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Cardiovascular & Hematological Disorders-Drug Targets

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ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

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Review Article

Atherosclerosis Potential Drug Targets: Current Scenario and Future Perspectives

Author(s): Omar Mohammed Ali Saleh Al Qarawani, Palwinder Kaur*, Manish Vyas and Sandeep Sharma

Volume 23, Issue 2, 2023

Published on: 05 October, 2023

Page: [77 - 91] Pages: 15

DOI: 10.2174/011871529X262041230922043156

Price: $65

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Abstract

Background: The global burden of atherosclerosis and its implication to cause coronary heart disease and ischemic cardiac problems is the most prevalent cause of morbidity and hospitalization. In the US, there has been an increase in the number of patients with cardiac problems in the last decade, and still remains the primary cause of death in Europe as well as in the US.

Objectives: Even though therapeutic interventions and early diagnosis the formation of the fatty lesion and its subsequent steps are possible, the therapeutic management of the disease remains questionable when clinical data is observed. There is still scope for proper target identification and biomarker recognition, which can serve as a baseline to develop efficient pharmacological agent and delivery systems so that the disease incidence and prevalence can be controlled. The present article highlights the current pathophysiological state of the disease and emerging strategies that are applied to manage the disease.

Findings: This article gives an insight into the limitations of various conventionally used therapeutic agents for disease treatment. The emerging strategies that could prove efficacious in disease treatment. This article also gives an insight into current discoveries in the field of cellular and molecular biology, such as the genetic role in causing dyslipidemia and the role of immune cells and the role of non-coding small RNA, which can set the future direction to develop therapeutics interventions for atherosclerosis.

Keywords: Atherosclerosis, future strategies, PCSK9 inhibitors, dyslipidemia, plaque formation, therapeutic interventions.

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[1]
Fan, J.; Watanabe, T. Atherosclerosis: Known and unknown. Pathol. Int., 2022, 72(3), 151-160.
[http://dx.doi.org/10.1111/pin.13202] [PMID: 35076127]
[2]
Thim, T.; Hagensen, M.K.; Bentzon, J.F.; Falk, E. From vulnerable plaque to atherothrombosis. J. Intern. Med., 2008, 263(5), 506-516.
[http://dx.doi.org/10.1111/j.1365-2796.2008.01947.x] [PMID: 18410594]
[3]
Falk, E. Pathogenesis of atherosclerosis. J. Am. Coll. Cardiol., 2006, 47(8)(Suppl.), C7-C12.
[http://dx.doi.org/10.1016/j.jacc.2005.09.068] [PMID: 16631513]
[4]
Grønholdt, ML; Dalager-Pedersen, S Falk, E Coronary atherosclerosis: determinants of plaque rupture. Eur Heart J., 1998, 19 Suppl C, c24-9.
[5]
Sakakura, K.; Nakano, M.; Otsuka, F.; Ladich, E.; Kolodgie, F.D.; Virmani, R. Pathophysiology of atherosclerosis plaque progression. Heart Lung Circ., 2013, 22(6), 399-411.
[http://dx.doi.org/10.1016/j.hlc.2013.03.001] [PMID: 23541627]
[6]
Bobryshev, Y.V.; Ivanova, E.A.; Chistiakov, D.A.; Nikiforov, N.G.; Orekhov, A.N. Macrophages and their role in atherosclerosis: pathophysiology and transcriptome analysis. BioMed Res. Int., 2016, 2016, 1-13.
[http://dx.doi.org/10.1155/2016/9582430] [PMID: 27493969]
[7]
Badimon, L.; Vilahur, G. Thrombosis formation on atherosclerotic lesions and plaque rupture. J. Intern. Med., 2014, 276(6), 618-632.
[http://dx.doi.org/10.1111/joim.12296] [PMID: 25156650]
[8]
Malekmohammad, K.; Bezsonov, E.E.; Rafieian-Kopaei, M. Role of lipid accumulation and inflammation in atherosclerosis: focus on molecular and cellular mechanisms. Front. Cardiovasc. Med., 2021, 8707529.
[http://dx.doi.org/10.3389/fcvm.2021.707529] [PMID: 34552965]
[9]
Summerhill, V.I.; Grechko, A.V.; Yet, S-F.; Sobenin, I.A.; Orekhov, A.N. The atherogenic role of circulating modified lipids in atherosclerosis. Int. J. Mol. Sci., 2019, 20(14), 3561.
[http://dx.doi.org/10.3390/ijms20143561] [PMID: 31330845]
[10]
Zhu, Y.; Xian, X.; Wang, Z.; Bi, Y.; Chen, Q.; Han, X.; Tang, D.; Chen, R. Research progress on the relationship between atherosclerosis and inflammation. Biomolecules, 2018, 8(3), 80.
[http://dx.doi.org/10.3390/biom8030080] [PMID: 30142970]
[11]
Guerrini, V.; Gennaro, M.L. Foam cells: One size doesn’t fit all. Trends Immunol., 2019, 40(12), 1163-1179.
[http://dx.doi.org/10.1016/j.it.2019.10.002] [PMID: 31732284]
[12]
Stein, O.; Stein, Y. Smooth muscle cells and atherosclerosis. Curr. Opin. Lipidol., 1995, 6(5), 269-274.
[http://dx.doi.org/10.1097/00041433-199510000-00005] [PMID: 8520848]
[13]
Bennett, M.R.; Sinha, S.; Owens, G.K. Vascular smooth muscle cells in atherosclerosis. Circ. Res., 2016, 118(4), 692-702.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306361] [PMID: 26892967]
[14]
Grootaert, M.O.J.; Bennett, M.R. Vascular smooth muscle cells in atherosclerosis: time for a re-assessment. Cardiovasc. Res., 2021, 117(11), 2326-2339.
[http://dx.doi.org/10.1093/cvr/cvab046] [PMID: 33576407]
[15]
Rahman, M.S.; Woollard, K. Atherosclerosis. Adv. Exp. Med. Biol., 2017, 1003, 121-144.
[http://dx.doi.org/10.1007/978-3-319-57613-8_7] [PMID: 28667557]
[16]
Sharif, H.; Akash, M.S.H.; Rehman, K.; Irshad, K.; Imran, I. Pathophysiology of atherosclerosis: Association of risk factors and treatment strategies using plant‐based bioactive compounds. J. Food Biochem., 2020, 44(11), e13449.
[http://dx.doi.org/10.1111/jfbc.13449] [PMID: 32851658]
[17]
Valdivielso, J.M.; Rodríguez-Puyol, D.; Pascual, J.; Barrios, C.; Bermúdez-López, M.; Sánchez-Niño, M.D.; Pérez-Fernández, M.; Ortiz, A. Atherosclerosis in chronic kidney disease: More, less, or just different? Arterioscler. Thromb. Vasc. Biol., 2019, 39(10), 1938-1966.
[http://dx.doi.org/10.1161/ATVBAHA.119.312705] [PMID: 31412740]
[18]
Herrington, W.; Lacey, B.; Sherliker, P.; Armitage, J.; Lewington, S. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ. Res., 2016, 118(4), 535-546.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.307611] [PMID: 26892956]
[19]
Barquera, S.; Pedroza-Tobías, A.; Medina, C.; Hernández-Barrera, L.; Bibbins-Domingo, K.; Lozano, R.; Moran, A.E. Global overview of the epidemiology of atherosclerotic cardiovascular disease. Arch. Med. Res., 2015, 46(5), 328-338.
[http://dx.doi.org/10.1016/j.arcmed.2015.06.006] [PMID: 26135634]
[20]
Moran, A.E.; Forouzanfar, M.H.; Roth, G.A.; Mensah, G.A.; Ezzati, M.; Flaxman, A.; Murray, C.J.L.; Naghavi, M. The global burden of ischemic heart disease in 1990 and 2010: the Global Burden of Disease 2010 study. Circulation, 2014, 129(14), 1493-1501.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.004046] [PMID: 24573351]
[21]
Moran, A.E.; Tzong, K.Y.; Forouzanfar, M.H.; Roth, G.A.; Mensah, G.A.; Ezzati, M.; Murray, C.J.L.; Naghavi, M. Variations in ischemic heart disease burden by age, country, and income: the Global Burden of Diseases, Injuries, and Risk Factors 2010 study. Glob. Heart, 2014, 9(1), 91-99.
[http://dx.doi.org/10.1016/j.gheart.2013.12.007] [PMID: 24977114]
[22]
Kim, A.S.; Johnston, S.C. Global variation in the relative burden of stroke and ischemic heart disease. Circulation, 2011, 124(3), 314-323.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.018820] [PMID: 21730306]
[23]
Wang, C.; Sun, Y.; Jiang, D.; Wang, C.; Liu, S. Risk‐attributable burden of ischemic heart disease in 137 low‐ and middle‐income countries From 2000 to 2019. J. Am. Heart Assoc., 2021, 10(19), e021024.
[http://dx.doi.org/10.1161/JAHA.121.021024] [PMID: 34585592]
[24]
Visseren, F.L.J. ; Mach, F.; Smulders, Y.M.; Carballo, D.; Koskinas, K.C.; Bäck, M.; Benetos, A.; Biffi, A.; Boavida, J.M.; Capodanno, D.; Cosyns, B.; Crawford, C.; Davos, C.H.; Desormais, I.; Di Angelantonio, E.; Franco, O.H.; Halvorsen, S.; Hobbs, F.D.R.; Hollander, M.; Jankowska, E.A.; Michal, M.; Sacco, S.; Sattar, N.; Tokgozoglu, L.; Tonstad, S.; Tsioufis, K.P.; van Dis, I.; van Gelder, I.C.; Wanner, C.; Williams, B.; De Backer, G.; Regitz-Zagrosek, V.; Aamodt, A.H.; Abdelhamid, M.; Aboyans, V.; Albus, C.; Asteggiano, R.; Bäck, M.; Borger, M.A.; Brotons, C.; Čelutkienė, J.; Cifkova, R.; Cikes, M.; Cosentino, F.; Dagres, N.; De Backer, T.; De Bacquer, D.; Delgado, V.; Den Ruijter, H.; Dendale, P.; Drexel, H.; Falk, V.; Fauchier, L.; Ference, B.A.; Ferrières, J.; Ferrini, M.; Fisher, M.; Fliser, D.; Fras, Z.; Gaita, D.; Giampaoli, S.; Gielen, S.; Graham, I.; Jennings, C.; Jorgensen, T.; Kautzky-Willer, A.; Kavousi, M.; Koenig, W.; Konradi, A.; Kotecha, D.; Landmesser, U.; Lettino, M.; Lewis, B.S.; Linhart, A.; Løchen, M-L.; Makrilakis, K.; Mancia, G.; Marques-Vidal, P.; McEvoy, J.W.; McGreavy, P.; Merkely, B.; Neubeck, L.; Nielsen, J.C.; Perk, J.; Petersen, S.E.; Petronio, A.S.; Piepoli, M.; Pogosova, N.G.; Prescott, E.I.B.; Ray, K.K.; Reiner, Z.; Richter, D.J.; Rydén, L.; Shlyakhto, E.; Sitges, M.; Sousa-Uva, M.; Sudano, I.; Tiberi, M.; Touyz, R.M.; Ungar, A.; Verschuren, W.M.M.; Wiklund, O.; Wood, D.; Zamorano, J.L.; Smulders, Y.M.; Carballo, D.; Koskinas, K.C.; Bäck, M.; Benetos, A.; Biffi, A.; Boavida, J-M.; Capodanno, D.; Cosyns, B.; Crawford, C.A.; Davos, C.H.; Desormais, I.; Di Angelantonio, E.; Franco Duran, O.H.; Halvorsen, S.; Richard Hobbs, F.D.; Hollander, M.; Jankowska, E.A.; Michal, M.; Sacco, S.; Sattar, N.; Tokgozoglu, L.; Tonstad, S.; Tsioufis, K.P.; Dis, I.; van Gelder, I.C.; Wanner, C.; Williams, B. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur. Heart J., 2021, 42(34), 3227-3337.
[http://dx.doi.org/10.1093/eurheartj/ehab484] [PMID: 34458905]
[25]
Cirillo, M.; Argento, F.R.; Attanasio, M.; Becatti, M.; Ladisa, I.; Fiorillo, C.; Coccia, M.E.; Fatini, C. Atherosclerosis and endometriosis: The role of diet and oxidative stress in a gender-specific disorder. Biomedicines, 2023, 11(2), 450.
[http://dx.doi.org/10.3390/biomedicines11020450] [PMID: 36830986]
[26]
Shamaki, G.R.; Markson, F.; Soji-Ayoade, D.; Agwuegbo, C.C.; Bamgbose, M.O.; Tamunoinemi, B.M. Peripheral artery disease: A comprehensive updated review. Curr. Probl. Cardiol., 2022, 47(11), 101082.
[http://dx.doi.org/10.1016/j.cpcardiol.2021.101082] [PMID: 34906615]
[27]
Bourassa, M.G.; Campeau, L.; Lespérance, J.; Solymoss, C. Atherosclerosis after coronary artery bypass surgery: results of recent studies and recommendations regarding prevention. Cardiology, 1986, 73(4-5), 259-268.
[http://dx.doi.org/10.1159/000174019] [PMID: 3530460]
[28]
Virani, S.S.; Smith, S.C., Jr; Stone, N.J.; Grundy, S.M. Secondary prevention for atherosclerotic cardiovascular disease. Circulation, 2020, 141(14), 1121-1123.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044282] [PMID: 32250694]
[29]
Esenwa, C.; Gutierrez, J. Secondary stroke prevention: challenges and solutions. Vasc. Health Risk Manag., 2015, 11, 437-450.
[PMID: 26300647]
[30]
Acosta, S.; Johansson, A.; Drake, I. Diet and lifestyle factors and risk of atherosclerotic cardiovascular disease—a prospective cohort study. Nutrients, 2021, 13(11), 3822.
[http://dx.doi.org/10.3390/nu13113822] [PMID: 34836078]
[31]
Vale, N.; Nordmann, A.J.; Schwartz, G.G.; de Lemos, J.; Colivicchi, F.; den Hartog, F.; Ostadal, P.; Macin, S.M.; Liem, A.H.; Mills, E.; Bhatnagar, N.; Bucher, H.C.; Briel, M. Statins for acute coronary syndrome. Cochrane Database Syst. Rev., 2011, (6), CD006870.
[PMID: 21678362]
[32]
Jourdi, G.; Lordkipanidzé, M.; Philippe, A.; Bachelot-Loza, C.; Gaussem, P. Current and novel antiplatelet therapies for the treatment of cardiovascular diseases. Int. J. Mol. Sci., 2021, 22(23), 13079.
[http://dx.doi.org/10.3390/ijms222313079] [PMID: 34884884]
[33]
Schol-Gelok, S.; van der Hulle, T.; Biedermann, J.S.; van Gelder, T.; Klok, F.A.; van der Pol, L.M.; Versmissen, J.; Huisman, M.V.; Kruip, M.J.H.A. Clinical effects of antiplatelet drugs and statins on D-dimer levels. Eur. J. Clin. Invest., 2018, 48(7), e12944.
[http://dx.doi.org/10.1111/eci.12944] [PMID: 29682728]
[34]
Muneer, K.; Nair, A. Angiotensin-converting enzyme inhibitors and receptor blockers in heart failure and chronic kidney disease - Demystifying controversies. Indian Heart J., 2017, 69(3), 371-374.
[http://dx.doi.org/10.1016/j.ihj.2016.08.007] [PMID: 28648436]
[35]
Wright, J.M.; Musini, V.M.; Gill, R. First-line drugs for hypertension. Cochrane Database Syst. Rev., 2018, 4(4), CD001841.
[PMID: 29667175]
[36]
Zhu, J.; Chen, N.; Zhou, M.; Guo, J.; Zhu, C.; Zhou, J.; Ma, M.; He, L. Calcium channel blockers versus other classes of drugs for hypertension. Cochrane Database Syst. Rev., 2021, 10(10), CD003654.
[PMID: 34657281]
[37]
Bauersachs, J. Heart failure drug treatment: the fantastic four. Eur. Heart J., 2021, 42(6), 681-683.
[http://dx.doi.org/10.1093/eurheartj/ehaa1012] [PMID: 33447845]
[38]
Silverio, A.; Cancro, F.P.; Esposito, L.; Bellino, M.; D’Elia, D.; Verdoia, M.; Vassallo, M.G.; Ciccarelli, M.; Vecchione, C.; Galasso, G.; De Luca, G. Secondary cardiovascular prevention after acute coronary syndrome: emerging risk factors and novel therapeutic targets. J. Clin. Med., 2023, 12(6), 2161.
[http://dx.doi.org/10.3390/jcm12062161] [PMID: 36983163]
[39]
Della Badia, L.A.; Elshourbagy, N.A.; Mousa, S.A. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol. Pharmacol. Ther., 2016, 164, 183-194.
[http://dx.doi.org/10.1016/j.pharmthera.2016.04.011] [PMID: 27133571]
[40]
Valerio, M.G.; Velayati, A.; Jain, D.; Aronow, W.S. Promising new therapies for the treatment of hypercholesterolemia. Expert Opin. Biol. Ther., 2016, 16(5), 609-618.
[http://dx.doi.org/10.1517/14712598.2016.1148136] [PMID: 26822080]
[41]
Sahebkar, A.; Watts, G.F. New LDL-cholesterol lowering therapies: pharmacology, clinical trials, and relevance to acute coronary syndromes. Clin. Ther., 2013, 35(8), 1082-1098.
[http://dx.doi.org/10.1016/j.clinthera.2013.06.019] [PMID: 23932550]
[42]
Zhang, X.; Wang, J.; Colello, J. Zheng, SG Mesenchymal stem cells: A potential promise in treating atherosclerosis?; Preprint, 2018.
[http://dx.doi.org/10.20944/preprints201808.0149.v1]
[43]
Waldmann, E.; Parhofer, K.G. Lipoprotein apheresis to treat elevated lipoprotein (a). J. Lipid Res., 2016, 57(10), 1751-1757.
[http://dx.doi.org/10.1194/jlr.R056549] [PMID: 26889050]
[44]
Joffre, J.; Ait-Oufella, H. Targeting the immune response in atherosclerosis: It’s time for clinical trials. Arch. Cardiovasc. Dis., 2017, 110(12), 643-645.
[http://dx.doi.org/10.1016/j.acvd.2017.08.001]
[45]
Fredman, G.; MacNamara, K.C. Atherosclerosis is a major human killer and non-resolving inflammation is a prime suspect. Cardiovasc. Res., 2021, 117(13), cvab309.
[http://dx.doi.org/10.1093/cvr/cvab309] [PMID: 34609505]
[46]
Libby, P.; Bornfeldt, K.E.; Tall, A.R. Atherosclerosis: Successes, surprises, and future challenges. Circ. Res., 2016, 118(4), 531-534.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.308334]
[47]
Agabiti Rosei, E.; Salvetti, M. Management of hypercholesterolemia, appropriateness of therapeutic approaches and new drugs in patients with high cardiovascular risk. High Blood Press. Cardiovasc. Prev., 2016, 23(3), 217-230.
[48]
Libby, P.; Ridker, P.M.; Hansson, G.K. Progress and challenges in translating the biology of atherosclerosis. Nature, 2011, 473(7347), 317-325.
[http://dx.doi.org/10.1038/nature10146] [PMID: 21593864]
[49]
McFarland, A.J.; Davey, A.K.; Anoopkumar-Dukie, S. Statins reduce lipopolysaccharide-induced cytokine and inflammatory mediator release in an in vitro model of microglial-like cells. Mediators Inflamm., 2017, 2017, 1-10.
[http://dx.doi.org/10.1155/2017/2582745] [PMID: 28546657]
[50]
Iwata, H.; Nagai, R. Novel immune signals and atherosclerosis. Curr. Atheroscler. Rep., 2012, 14(5), 484-490.
[http://dx.doi.org/10.1007/s11883-012-0267-7] [PMID: 22864646]
[51]
Raggi, P.; Genest, J.; Giles, J.T.; Rayner, K.J.; Dwivedi, G.; Beanlands, R.S.; Gupta, M. Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions. Atherosclerosis, 2018, 276, 98-108.
[http://dx.doi.org/10.1016/j.atherosclerosis.2018.07.014] [PMID: 30055326]

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