Molecular aspects of hypercholesterolemia treatment: current perspectives and hopes. (19th May 2018)

• Record Type: Journal Article
• Authors: Ahangari, Najmeh; Ghayour Mobarhan, Majid; Sahebkar, Amirhossein; Pasdar, Alireza
• Is Part Of: Annals of medicine. Volume 50:Number 4(2018)
• Page Start: 303
• Page End: 311
• Publication Date: 2018-05-19
• Subjects: Hypercholesterolemia -- therapy -- lipid-lowering drugs -- low-density lipoprotein cholesterol; Medicine -- Periodicals; 610
• DOI: 10.1080/07853890.2018.1457795
• Languages: English
• ISSNs: 0785-3890

Abstract

Abstract: Hypercholesterolemia is a pathological condition which has been reported in 39% of the worlds' adult population. We aimed to review molecular aspects of current and novel therapeutic approaches based on low-density lipoprotein cholesterol lowering strategies. Pathogenic mutations in the LDLR, ApoB, PCSK9 and LDLRAP genes cause deficient clearance of circulating low-density lipoprotein cholesterol particles via hepatic LDL receptor. This leads to increased plasma LDL cholesterol levels from birth, which can cause LDL depositions in the arterial walls. Ultimately, it progresses to atherosclerosis and an increased risk of premature cardiovascular diseases. Currently, statins, Ezetimibe, Bile acid sequestrants and PCSK9 inhibitors are the main therapeutic agents for the treatment of hypercholesterolemia. Moreover, novel RNA-based therapy had a strong impact on therapeutic strategies in recent decades. Additional development in understanding of the molecular basis of hypercholesterolemia will provide opportunities for the development of targeted therapy in the near future. Key Messages: The most common genes involved in hypercholesterolemia are LDLR, PCSK9 and ApoB . Pharmacogenetic effects are typically constrained to pathways closely related to the pharmacodynamics and pharmacokinetics. Change in lifestyle and diet along with treatment of the underlying disease and drug therapy are the current therapeutic strategies.