The fibrin-derived peptide Bβ15–42 protects the myocardium against ischemia-reperfusion injury

Nat. Med. 11, 298-304, (2005)

Speaker: 陳煜恬                                  Date: 2005/05/25 15:00~16:00

Commentator: 林立人 醫師                         Place: Room 601   

 Abstract:

Myocardial infarction is caused by the occlusion of the coronary vessel. In an ischemic condition, myocardium will undergo necrosis, which may result in heart failure and death. To reduce myocardial damage, current interventions aim to reopen the occluded vessel. However, sudden reinitiation of blood flow can cause local inflammation, leading to endothelial and myocardial injury, thereby reducing the benefit of reperfusion.¹ Indeed, inflammatory cells need to migrate across endothelial junctions to reach a specific tissue; many molecules participate in the junction, including vascular endothelial (VE)-cadherin, a cell adhesion molecule expressed on vascular endothelium, that induces platelet migration after binding to fibrin.² It has not yet been explored whether binding of fibrin or its fragments to VE-cadherin has any effect on leukocytes transmigration. The authors found that the fibrin fragment N-terminal disulfide knot (NDSK)-Ⅱ can elicit leukocytes adhesion and transmigrate across human umbilical vein endothelial cells monolayer mediated by VE-cadherin. Another fibrin-derived peptide Bβ15–42 competes with NDSK-Ⅱ binding to VE-cadherin and prevents leukocyte transmigration, thereby reducing myocardial inflammation and scar formation in vivo. Finally, in the fibrinogen knockout mice, due to the absence of NDSK-Ⅱ, the infarct size was smaller than wild type mice, while Bβ15–42 did not show obvious protection. In conclusion, this study indicated that the naturally occurring peptide Bβ15–42 represents a potential candidate for myocardial reperfusion therapy.

References:

1.     Entman, M. L., et al. The inflammatory response in myocardial infarction. Cardiovasc. Res. 53, 31–47 (2002).

2.     Martinez, J., et al. Endothelial cell VE-cadherin functions as a receptor forthe β15–42 sequence of fibrin. J. Biol. Chem. 273, 30719–30728 (1998).

3.     Zacharowski, K., et al. The fibrin-derived peptide Bβ15–42 protects themyocardium against ischemia-reperfusion injury. Nat. Med. 11, 298-304 (2005).