Thymosin beta 4 attenuates microcirculatory and hemodynamic destabilization in 
sepsis

Bongiovanni, Dario; Ziegler, Tilman; D'Almeida, Sascha; Zhang, Tianqiong; Ng, Judy K. M.; Dietzel, Steffen; Hinkel, Rabea; Kupatt, Christian

doi:10.1517/14712598.2015.1006193

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Thymosin beta 4 attenuates microcirculatory and hemodynamic destabilization in sepsis

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Ziegler, Tilman
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Bongiovanni, D., Ziegler, T., D'Almeida, S., Zhang, T., Ng, J. K. M., Dietzel, S., et al. (2015). Thymosin beta 4 attenuates microcirculatory and hemodynamic destabilization in sepsis. EXPERT OPINION ON BIOLOGICAL THERAPY. Special Issue: Proceedings of the Fourth International Symposium on Thymosins in Health and Disease, 15(Suppl. 1), S203-S210. doi:10.1517/14712598.2015.1006193.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0028-4007-D

Abstract

Objective: The actin polymerization regulator Thymosin beta 4 (T beta 4) has been shown to be involved in angiogenesis, wound healing, cell survival and anti-inflammatory responses. We have previously shown that T beta 4 is capable of recruiting pericytes, thus stabilizing the endothelial barrier function. Here, we analyzed whether treatment with T beta 4 is able to reduce the pericytes loss in lipopolysaccharides (LPS)-induced sepsis and to improve the hemodynamic function and survival in C57BL/6 mice. Methods: Fourteen days before LPS injection, the mice were injected with an adeno-associated virus carrying the T beta 4 (rAAV.T beta 4) or LacZ gene (rAAV.LacZ). A sepsis-severity score was assessed, and non-invasive hemodynamic and permeability measurements were performed. Heart and muscle samples were analyzed for PECAM-1(+) capillaries and NG2(+)pericytes. Results: At 36 h, there was a decrease of sepsis severity score in rAAV. T beta 4-treated animals as compared to rAAV.LacZ-treated control. rAAV. T beta 4-treated animals displayed lower perivascular leakage and higher blood pressure compared to control. Of note, the rAAV.T beta 4 group showed a higher pericyte count in heart and peripheral muscle samples. Finally, T beta 4-treatment reduced mortality compared to control. Conclusion: The data indicate a preventive role of T beta 4 in septic hypercirculation and highlight T beta 4 as a potential therapeutic target in severe sepsis.