|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2002; 39:1752-1757 © 2002 by the American College of Cardiology Foundation |
* Department of Medicine and Aging, Atherosclerosis and Thrombosis Section, University of Chieti Medical School, Chieti, Italy
Manuscript received October 22, 2001; revised manuscript received February 27, 2002, accepted March 1, 2002.
* Reprint requests and correspondence: Prof. Ettore Porreca, Universita G. D’annunzio, Facolta di Medicina e Chirurgia, Centro Servizi Biomedici (SEBI), Via dei Vestini, 66013, Chieti, Italy.
eporreca{at}unich.it
OBJECTIVES: We sought to determine whether inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase with pravastatin affects transforming growth factor-beta1 (TGF-beta1) circulating levels and its production in the monocytes of hypercholesterolemic patients.
BACKGROUND: Transforming growth factor-beta1 is a multifunctional growth factor/cytokine involved in many physiologic and pathologic processes, such as vascular remodeling and atherogenesis. Statins have been reported to have a modulatory role in cytokine expression in the monocytes of hyperlipidemic patients.
METHODS: We evaluated, in a cross-over study design, plasma TGF-beta1 levels and ex vivo TGF-beta1 production in the monocytes of hypercholesterolemic patients before and after four to six weeks of lipid-lowering treatment with diet or diet plus 40 mg/day of pravastatin. In addition, isolated blood monocytes were subjected to pravastatin treatment and evaluated for TGF-beta1 messenger ribonucleic acid (mRNA) expression and TGF-beta1 in vitro production.
RESULTS: Lipid-lowering treatment significantly decreased total cholesterol and low-density lipoprotein cholesterol plasma levels. Pravastatin, but not a low lipid diet, induced a significant increase in TGF-beta1 plasma levels (from 1.7 ± 0.5 ng/ml to 3.1 ± 1.1 ng/ml, p < 0.001) and in ex vivo monocyte production (from 1.8 ± 0.8 ng/ml to 3.9 ± 1.0 ng/ml, p < 0.001). The increase in TGF-beta1 levels was not related to the changes in the lipid profile observed with pravastatin. An increase of approximately twofold in TGF-beta1 production and in mRNA expression was also observed after in vitro treatment of human monocytes with pravastatin (5 µM). Co-incubation with mevalonate reversed the in vitro effect of pravastatin.
CONCLUSIONS: 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition with pravastatin increases TGF-beta1 plasma levels, as well as monocyte production, in hypercholesterolemic patients. The mevalonate pathway plays a role in the regulation of TGF-beta1 expression in human monocytes. A possible implication in the biologic and clinical effects of statins can be suggested.
| ||||||||||||||||
This article has been cited by other articles:
|
|
 |
|
  N. N. Boushra and M. Muntazar Review article: The role of statins in reducing perioperative cardiac risk: physiologic and clinical perspectives: [Le role des statines dans la reduction du risque cardiaque perioperatoire : perspectives physiologiques et cliniques]. Can J Anesth, November 1, 2006; 53(11): 1126 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Cipollone, M. Fazia, G. Mincione, A. Iezzi, B. Pini, C. Cuccurullo, S. Ucchino, F. Spigonardo, M. Di Nisio, F. Cuccurullo, et al. Increased Expression of Transforming Growth Factor-{beta}1 as a Stabilizing Factor in Human Atherosclerotic Plaques Stroke, October 1, 2004; 35(10): 2253 - 2257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bea, E. Blessing, B. Bennett, M. Levitz, E. P. Wallace, and M. E. Rosenfeld Simvastatin Promotes Atherosclerotic Plaque Stability in ApoE-Deficient Mice Independently of Lipid Lowering Arterioscler. Thromb. Vasc. Biol., November 1, 2002; 22(11): 1832 - 1837. [Abstract] [Full Text] [PDF]
|
|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
