Matrix Metalloproteinases in Post-Ischemic Heart and in Arteriovenous Fistula

• Main Authors: Chih-Yang Chan, 詹志洋
• Other Authors: 陳朝峰
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/77636578329278912520

博士 === 國立臺灣大學 === 生理學研究所 === 95 === Matrix metalloproteinases (MMPs) are extracellular matrix (ECM)–modifying enzymes that are important in the degradation of ECM components and in many physiologic and pathologic cardiovascular processes. Dysregulation of MMPs activity has also been associated with various vascular diseases. Venous dilatation and wall thickening are part of the maturation of a surgically created arteriovenous fistula (AVF) commonly used for vascular access. However, the underlying mechanism of AVF remodeling and whether it affected by the MMPs remains unknown. We therefore studied if matrix remodeling MMPs may contribute to experimental AVF maturation in rats. The results confirmed our hypothesis that a high blood flow rate in the fistula vein affects the expression of MMPs, resulting in the remodeling or maturation of the AVF. Remodeling is associated with degradation of collagen, with an increase in the collagen I/III ratio. MMPs are upregulated by myocardial ischemia, and this facilitates the apoptosis of cardiomyocytes and contributes to the subsequent cardiac dysfunction and to ventricular dilation of the infarcted hearts. Although recombinant human erythropoietin (rhEpo, EPO) protects the myocardium from ischemia-reperfusion injury (IR), but whether it affects ECM degradation is not known. For this reason, we studied MMPs in the post-ischemic hearts and examined the effect of the Janus kinase 2-Extracelular signal-regulated kinase (Jak2-ERK) pathway, which is triggered by EPO, on the expression of MMPs and collagen in post-ischemic hearts. These observations show that EPO attenuates ECM degradation following IR and this may be the basis of the protection from cell death. Jak2-ERK phosphorylation may be an important signal in this process. MMPs continue to represent an exciting focus for basic science and clinical investigation in cardiovascular disease. Our observations show that matrix remodeling MMPs play roles both in EPO myocardial protection and in peripheral AVF remodeling. It is possible that therapeutic modulation of MMP function may soon be developed and will one day change the practice of cardiovascular treatment.