title: L-Carnitine protects against arterial hypertension-related cardiac fibrosis through modulation of PPAR-γ expression.
abstract: Cardiac fibrosis is a pathogenic factor in a variety of cardiovascular diseases and is characterized by an abnormal accumulation of extracellular matrix protein that leads to cardiac dysfunction. l-Carnitine (LC) plays an essential role in the β-oxidation of long-chain fatty acids in lipid metabolism. We have previously demonstrated the beneficial effects of LC in hypertensive rats. The aim of this study was to analyze the effect of LC on arterial hypertension-associated cardiac fibrosis and to explore the mechanisms of LC action. To this end, four groups of rats were used: Wistar (control), rats treated with 400mg/kg/day of LC, rats treated with 25mg/kg/day of l-NAME (to induce hypertension), and rats treated with LC+l-NAME simultaneously. We found an elevation in the myocardial expression of profibrotic factors (TGF-β1 and CTGF), types I and III of collagen, and NADPH oxidase subunits (NOX2 and NOX4), in hypertensive rats when compared with normotensive ones. In addition, an increase in myocardial fibrosis was also found in the l-NAME group. These results were accompanied by a down-regulation of PPAR-γ in the heart of hypertensive animals. When hypertensive rats were treated with LC, all these alterations were reversed. Moreover, a significant negative correlation was observed between myocardial interstitial fibrosis and mRNA expression of PPAR-γ. In conclusion, the reduction of cardiac fibrosis and the down-regulation of NOX2, NOX4, TGF-β1 and CTGF induced by LC might be, at least in part, mediated by an upregulation of PPAR-γ, which leads to a reduction on hypertension-related cardiac fibrosis.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, c/Profesor García González 2, 41012 Sevilla, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Zambrano
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Blanca
authors.forename: María V
authors.initials: MV
authors.lastname: Ruiz-Armenta
authors.forename: José L
authors.initials: JL
authors.lastname: Miguel-Carrasco
authors.forename: Miguel
authors.initials: M
authors.lastname: Arévalo
authors.forename: María J
authors.initials: MJ
authors.lastname: Vázquez
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mate
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Vázquez
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002331:Carnitine / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D005355:Fibrosis; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D024042:Collagen Type I; D024043:Collagen Type II; D008562:Membrane Glycoproteins; D047495:PPAR gamma; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D002331:Carnitine; D019331:NG-Nitroarginine Methyl Ester