Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling.
Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling.
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DOI：
10.1016/j.yjmcc.2015.11.005
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发表时间：
2016-04
影响因子：
5
通讯作者：
Trafford AW
中科院分区：
文献类型：
--
作者：
Horn MA;Trafford AW
心血管疾病是世界范围内死亡的主要原因，迫切需要新的治疗策略来治疗这类疾病。患心血管疾病的风险随着年龄的增长而急剧增加，但大多数实验研究都是用年轻的动物进行的。心肌细胞外基质（ECM），主要由纤维性胶原蛋白组成，保持心肌完整性，提供力传递的手段，并支持心肌细胞的几何形状。破坏胶原合成、合成后沉积、翻译后修饰和降解的精细平衡控制可能对心肌功能产生有害影响。现在已经确定老化的心脏以纤维化重构为特征，但其机制尚不完全清楚。此外，使用老年动物模型的研究表明，与疾病相关的间质重构可能与年龄有关。因此，随着针对纤维化重塑的新治疗策略的确定，可能有必要考虑年龄依赖的机制。在这篇综述中，我们讨论了心脏胶原基质的重塑作为年龄的功能，同时强调了年龄依赖性纤维化途径的潜在新介质。衰老与心肌胶原蛋白和心功能的改变有关。胶原蛋白重塑与疾病是年龄相关的。胶原重塑介质可能成为老年人疾病治疗的靶点。
Cardiovascular disease is a leading cause of death worldwide and there is a pressing need for new therapeutic strategies to treat such conditions. The risk of developing cardiovascular disease increases dramatically with age, yet the majority of experimental research is executed using young animals. The cardiac extracellular matrix (ECM), consisting predominantly of fibrillar collagen, preserves myocardial integrity, provides a means of force transmission and supports myocyte geometry. Disruptions to the finely balanced control of collagen synthesis, post-synthetic deposition, post-translational modification and degradation may have detrimental effects on myocardial functionality. It is now well established that the aged heart is characterized by fibrotic remodelling, but the mechanisms responsible for this are incompletely understood. Furthermore, studies using aged animal models suggest that interstitial remodelling with disease may be age-dependent. Thus with the identification of new therapeutic strategies targeting fibrotic remodelling, it may be necessary to consider age-dependent mechanisms. In this review, we discuss remodelling of the cardiac collagen matrix as a function of age, whilst highlighting potential novel mediators of age-dependent fibrotic pathways. Aging is associated with alterations to myocardial collagen and cardiac function. Collagen remodelling with disease is age-dependent. Collagen remodelling mediators may become targets for disease treatment in elderly.