Blockades of angiotensin and aldosterone reduce osteopontin expression and interstitial fibrosis infiltration in rats with myocardial infarction

• Published in: Chinese medical journal Vol. 121; no. 21; pp. 2192 - 2196
• Main Authors: Zhang, Yu-ling, Zhou, Shu-xian, Lei, Juan, Yuan, Gui-yi, Wang, Jing-feng
• Format: Journal Article
• Language: English
• Published: China Department of Cardiology,Second Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510120,China 05.11.2008
• Subjects: Angiotensins - antagonists & inhibitors; Animals; Fibrosis; Hemodynamics; Male; Mineralocorticoid Receptor Antagonists - pharmacology; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardium - chemistry; Myocardium - pathology; Osteopontin - analysis; Rats; Rats, Sprague-Dawley; 心肌梗塞; 血管紧张素; 醛固酮; osteopontin; renin-angiotensin system; myocardial infarction
• ISSN: 0366-6999; 2542-5641
• DOI: 10.1097/00029330-200811010-00016

Background It has been reported that osteopontin has an important role in cardiac fibrosis and remodeling. However, its direct mechanisms remain unclear. The purpose of this study was to investigate the role of angiotensin and aldosterone blockades in cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted （MI） rats. Methods Fifty SD rats that survived 24 hours after ligating left anterior descending coronary artery were randomly divided into three groups： MI-saline group （n=15, 5 ml/d）, MI-perindopril group （n=18, perindopril 2 mg·kg^-1·d^-1） and MI-spironolacton （n=-17, spironolacton 20 mg·kg^-1·d^-1）. A sham operation group （n=15） was selected as non-infarcted control. At 6 weeks after treatment, hemodynamic pararmeters and left ventricular function were measured with catheterization, interstitial fibrosis infiltration and cardiomyocyte diameters were evaluated histologically. Myocardium osteopontin protein expression level in the non-infarcted myocardium was detected by Western blotting. Results No osteopontin protein was detected in the myocardium of sham-operation rats. High levels of osteopontin protein expression were detected in the MI-saline rats, but the levels were suppressed in the MI-perindopril and MI-spironolacton rats at 6 weeks following MI （P 〈0.01, respectively）. Compared with the sham operation group, all rats in the MI group showed marked interstitial fibrosis infiltration in the non-infarction area, higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter （P 〈0.01, respectively）, and developed significant systolic and diastolic dysfunction as indicated by decreased left ventricular systolic pressure （LVSP） and ±dp/dt, as well as increased left ventricular end-diastolic pressure （LVEDP） （P 〈0.01, respectively）. Angiotensin and aldosterone blockades partly prevented cardiac fibrosis and systolic and diastolic dysfunction （P 〈0.01, respectively）. Conclusion Treatment with angiotensin and aldosterone blockades inhibits expression of osteopontin in the non-infarcted myocardium and prevents cardiac remodeling following MI.