BACKGROUND: The introduction of cyclosporine (CsA) has led to an improvement in the prognosis of solid organ transplantation. However, drug-induced hypertension and nephrotoxicity, associated with the development of atherosclerosis and coronary heart disease, still worsen the long-term outcome of CsA-treated patients. Whether the CsA-induced myocardial changes are associated with the induction of connective tissue growth factor (CTGF), a recently found polypeptide implicated in extracellular matrix synthesis, is not known. METHODS: Spontaneously hypertensive rats (8-9 weeks old) were treated with CsA (5 mg x kg(-1) x d(-1) subcutaneously) for 6 weeks. The influence of angiotensin-converting enzyme inhibition (enalapril 30 mg x kg(-1) x d(-1) orally) and angiotensin-1 receptor blockade (valsartan 3 and 30 mg x kg(-1) x d(-1) orally) on CsA toxicity was also investigated. Myocardial morphology was examined, and vascular lesions were scored. Localization and the quantitative expression of CTGF, as well as collagen I and collagen III, mRNA were evaluated by in situ hybridization and Northern blot. RESULTS: CsA-induced hypertension and nephrotoxicity were associated with myocardial infarcts and vasculopathy of the coronary arteries. CsA increased myocardial CTGF, collagen I, and collagen III mRNA expressions by 91%, 198%, and 151%, respectively. CTGF mRNA expression colocalized with the myocardial lesions. Blockade of the renin-angiotensin system prevented vascular damage and the CsA-induced CTGF, collagen I, and collagen III mRNA overexpressions in the heart. CONCLUSIONS: CsA increases CTGF, collagen I, and collagen III mRNA expressions in the heart. The induction of CTGF gene is mediated, at least in part, by angiotensin II.
BACKGROUND: The introduction of cyclosporine (CsA) has led to an improvement in the prognosis of solid organ transplantation. However, drug-induced hypertension and nephrotoxicity, associated with the development of atherosclerosis and coronary heart disease, still worsen the long-term outcome of CsA-treated patients. Whether the CsA-induced myocardial changes are associated with the induction of connective tissue growth factor (CTGF), a recently found polypeptide implicated in extracellular matrix synthesis, is not known. METHODS: Spontaneously hypertensiverats (8-9 weeks old) were treated with CsA (5 mg x kg(-1) x d(-1) subcutaneously) for 6 weeks. The influence of angiotensin-converting enzyme inhibition (enalapril 30 mg x kg(-1) x d(-1) orally) and angiotensin-1 receptor blockade (valsartan 3 and 30 mg x kg(-1) x d(-1) orally) on CsAtoxicity was also investigated. Myocardial morphology was examined, and vascular lesions were scored. Localization and the quantitative expression of CTGF, as well as collagen I and collagen III, mRNA were evaluated by in situ hybridization and Northern blot. RESULTS:CsA-induced hypertension and nephrotoxicity were associated with myocardial infarcts and vasculopathy of the coronary arteries. CsA increased myocardial CTGF, collagen I, and collagen III mRNA expressions by 91%, 198%, and 151%, respectively. CTGF mRNA expression colocalized with the myocardial lesions. Blockade of the renin-angiotensin system prevented vascular damage and the CsA-induced CTGF, collagen I, and collagen III mRNA overexpressions in the heart. CONCLUSIONS:CsA increases CTGF, collagen I, and collagen III mRNA expressions in the heart. The induction of CTGF gene is mediated, at least in part, by angiotensin II.
Authors: V Paradis; I Bièche; D Dargère; D Cazals-Hatem; I Laurendeau; V Saada; J Belghiti; A Bezeaud; M Vidaud; P Bedossa; D-C Valla Journal: Gut Date: 2005-09-14 Impact factor: 23.059
Authors: E Martínez-Martínez; M Miana; R Jurado-López; M V Bartolomé; F V Souza Neto; M Salaices; N López-Andrés; V Cachofeiro Journal: Int J Obes (Lond) Date: 2014-03-03 Impact factor: 5.095
Authors: Monica Rupérez; Marta Ruiz-Ortega; Vanesa Esteban; Oscar Lorenzo; Sergio Mezzano; Juan Jose Plaza; Jesús Egido Journal: Am J Pathol Date: 2003-11 Impact factor: 4.307