Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
Cardiovasc Res. 2011 Jan 1;89(1):12-9. doi: 10.1093/cvr/cvq272. Epub 2010 Aug 24.
Increased numbers of mast cells have been reported in explanted human hearts with dilated cardiomyopathy and in animal models of experimentally induced hypertension, myocardial infarction, and chronic volume overload secondary to aortocaval fistula and mitral regurgitation. Accordingly, mast cells have been implicated to have a major role in the pathophysiology of these cardiovascular disorders. In vitro studies have verified that mast cell proteases are capable of activating collagenase, gelatinases and stromelysin. Recent results have shown that with chronic ventricular volume overload, there is an elevation in mast cell density, which is associated with a concomitant increase in matrix metalloproteinase (MMP) activity and extracellular matrix degradation. However, the role of the cardiac mast cell is not one dimensional, with evidence from hypertension and cardiac transplantation studies suggesting that they can also assume a pro-fibrotic phenotype in the heart. These adverse events do not occur in mast cell deficient rodents or when cardiac mast cells are pharmacologically prevented from degranulating. This review is focused on the regulation and dual roles of cardiac mast cells in: (i) activating MMPs and causing myocardial fibrillar collagen degradation and (ii) causing fibrosis in the stressed, injured or diseased heart. Moreover, there is strong evidence that premenopausal female cardioprotection may at least partly be due to gender differences in cardiac mast cells. This too will be addressed.
研究发现，肥大细胞在扩张型心肌病的人心肌和实验性诱导的高血压、心肌梗死和慢性容量超负荷动物模型（继发于主动脉-腔静脉瘘和二尖瓣反流）的人心肌中数量增加。因此，肥大细胞被认为在这些心血管疾病的病理生理学中起主要作用。体外研究已经证实，肥大细胞蛋白酶能够激活胶原酶、明胶酶和基质金属蛋白酶。最近的研究结果表明，随着慢性心室容量超负荷，肥大细胞密度升高，这与基质金属蛋白酶（MMP）活性和细胞外基质降解的同时增加相关。然而，心脏肥大细胞的作用不是一维的，高血压和心脏移植研究的证据表明，它们在心脏中也可以表现出促纤维化表型。在缺乏肥大细胞的啮齿动物或当心脏肥大细胞被药理学阻止脱颗粒时，这些不良事件不会发生。本综述重点介绍心脏肥大细胞在以下方面的调节和双重作用：（i）激活 MMP 并导致心肌纤维胶原降解，以及（ii）导致应激、损伤或患病心脏纤维化。此外，有强有力的证据表明，绝经前女性的心脏保护作用至少部分可能归因于心脏肥大细胞的性别差异。这也将被讨论。
