Thymosin beta 4 and cardiac protection: implication in inflammation and fibrosis

Thymosin beta 4 (T beta 4) is a ubiquitous protein with diverse biological functions. The effecter molecules targeted by T beta 4 in cardiac protection remain unknown. We summarize previously published work showing that treatment with T beta 4 in the myocardial infarction setting improves cardiac function by activating Akt phosphorylation, promoting the ILK-Pinch-Parvin complex, and suppressing NF- Kappa B and collagen synthesis. In the presence of Wortmannin, T beta 4 showed minimal cardiac protection. In vitro findings revealed that pretreatment with T beta 4 resulted in reduction of intracellular ROS in the cardiac fibroblasts and was associated with increased expression of antioxidant enzymes, reduction of Bax/Bcl sub(2) ratio, and attenuation of profibrotic genes. Silencing of Cu/Zn-SOD, catalase, and Bcl sub(2) genes abrogated the protective effect of T beta 4. Our findings suggest that T beta 4 improves cardiac function by enhancing Akt and ILK activation and suppressing NF- Kappa B activity and collagen synthesis. Furthermore, T beta 4 selectively upregulates catalase, Cu/Zn-SOD, and Bcl sub(2), thereby protecting cardiac fibroblasts from H sub(2)O sub(2)-induced oxidative damage. Further studies are warranted to elucidate the signaling pathway(s) involved in the cardiac protection afforded by T beta 4.