Shp shape: FAKs about hypertrophy.
Shp shape: FAKs about hypertrophy.
复制标题
Shp 形状：关于肥大的常见问题。
DOI：
10.1161/circresaha.108.186452
复制
发表时间：
2008
影响因子：
20.1
通讯作者：
Hwa,John
中科院分区：
文献类型：
--
作者：
Martin,KathleenA;Hwa,John
尽管最近在心血管疾病的预防和治疗方面取得了进展，但心力衰竭仍然是西方国家发病率和死亡率的主要原因。心脏肥厚，即心脏重量相对于体重的增加，可能是一种有益的适应性反应，就像运动员的心脏（“生理性肥厚”）一样，但很明显，不同形式的病理性肥厚（由压力或容量过载引起）可以发展为心力衰竭。心脏肥厚，即使在没有明显衰竭的情况下，也具有预后意义。超声心动图确定左心室体积和几何形状增加的高血压患者心血管死亡的风险更高。这一发现导致了对减少肥厚的药物的深入研究。血管紧张素转换酶抑制剂已被证明可以减少肥大，影响重塑，并提高生存率。近年来，我们在剖析不同肥厚表型（包括生理性、同心型或偏心型）的分子信号机制方面取得了进展，但我们目前的理解似乎只反映了心脏重塑复杂调控的冰山一角。仍然存在的一个主要问题是机械（和神经激素）刺激是如何被转导成驱动肥大的分子信号的。最近的一些研究表明，由Ptpn11基因编码的酪氨酸磷酸酶Shp2 （Src同源2结构域蛋白酪氨酸磷酸酶）可能是将机械信号转导到心脏肥大的分子和病理生理表现中的关键参与者。在这一期的Circulation Research中，Marin等人认为Shp2是拉伸诱导的心肌细胞肥大的关键介质。整合素将细胞外基质与细胞内细胞骨架连接起来，酪氨酸激酶局灶黏附激酶（FAK）和Src等蛋白质参与了运动相关信号的转导。FAK与循环拉伸的肥厚反应有关。体内研究也指出，在压力过载引起的心脏肥厚中需要FAK。9,10目前的研究表明，Shp2介导拉伸信号-
Despite recent advances in cardiovascular disease preven-tion and treatment, heart failure remains a major cause of morbidity and mortality in Western countries. Cardiac hypertrophy, an increase in heart weight relative to body weight, can be a beneficial adaptive response, as in the heart of the athlete (“physiological hypertrophy”), but it is clear that distinct forms of pathological hypertrophy (induced by pressure or volume overload) can progress to cardiac failure. 1, 2 Cardiac hypertrophy, even in the absence of overt failure, has prognostic significance. Hypertensive patients with echocardiographically determined increases in left ventricular mass and geometry have a higher risk of cardiovascular death. 3 This finding has led to intensive investigations into drugs that reduce hypertrophy. 4 Angiotensin-converting enzyme inhibitors have been shown to reduce hypertrophy, 4 influence remodeling, 5 and improve survival. 6 In recent years, we have progressed in dissecting the molecular signaling mechanisms underlying distinct hypertrophic phenotypes (including physiological, concentric, or eccentric), but it appears that our present understanding reflects only the tip of the iceberg of the complex regulation of remodeling in the heart. A major question that remains is how mechanical (and neurohormonal) stimuli are transduced into molecular signals that drive hypertrophy.Several recent studies reveal that the tyrosine phosphatase Shp2 (Src homology 2 domain–containing protein tyrosine phosphatase), encoded by the Ptpn11 gene, may be a key player in transducing mechanical signals into the molecular and pathophysiological manifestations of cardiac hypertrophy. In this issue of Circulation Research, Marin et al implicate Shp2 as a critical mediator of stretch-induced cardiomyocyte hypertrophy. 7 Integrins link the extracellular matrix with the intracellular cytoskeleton, and proteins such as the tyrosine kinases focal adhesion kinase (FAK) and Src are involved in transducing motility-associated signals. FAK had been implicated in the hypertrophic response to cyclic stretch. 8 In vivo studies also point to a requirement for FAK in pressure overload–induced cardiac hypertrophy. 9, 10 The present study now reveals that Shp2 mediates stretch signal-
长凳和床边之间的“差距”：扩大还是缩小？
影响因子：
6
作者：
A. Katz
通讯作者：
A. Katz
影响因子：
15.9
作者：
IZUMO, S;LOMPRE, AM;MAHDAVI, V
通讯作者：
MAHDAVI, V
影响因子：
39.2
作者：
KOREN, MJ;DEVEREUX, RB;LARAGH, JH
通讯作者：
LARAGH, JH