Molecular aspects of hypercholesterolemia treatment: current perspectives and hopes.

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.

• Authors: Najmeh Ahangari, Majid Ghayour Mobarhan, Amirhossein Sahebkar, Alireza Pasdar
• Journal: Annals of medicine (Ann Med) Vol. 50 Issue 4 Pg. 303-311 (06 2018) ISSN: 1365-2060 [Electronic] England
• PMID: 29578362 (Publication Type: Journal Article, Review)

Chemical References

• ANGPTL3 protein, human
• Angiopoietin-Like Protein 3
• Angiopoietin-like Proteins
• Anticholesteremic Agents
• Bile Acids and Salts
• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• LDLR protein, human
• MicroRNAs
• PCSK9 Inhibitors
• RNA, Small Interfering
• Receptors, LDL
• Sequestering Agents
• PCSK9 protein, human
• Proprotein Convertase 9
• Ezetimibe

Topics

• Angiopoietin-Like Protein 3
• Angiopoietin-like Proteins (antagonists & inhibitors, genetics, metabolism)
• Anticholesteremic Agents (pharmacology, therapeutic use)
• Atherosclerosis (blood, prevention & control)
• Bile Acids and Salts (antagonists & inhibitors, metabolism)
• Cholesterol, LDL (blood, metabolism)
• Disease Progression
• Ezetimibe (pharmacology, therapeutic use)
• Genetic Therapy (methods)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Hypercholesterolemia (blood, genetics, pathology, therapy)
• Intestinal Absorption (drug effects)
• Intestinal Mucosa (drug effects, metabolism)
• MicroRNAs (genetics, therapeutic use)
• Mutation
• PCSK9 Inhibitors
• Proprotein Convertase 9 (genetics, metabolism)
• RNA, Small Interfering (genetics, therapeutic use)
• Receptors, LDL (genetics, metabolism)
• Sequestering Agents (pharmacology, therapeutic use)