期刊
GENES & DEVELOPMENT
卷 19, 期 13, 页码 1624-1634出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1319405
关键词
VEGF; PLC gamma 1; contractility; heart; zebrafish
资金
- NHLBI NIH HHS [R01 HL049579, 1R01HL63206, 5R01HL49579] Funding Source: Medline
- NIDDK NIH HHS [5R01DK55383] Funding Source: Medline
The strength of the heart beat can accommodate in seconds to changes in blood pressure or flow. The mechanism for such homeostatic adaptation is unknown. We sought the cause of poor contractility in the heart of the embryonic zebrafish with the mutation dead beat. We find through cloning that this is due to a mutation in the phospholipase C gamma 1 (plc gamma 1) gene. In mutant embryos, contractile function can be restored by PLC gamma 1 expression directed selectively to cardiac myocytes. In other situations, PLC gamma 1 is known to transduce the signal from vascular endothelial growth factor (VEGF), and we show here that abrogation of VEGF also interferes with cardiac contractility. Somewhat unexpectedly, FLT-1 is the responsible VEGF receptor. We show that the same system functions in the rat. Blockage of VEGF-PLC gamma 1 signaling decreases calcium transients in rat ventricular cardiomyocytes, whereas VEGF imposes a positive inotropic effect on cardiomyocytes by increasing calcium transients. Thus, the muscle of the heart uses the VEGF-PLC gamma 1 cascade to control the strength of the heart beat. We speculate that this paracrine system may contribute to normal and pathological regulation of cardiac contractility.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据