1,721,479 research outputs found
Synthetic HDL as a new treatment for atherosclerosis regression : has the time come?
No full textPlasma high-density lipoprotein cholesterol (HDL-C) has received considerable attention as a potential therapeutic target to further reduce cardiovascular events in the statin era. One therapeutic approach to enhance HDL-mediated atheroprotection involves the use of small, synthetic and orally-active compounds that substantially raise plasma HDL-C levels. However, doubts on the clinical benefit achievable with such treatments have been raised by the premature termination of a large Phase III trial with torcetrapib, the most potent and furthest developed HDL-C raising compound, because of excess mortality in patients receiving the drug. The alternative is the direct administration of synthetic HDL (sHDL), discoidal lipoprotein particles which mimic most, if not all, of the atheroprotective properties of plasma HDL. Short-term treatments with sHDL of different composition caused consistent and remarkable reductions of atheroma volume in patients with acute coronary syndromes (ACS). Although at early stages of drug development, sHDL hold vast promise for plaque stabilization/regression, and cardiovascular event reduction
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No full textRaising HDL cholesterol for cardiovascular disease prevention : is this still feasible?
No full textPlasma high-density lipoprotein cholesterol (HDLC) has received considerable attention as a potential therapeutic target to further reduce cardiovascular risk in the statin era. However, doubts about the clinical benefit achievable with treatments enhancing plasma HDLC levels have been raised by the premature termination of a large phase 3 trial with torcetrapib-the most potent and furthest developed HDLC-raising compound-resulting from excess mortality in patients receiving the drug. The causes of torcetrapib failure are unknown and may be related to the drug's mode of action, off-target toxic effects, or a mixture of both. The failure of torcetrapib does not mean that the concept of targeting HDL in cardiovascular prevention is dead. Other HDLC-raising therapies, which act through disparate molecular mechanisms, are in various stages of preclinical and clinical development. The alternative is the direct administration of synthetic HDL, which has proven activity on atherosclerosis regression in coronary patients
High density lipoprotein and coronary heart disease: insights from mutations leading to low high density lipoprotein
No full textHypoalphalipoproteinemia can result from defects in the genes encoding apolipoprotein A-I, the major protein component of HDL, or enzymes that are critical for the formation/maturation of mature HDL. Recent information contradicts earlier findings, suggesting that most of the affected subjects are at increased risk of developing coronary heart disease, independent of the mutated gene. A possible exception is represented by mutations in the apolipoprotein A-I gene leading to structural variants, that might even exert a protective effect against atherosclerosis
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