Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease. Export

@article{citeulike:4115349, abstract = {Innovative pharmacological approaches to raise anti-atherogenic high-density lipoprotein-cholesterol (HDL-C) are currently of considerable interest, particularly in atherogenic dyslipidemias characterized by low levels of HDL-C, such as type 2 diabetes, the metabolic syndrome, and mixed dyslipidemia, but equally among individuals with or at elevated risk for premature cardiovascular disease (CVD). Epidemiological and observational studies first demonstrated that HDL-C was a strong, independent predictor of coronary heart disease (CHD) risk, and suggested that raising HDL-C levels might afford clinical benefit. Accumulating data from clinical trials of pharmacological agents that raise HDL-C levels have supported this concept. In addition to the pivotal role that HDL-C plays in reverse cholesterol transport and cellular cholesterol efflux, HDL particles possess a spectrum of anti-inflammatory, anti-oxidative, anti-apoptotic, anti-thrombotic, vasodilatory and anti-infectious properties, all of which potentially contribute to their atheroprotective nature. Significantly, anti-atherogenic properties of HDL particles are attenuated in common metabolic diseases that are characterized by subnormal HDL-C levels, such as type 2 diabetes and metabolic syndrome. Inhibition of cholesteryl ester transfer protein (CETP), a key player in cholesterol metabolism and transport, constitutes an innovative target for HDL-C raising. In lipid efficacy trials, 2 CETP inhibitors-JTT-705 and torcetrapib-induced marked elevation in HDL-C levels, with torcetrapib displaying greater efficacy. Moreover, both agents attenuate aortic atherosclerosis in cholesterol-fed rabbits. Clinical trial data demonstrating the clinical benefits of these drugs on atherosclerosis and CHD are eagerly awaited.}, author = {Chapman, M. J.}, citeulike-article-id = {4115349}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.pharmthera.2006.02.003}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16574234}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16574234}, doi = {10.1016/j.pharmthera.2006.02.003}, issn = {0163-7258}, journal = {Pharmacology \& therapeutics}, keywords = {atherosclerosis, hdl}, month = {September}, number = {3}, pages = {893--908}, posted-at = {2009-02-28 12:29:55}, priority = {2}, title = {Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease.}, url = {http://dx.doi.org/10.1016/j.pharmthera.2006.02.003}, volume = {111}, year = {2006} }

TY - JOUR ID - citeulike:4115349 L3 - citeulike-article-id:4115349 N2 - Innovative pharmacological approaches to raise anti-atherogenic high-density lipoprotein-cholesterol (HDL-C) are currently of considerable interest, particularly in atherogenic dyslipidemias characterized by low levels of HDL-C, such as type 2 diabetes, the metabolic syndrome, and mixed dyslipidemia, but equally among individuals with or at elevated risk for premature cardiovascular disease (CVD). Epidemiological and observational studies first demonstrated that HDL-C was a strong, independent predictor of coronary heart disease (CHD) risk, and suggested that raising HDL-C levels might afford clinical benefit. Accumulating data from clinical trials of pharmacological agents that raise HDL-C levels have supported this concept. In addition to the pivotal role that HDL-C plays in reverse cholesterol transport and cellular cholesterol efflux, HDL particles possess a spectrum of anti-inflammatory, anti-oxidative, anti-apoptotic, anti-thrombotic, vasodilatory and anti-infectious properties, all of which potentially contribute to their atheroprotective nature. Significantly, anti-atherogenic properties of HDL particles are attenuated in common metabolic diseases that are characterized by subnormal HDL-C levels, such as type 2 diabetes and metabolic syndrome. Inhibition of cholesteryl ester transfer protein (CETP), a key player in cholesterol metabolism and transport, constitutes an innovative target for HDL-C raising. In lipid efficacy trials, 2 CETP inhibitors-JTT-705 and torcetrapib-induced marked elevation in HDL-C levels, with torcetrapib displaying greater efficacy. Moreover, both agents attenuate aortic atherosclerosis in cholesterol-fed rabbits. Clinical trial data demonstrating the clinical benefits of these drugs on atherosclerosis and CHD are eagerly awaited. IS - 3 JF - Pharmacology & therapeutics SN - 0163-7258 EP - 908 TI - Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease. VL - 111 SP - 893 KW - atherosclerosis KW - hdl AU - Chapman, MJ PY - 2006/09// UR - http://dx.doi.org/10.1016/j.pharmthera.2006.02.003 ER -