title: Lipid Metabolism and Emerging Targets for Lipid-Lowering Therapy.
abstract: Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide, and dyslipidemia constitutes a major risk factor for CVD and premature atherosclerosis. Therapies to reduce the plasma levels of atherogenic lipoproteins are well established interventions that decrease CVD risk. However, treatment of dyslipidemia with the most widely used lipid-lowering drugs (ie, statins and ezetimibe) often fails to protect a significant proportion of patients from cardiovascular risk. The development of several novel therapies to treat lipid-related disorders and their associated risks is ongoing and includes the following: (1) reducing plasma levels of atherogenic lipoproteins using proprotein convertase subtilisin/kexin type 9 inhibitors, antisense inhibitors of Apolipoprotein (Apo)(a), microsomal triglyceride transfer protein inhibitors, antisense oligonucleotides of ApoB for inhibiting very low-density lipoprotein production, and inhibitors of angiopoietin-like protein 3 or ApoC-III for triglyceride-rich lipoprotein management upstream of low-density lipoprotein production as well as gene replacement therapy to improve low-density lipoprotein and triglyceride-rich lipoprotein clearance; and (2) emerging therapies that target high-density lipoprotein (HDL) and reverse cholesterol transport using cholesteryl ester transfer protein inhibitors, HDL peptide mimetics, and autologous infusion of pre-β HDLs. Clinical trials of several of these emerging therapies are currently being conducted. Despite the potential efficacy of these new therapies in CVD prevention, their costs might limit their use because of limited reimbursement funds. Therefore, the real challenge facing the next generation of lipid-lowering agents will most likely be accessibility, reflecting a new paradigm that applies to almost all emerging therapies for any disease in the era of precision medicine.
authors.affiliation: Clinical Lipidology and Rare Lipid Disorders Unit, Department of Medicine, Université de Montréal Community Gene Medicine Center, Chicoutimi, Québec, Canada. Electronic address: daniel.gaudet@umontreal.ca.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.affiliation: Institute of Nutrition and Functional Foods, Laval University, Québec City, Québec, Canada.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Drouin-Chartier
authors.affiliation: Institute of Nutrition and Functional Foods, Laval University, Québec City, Québec, Canada; Centre hospitalier universitaire de Québec Research Center, Laval University, Québec City, Québec, Canada. Electronic address: patrick.couture@crchul.ulaval.ca.
authors.forename: Patrick
authors.initials: P
authors.lastname: Couture
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy; D014943:Global Health; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood*; D009017:Morbidity; D057285:Precision Medicine / Q000379:methods*
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids