, 179(2), 269-275.
[42] Prasad, K. (2000). Antioxidant activity of secoisolariciresinoldiglucoside-derived metabolites, secoisolariciresinol, enterodiol, and enterolactone. International journal of angiology, 9(04), 220-225.
[43] Prasad, K. (2008). Regression of hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinoldiglucoside isolated from flaxseed. Atherosclerosis, 197(1), 34-42.
[44] Zanwar, A. A., Hegde, M. V., & Bodhankar, S. L. (2014). Flax lignan in the prevention of atherosclerotic cardiovascular diseases. In Polyphenols in human health and disease (pp. 915-921). Academic Press.
[45] Prasad, K. (2007). A study on regression of hypercholesterolemic atherosclerosis in rabbits by flax lignan complex. Journal of cardiovascular pharmacology and therapeutics, 12(4), 304-313.
[46] Schuler, D., Sansone, R., Heiss, C., & Kelm, M. (2013). Is there a Role for Antioxidants in the Treatment of Stable Angina? Current pharmaceutical design, 19(9), 1601-1615.
[47] Cooke, J. P., Singer, A. H., Tsao, P., Zera, P., Rowan, R. A., & Billingham, M. E. (1992). Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. The Journal of clinical investigation, 90(3), 1168-1172.
[48] Singh S, Semwal BC, Kr Upadhaya P. (2019). Pharmacognostic study of Sphaeranthus indicus Linn. A Review. Pharmacog J. 11(6):1376-85.
[49] Srivastava, R. A. K., Mistry, S., & Sharma, S. (2015). A novel anti-inflammatory natural product from Sphaeranthus indicus inhibits expression of VCAM1 and ICAM1, and slows atherosclerosis progression independent of lipid changes. Nutrition & metabolism, 12, 1-16.
[50] Pande, V. V., & Dubey, S. (2009). Antihyperlipidemic activity of Sphaeranthus indicus on atherogenic diet induced hyperlipidemia in rats. International Journal of Green Pharmacy (IJGP), 3(2).
[51] Jiang YH, Jiang LY, Wang YC, Ma DF, Li X. (2020). Quercetin Attenuates Atherosclerosis via Modulating Oxidized LDL-Induced Endothelial Cellular Senescence. Front Pharmacol.11:512. doi: 10.3389/fphar.2020.00512.
[52] Farnaz Ebrahimi, Mohammad Mahdi Ghazimoradi, Ghizal Fatima, Roodabeh Bahramsoltani (2023). Citrus flavonoids and adhesion molecules: Potential role in the management of atherosclerosis. Heliyon 9 (11): e21849 https://doi.org/10.1016/j.heliyon.2023.e21849.
[53] Hung, C., Chan, S., Chu, P., & Tsai, K. (2015). Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation.. Molecular nutrition & food research, 59 10, 1905-17 .
[54] Lu, X. L., Zhao, C. H., Yao, X. L., & Zhang, H. (2017). Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway. Biomedicine & Pharmacotherapy, 85, 658-671.
[55] Lin, W., Wang, W., Wang, D., & Ling, W. (2017). Quercetin protects against atherosclerosis by inhibiting dendritic cell activation.. Molecular nutrition & food research, 61 9.
[56] Bhaskar S, Kumar KS, Krishnan K, Antony H. (2013). Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits. Nutrition 29(1):219-29. doi: 10.1016/j.nut.2012.01.019.
[57] Kondo M, Izawa-Ishizawa Y, Goda M, Hosooka M, Kagimoto Y, Saito N, Matsuoka R, Zamami Y, Chuma M, Yagi K, Takechi K, Tsuneyama K, Ishizawa K. (2020). Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice. Int J Mol Sci. 21(19):7226. doi: 10.3390/ijms21197226.
[58] Garcia, C., & Blesso, C. N. (2021). Antioxidant properties of anthocyanins and their mechanism of action in atherosclerosis. Free Radical Biology and Medicine, 172, 152-166.
[59] Aboonabi, A., & Singh, I. (2015). Chemopreventive role of anthocyanins in atherosclerosis via activation of Nrf2–ARE as an indicator and modulator of redox. Biomedicine & Pharmacotherapy, 72, 30-36.
[60] Wang, D., Wei, X., Yan, X., Jin, T., & Ling, W. (2010). Protocatechuic acid, a metabolite of anthocyanins, inhibits monocyte adhesion and reduces atherosclerosis in apolipoprotein E-deficient mice.. Journal of agricultural and food chemistry, 58 24, 12722
[61] Luo, Y., Fang, J. L., Yuan, K., Jin, S. H., & Guo, Y. (2019). Ameliorative effect of purified anthocyanin from Lycium ruthenicum on atherosclerosis in rats through synergistic modulation of the gut microbiota and NF-κB/SREBP-2 pathways. Journal of Functional Foods, 59, 223-233.
[62] Millar CL, Norris GH, Jiang C, Kry J, Vitols A, Garcia C, Park YK, Lee JY, Blesso CN. (2018). Long-Term Supplementation of Black Elderberries Promotes Hyperlipidemia, but Reduces Liver Inflammation and Improves HDL Function and Atherosclerotic Plaque Stability in Apolipoprotein E-Knockout Mice. Mol Nutr Food Res. 62(23):e1800404. doi: 10.1002/mnfr.201800404.
[63] Sankhari JM, Thounaojam MC, Jadeja RN, Devkar RV, Ramachandran AV (2012). Anthocyanin-rich red cabbage (Brassica oleracea L.) extract attenuates cardiac and hepatic oxidative stress in rats fed an atherogenic diet. J Sci Food Agric 92(8):1688-1693.
[64] Reis JF, Monteiro VV, de Souza Gomes R, do Carmo MM, da Costa GV, Ribera PC, Monteiro MC (2016). Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies. J Transl Med. 14(1):315. doi: 10.1186/s12967-016-1076-5.
[65] Shen J, Li X, Zhang X, Li Z, Abulaiti G, Liu Y, Yao J, Zhang P (2022). Effects of Xinjiang wild cherry plum (Prunus divaricata Ledeb) anthocyanin-rich extract on the plasma metabolome of atherosclerotic apoE-deficient mice fed a high-fat diet. Front Nutr 9:923699. doi: 10.3389/fnut.2022.923699.
[66] Sethumathi, P. P., Uddandrao, V. S., Chandrasekaran, P., Sengottuvelu, S., Tamilmani, P., & Ponmurugan, P. (2023). Biochanin-A Protects Rats from Diabetes-associated Cardiorenal Damage by Attenuating Oxidative Stress through Activation of Nrf-2/HO-1 Pathway. Biosciences Biotechnology Research Asia, 20(2), 499-509.
[67] Yu, X. H., Chen, J. J., Deng, W. Y., Xu, X. D., Liu, Q. X., Shi, M. W., & Ren, K. (2020). Biochanin A mitigates atherosclerosis by inhibiting lipid accumulation and inflammatory response. Oxidative Medicine and Cellular Longevity, 2020, 1-15.
[68] Galindo CL, Khan S, Zhang X, Yeh YS, Liu Z, Razani B (2023). Lipid-laden foam cells in the pathology of atherosclerosis: shedding light on new therapeutic targets. Expert Opin Ther Targets 27(12):1231-1245.
[69] Li M, Ren C (2022). Exploring the protective mechanism of baicalin in treatment of atherosclerosis using endothelial cells deregulation model and network pharmacology. BMC Complement Med Ther 22(1):257. doi: 10.1186/s12906-022-03738-3
[70] Wang Li, Huang Shenyi, Liang Xiaolun, Zhou Junliang, Han Yifan, He Jiangshan, Xu Danping (2024). Immuno-modulatory role of baicalin in atherosclerosis prevention and treatment: current scenario and future directions. Frontiers in Immunology 15 – 2024. doi: 10.3389/fimmu.2024.1377470
[71] Stampfer, M. J., Hennekens, C. H., Manson, J. E., Colditz, G. A., Rosner, B., & Willett, W. C. (1993). Vitamin E consumption and the risk of coronary disease in women. The New England Journal of Medicine, 328(20), 1444–1449.
[72] Egert, S., Bosy-Westphal, A., Seiberl, J., Kürbitz, C., Settler, U., Plachta- Danielzik, S., Müller, M. J. (2009). Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: A double-blinded, placebo-controlled cross-over study. The British Journal of Nutrition, 102(7), 1065–1074.
[73] Basu, A., Sanchez, K., Leyva, M. J., Wu, M., Betts, N. M., Aston, C. E., & Lyons, T. J. (2010). Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome. Journal of the American College of Nutrition, 29(1), 31–40.
[74] Kjær, T. N., Ornstrup, M. J., Poulsen, M. M., Stødkilde-Jørgensen, H., Jessen, N., Jørgensen, J. O. L., … Pedersen, S. B. (2017). No beneficial effects of resveratrol on the metabolic syndrome: A randomized placebo-controlled clinical trial. Journal of Clinical Endocrinology and Metabolism, 102(5), 1642–1651
[75] Regnström, J., Walldius, G., Nilsson, S., Elinder, L. S., Johansson, J., Mölgaard, J., … Nilsson, J. (1996). The effect of probucol on low density lipoprotein oxidation and femoral atherosclerosis. Atherosclerosis, 125(2), 217–229.
[76] Hininger, I. A., Meyer-Wenger, A., Moser, U., Wright, A., Southon, S., Thurnham, D., … Roussel, A. M. (2001). No significant effects of lutein, lycopene or beta-carotene supplementation on biological markers of oxidative stress and LDL oxidizability in healthy adult subjects. Journal of the American College of Nutrition, 20(3), 232–238.
[77] Jeon, S., Kim, T. K., Jeong, S. J., Jung, I. H., Kim, N., Lee, M. N., & Oh, G. T. (2020). Anti-inflammatory actions of soluble Ninjurin-1 ameliorate atherosclerosis. Circulation, 142(18), 1736-1751.
[78] Rothman, A. M., MacFadyen, J., Thuren, T., Webb, A., Harrison, D. G., Guzik, T. J., & Ridker, P. M. (2020). Effects of interleukin-1β inhibition on blood pressure, incident hypertension, and residual inflammatory risk: a secondary analysis of CANTOS. Hypertension, 75(2), 477-482.
[79] Ridker, P. M. (2018). Anti-inflammatory therapy for atherosclerosis: interpreting divergent results from the CANTOS and CIRT clinical trials. Journal of internal medicine, 285(5), 503-509.
[80] Mai W, Liao Y (2020). Targeting IL-1β in the Treatment of Atherosclerosis. Front Immunol. 11:589654. doi: 10.3389/fimmu.2020.589654
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May 25, 2024
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Vishal Kumar Soni, Prateek Singh, & Prashant Kumar Singh. (2024). TARGETING INFLAMMATION IN ATHEROSCLEROSIS: INSIGHTS FROM NATURAL AND CONVENTIONAL THERAPIES. Journal of Population Therapeutics and Clinical Pharmacology, 31(5), 2264-2276. https://doi.org/10.53555/2m3r1196
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Author Biographies
Vishal Kumar Soni
Indira Gandhi National Open University, Regional Centre Rajkot, Gujarat, India.
Prateek Singh
Department of Biochemistry, University of Lucknow, Lucknow, Uttar Pradesh, India.
Prashant Kumar Singh
Department of Biochemistry, University of Lucknow, Lucknow, Uttar Pradesh, India.
How to Cite
Vishal Kumar Soni, Prateek Singh, & Prashant Kumar Singh. (2024). TARGETING INFLAMMATION IN ATHEROSCLEROSIS: INSIGHTS FROM NATURAL AND CONVENTIONAL THERAPIES. Journal of Population Therapeutics and Clinical Pharmacology, 31(5), 2264-2276. https://doi.org/10.53555/2m3r1196