Emerging therapies for raising high-density lipoprotein cholesterol (HDL-C) and augmenting HDL particle functionality.
High-density lipoprotein (HDL) particles are highly complex polymolecular aggregates capable of performing a remarkable range of atheroprotective functions. Considerable research is being performed throughout the world to develop novel pharmacologic approaches to: (1) promote apoprotein A-I and HDL particle biosynthesis; (2) augment capacity for reverse cholesterol transport so as to reduce risk for the development and progression of atherosclerotic disease; and (3) modulate the functionality of HDL particles in order to increase their capacity to antagonize oxidation, inflammation, thrombosis, endothelial dysfunction, insulin resistance, and other processes that participate in arterial wall injury. HDL metabolism and the molecular constitution of HDL particles are highly complex and can change in response to both acute and chronic alterations in the metabolic milieu. To date, some of these interventions have been shown to positively impact rates of coronary artery disease progression. However, none of them have as yet been shown to significantly reduce risk for cardiovascular events. In the next 3-5 years a variety of pharmacologic interventions for modulating HDL metabolism and functionality will be tested in large, randomized, prospective outcomes trials. It is hoped that one or more of these therapeutic approaches will result in the ability to further reduce risk for cardiovascular events once low-density lipoprotein cholesterol and non-HDL-cholesterol targets have been attained.
Department of Internal Medicine and Cardiological Rehabilitation, Medical University of Lodz, Lodz, Poland. Electronic address: mbarylski3@wp.pl.
Marcin
M
Barylski
CGH Medical Center, Sterling, IL 61081, USA; University of Illinois School of Medicine, Peoria, IL, USA. Electronic address: peter.toth@cghmc.com.
Peter P
PP
Toth
Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy. Electronic address: draggana.nikolic@gmail.com.
Dragana
D
Nikolic
Nephrology and Hypertension, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland. Electronic address: maciejbanach@aol.co.uk.
Maciej
M
Banach
Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, Palermo, Italy. Electronic address: manfredi.rizzo@unipa.it.
Manfredi
M
Rizzo
Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy. Electronic address: giuseppe.montalto@unipa.it.
Giuseppe
G
Montalto
D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood* / Q000502:physiology*; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000235:genetics / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D035703:Therapies, Investigational / Q000639:trends; D015854:Up-Regulation
D008076:Cholesterol, HDL
RVX-208; apoA-I mimetic; coronary artery disease; delipidation; endothelial lipase inhibitor; farnesoid X receptor; high-density lipoproteins; liver X receptor; reverse cholesterol transport