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Lipid-Lowering Therapies for Atherosclerosis: Statins, Fibrates, Ezetimibe and PCSK9 Monoclonal Antibodies

[ Vol. 28 , Issue. 36 ]

Author(s):

Adel Hajj Ali, Nour Younis, Rola Abdallah, Farah Shaer, Ali Dakroub, Mohammed Akli Ayoub, Rabah Iratni, Hadi Mohamad Yassine, Kazem Zibara, Alexander Orekhov, Ahmed Fawzy El-Yazbi and Ali H. Eid *   Pages 7427 - 7445 ( 19 )

Abstract:


Cardiovascular disease (CVD) remains the primary cause of global morbidity and mortality. CVD includes various life-threatening conditions such as myocardial infarction, stroke and peripheral arterial diseases. In this context, atherosclerosis continues to play the principal role in the pathogenesis of these conditions. Atherosclerosis emanates from a set of modifiable and non-modifiable risk factors that include age, male gender, family history, obesity, smoking, diabetes mellitus and hypertension. Recent evidence classifies atherosclerosis as a latent disease affecting all-sized arteries with a predilection for arterial branching points of decreased or absent blood supply. Atherosclerosis is not only a lipid metabolism disorder, but is also a chronic inflammatory one. This review providesa synoptic discussion of the underlying pathological mechanisms of atherosclerosis andthe currently applied therapeutic interventions. We then discuss the classical lipid-lowering therapies as well as the newly discovered therapies. For the classical therapies, we point out the importance of statins and ezetimibe in reducing plasma cholesterol levels by virtue of their effects on synthesis, reuptake and intestinal absorption of cholesterol. We also discuss the role of fibrates in modulating lipid metabolism and improving the ratio of high-density to low-density density lipoproteins. This study focuseson the more recent molecular and genetic interventions exemplified by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, evinacumab, and microRNA inhibitors. Special attention is also given to clinical trials involving these therapies.

Keywords:

Atherosclerosis, statin, fibrates, ezetimibe, PCSK9 inhibitors, microRNA inhibitors, monoclonal antibodies for atherosclerosis.

Affiliation:

Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Department of Biology, College of Science, United Arab Emirates University, Al-Ain, P.O. Box 17551, Department of Biology, College of Science, United Arab Emirates University, Al-Ain, P.O. Box 17551, Biomedical Research Center, Qatar University, Doha, Biology department, Faculty of Sciences, Lebanese University, Beirut, Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Institute of Human Morphology, 3 Tsyurupa Street, Moscow 117418, Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, P.O. Box 2713



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