Novel cardioprotective role of a small heat-shock protein, Hsp20, against ischemia/reperfusion injury

• Published in: Circulation (New York, N.Y.) N.Y.), 2005-04, Vol.111 (14), p.1792-1799
• Main Authors: FAN, Guo-Chang, XIAOPING REN, JIANG QIAN, QUNYING YUAN, NICOLAOU, Persoulla, YANG WANG, JONES, W. Keith, GUOXIANG CHU, KRANIAS, Evangelia G
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive agents; Apoptosis - drug effects; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Cardiovascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Genetic Therapy; Heart - drug effects; Heat-Shock Proteins - administration & dosage; Heat-Shock Proteins - genetics; Heat-Shock Proteins - pharmacology; HSP20 Heat-Shock Proteins; In Vitro Techniques; Medical sciences; Mice; Mice, Transgenic; Myocardial Infarction - prevention & control; Myocardial Ischemia - drug therapy; Pharmacology. Drug treatments; Phosphoproteins - administration & dosage; Phosphoproteins - genetics; Phosphoproteins - pharmacology; Reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; Reperfusion Injury - physiopathology; Vasodilator agents. Cerebral vasodilators
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000160851.41872.C6

Heat-shock proteins (Hsps) have been shown to render cardioprotection from stress-induced injury; however, little is known about the role of another small heat-shock protein, Hsp20, which regulates activities of vasodilation and platelet aggregation, in cardioprotection against ischemia injury. We recently reported that increased expression of Hsp20 in cardiomyocytes was associated with improved contraction and protection against beta-agonist-induced apoptosis. To investigate whether overexpression of Hsp20 exerts protective effects in both ex vivo and in vivo ischemia/reperfusion (I/R) injury, we generated a transgenic (TG) mouse model with cardiac-specific overexpression of Hsp20 (10-fold). TG and wild-type (WT) hearts were then subjected to global no-flow I/R (45 minutes/120 minutes) using the Langendorff preparation. TG hearts exhibited improved recovery of contractile performance over the whole reperfusion period. This improvement was accompanied by a 2-fold decrease in lactate dehydrogenase released from the TG hearts. The extent of infarction and apoptotic cell death was also significantly decreased, which was associated with increased protein ratio of Bcl-2/Bax and reduced caspase-3 activity in TG hearts. Furthermore, in vivo experiments of 30-minute myocardial ischemia, via coronary artery occlusion, followed by 24-hour reperfusion, showed that the infarct region-to-risk region ratio was 8.1+/-1.1% in TG hearts (n=7), compared with 19.5+/-2.1% in WT hearts (n=11, P