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Original Articles: Adult Cardiac

αB-Crystallin Improves Murine Cardiac Function and Attenuates Apoptosis in Human Endothelial Cells Exposed to Ischemia-Reperfusion

^a Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California
^b Department of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California
^c Department of Immunology, Stanford University School of Medicine, Stanford, California
^d Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California

Accepted for publication February 23, 2011.

^_* Address correspondence to Dr Fischbein, Department of Cardiothoracic Surgery, Stanford University School of Medicine, 300 Pasteur Dr, CVRB MC 5407, Stanford, CA 94305 (Email: mfischbe{at}stanford.edu).

Background: This study investigates the protective effect of exogenous αB-crystallin (CryAB) on myocardial function after ischemia-reperfusion injury.

Methods: Mice underwent temporary left anterior descending artery occlusion for 30 minutes. Either CryAB (50 µg) or phosphate-buffered saline (100 µL [n = 6, each group]) were injected in the intramyocardial medial and lateral perinfarct zone 15 minutes before reperfusion. Intraperitoneal injections were administered every other day. Left ventricular ejection fraction was evaluated on postoperative day 40 with magnetic resonance imaging. To investigate the effect of CryAB on apoptosis after hypoxia/reoxygenation in vitro, murine atrial cardiomyocytes (HL-1 cells) or human microvascular endothelial cells (HMEC-1) were incubated with either 50 µg CryAB (500 µg /10 mL) or phosphate-buffered saline in a hypoxia chamber for 6, 12, and 24 hours, followed by 30 minutes of reoxygenation at room air. Apoptosis was then assessed by western blot (Bcl-2, free bax, cleaved caspases-3, 9, PARP) and enzyme-linked immunosorbent assay analyses (cytoplasmic histone-associated DNA fragments and caspase-3 activity).

Results: On postoperative day 40, CryAB-treated mice had a 1.8-fold increase in left ventricular ejection fraction versus control mice (27% ± 6% versus 15% ± 4% SD, p < 0.005). In vitro, (1) the HL-1 cells showed no significant difference in apoptotic protein expression, cytoplasmic histone-associated DNA fragments, or caspase-3 activity; (2) the HMEC-1 cells had increased but not significant apoptotic protein expression with, however, a significant decrease in cytoplasmic histone-associated DNA fragments (1.5-fold, p < 0.01) and caspase-3 activity (2.7-fold, p < 0.005).

Conclusions: Exogenous CryAB administration significantly improves cardiac function after ischemia-reperfusion injury, in vivo. The protective anti-apoptotic affects of CryAB may target the endothelial cell.

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