Mechanical Regulation of Cardiac Aging in Model Systems.
Mechanical Regulation of Cardiac Aging in Model Systems.
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DOI：
10.1161/circresaha.116.307472
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发表时间：
2016-05-13
影响因子：
20.1
通讯作者：
Engler AJ
中科院分区：
文献类型：
--
作者：
Sessions AO;Engler AJ
与个人可以根据生活方式进行调整的饮食和锻炼不同，衰老是不可避免的。在正常或“健康”的衰老过程中，心脏会经历广泛的血管、细胞和间质分子变化，导致心脏僵硬、顺应性较差，器官功能普遍下降。虽然这些被认为是“心脏重塑”的分子变化曾经被认为与晚期心血管疾病相伴，但它们也可以在没有临床疾病表现的患者中发现。现在人们普遍认识到，这些与年龄相关的机械变化使心脏容易受到与高血压和动脉粥样硬化等疾病相关的心血管压力的影响。然而，最近的研究旨在区分心脏内随年龄增长而发生的维持收缩功能的初始代偿性变化与与疾病相关的适应不良反应。这项工作确定了改善衰老过程中心脏功能的新目标。从无脊椎动物到脊椎动物模型，我们利用这篇综述来描述心肌细胞及其微环境中发生的生理与病理重塑的一些特征，特别关注肌节、闰盘、肋节和细胞外基质 (ECM) 内发生的机械变化。
Unlike diet and exercise, which individuals can modulate according to their lifestyle, aging is unavoidable. With normal or “healthy” aging, the heart undergoes extensive vascular, cellular, and interstitial molecular changes that result in stiffer less compliant hearts that experience a general decline in organ function. While these molecular changes deemed “cardiac remodeling” were once thought to be concomitant with advanced cardiovascular disease, they can be found in patients without manifestation of clinical disease. It is now mostly acknowledged that these age-related mechanical changes confer vulnerability of the heart to cardiovascular stresses associated with disease such as hypertension and atherosclerosis. However, recent studies have aimed at differentiating the initial compensatory changes that occur within the heart with age to maintain contractile function from the maladaptive responses associated with disease. This work has identified new targets to improve cardiac function during aging. Spanning invertebrate to vertebrate models, we use this review to delineate some hallmarks of physiological vs. pathological remodeling that occur in the cardiomyocyte and its microenvironment, focusing especially on the mechanical changes that occur within the sarcomere, intercalated disc, costamere, and extracellular matrix (ECM).