Controversy on high density lipoprotein raising therapy
Language: 
English
Abstract: 

Decreased high density lipoproteins (HDL) plasma levels are a recognized independent risk factor for atherosclerotic cardiovascular disease. Attempts were therefore initiated to pharmacologically raise plasma HDL cholesterol, and the most impressive increase was obtained by inhibiting cholesteryl ester transfer protein (CETP) by means of the synthetic compound torcetrapib. Clinical trials were however disappointing, as torcetrapib increased mortality and did not reduce the progression of atherosclerosis. According to some view, it was claimed that CETP inhibition is unfavourable and that development of this class of compounds should be abandoned. Controversy nevertheless stimulated research on HDL structure, heterogeneity and functions which are not limited to reverse cholesterol transport and exert antioxidant and antiinflammatory actions. It could also be demonstrated that the deleterious effects of torcetrapib are compound specific, including its tight binding to CETP on HDL particles, thereby blocking both neutral lipids and phospholipid transfer from HDL to other lipoproteins, and would also exert an off-target effect by increasing plasma sodium and decreasing potasium concentrations (an aldosterone-like effect). As the structure of CETP was elucidated, it became possible to design CETP inhibitors that lack such off-target toxicity and may successfully slow the progression of atherosclerosis. Noteworthy, mice and rats naturally lacking CETP are resistant to diet induced atherosclerosis, while rabbits with high CETP levels are very susceptible. Families with deficient activity and exceptional longevity had also been reported.

Author(s): 
Cucuianu, M.
Bruda?c?, Ioana
Item Type: 
Journal Article
Publication Title: 
Romanian Journal of Internal Medicine = Revue Roumaine De MÈdecine Interne
Journal Abbreviation: 
Rom J Intern Med
Publication Date: 
2010
Publication Year: 
2010
Pages: 
111-116
Volume: 
48
Issue: 
2
ISSN: 
1220-4749
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 21428174

Turabian/Chicago Citation

M. Cucuianu and Ioana Bruda?c?. 2010. "Controversy on high density lipoprotein raising therapy." Romanian Journal of Internal Medicine = Revue Roumaine De MÈdecine Interne 48: 2: 111-116.

Wikipedia Citation

<ref> {{Cite journal | doi = | issn = 1220-4749 | volume = 48 | pages = 111-116 | last = Cucuianu | first = M. | coauthors = Bruda?c?, Ioana | title = Controversy on high density lipoprotein raising therapy | journal = Romanian Journal of Internal Medicine = Revue Roumaine De MÈdecine Interne | date = 2010 | pmid = | pmc = }} </ref>