title: Novel agents to manage dyslipidemias and impact atherosclerosis.
abstract: Strong epidemiological evidence linked elevated levels of low-density lipoprotein cholesterol (LDL-C) to risk of atherosclerotic heart disease. As a consequence, LDL-C lowering has been the main goal of therapy to reduce cardiovascular risk for the past few decades and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have become some of the most commonly prescribed drugs. In spite of the proven efficacy of these drugs, statins reduce cardiovascular events by only 30-40%. Epidemiological analyses clearly indicate that a significant portion of risk is linked to other particles such as low high-density lipoprotein cholesterol (HDL-C), high triglycerides and others. Furthermore, several quantitative coronary angiography studies showing regression of atherosclerosis and reduction in subsequent events utilized a combination of drugs effective on LDL-C as well as other lipoproteins. Hence, several new drugs are being investigated that affect more than the traditional LDL-C pathways. In this article, we review lipoprotein-modifying agents that have either been recently released, or are still in various phases of development. They include agents that reduce LDL-C levels by mechanisms other than HMG-CoA inhibition (such as cholesterol absorption inhibitors, Acyl-CoA cholesterol acyl transferase inhibitors, sterol-regulating binding protein cleavage activating protein ligands, microsomal triglyceride transfer protein inhibitors, LDL-C receptor activators and farnesoid X receptor antagonists) and agents that raise HDL-C cholesterol or improve cholesterol efflux (such as cholesterol ester transfer protein inhibitors, retinoid X receptor selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and estrogen like compounds).
authors.affiliation: Department of Medicine, Tulane University School of Medicine, GA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nachimuthu
authors.forename: P
authors.initials: P
authors.lastname: Raggi
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control*; D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL / Q000097:blood; D050171:Dyslipidemias / Q000188:drug therapy*; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000187:drug effects; D011973:Receptors, LDL / Q000235:genetics; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors
chemical_list: D001647:Bile Acids and Salts; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL; D006023:Glycoproteins; D000960:Hypolipidemic Agents; D011973:Receptors, LDL; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D013186:Farnesyl-Diphosphate Farnesyltransferase