Stephenson Matthew K, Lenihan Sean, Covarrubias Roman, Huttinger Ryan M, Gumina Richard J, Sawyer Douglas B, Galindo Cristi L
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center.
Department of Medicine, Vanderbilt University Medical Center; Division of Cardiovascular Medicine, Vanderbilt University Medical Center.
J Vis Exp. 2016 Jun 14(112):54005. doi: 10.3791/54005.
Fibrosis is a component of all forms of heart disease regardless of etiology, and while much progress has been made in the field of cardiac matrix biology, there are still major gaps related to how the matrix is formed, how physiological and pathological remodeling differ, and most importantly how matrix dynamics might be manipulated to promote healing and inhibit fibrosis. There is currently no treatment option for controlling, preventing, or reversing cardiac fibrosis. Part of the reason is likely the sheer complexity of cardiac scar formation, such as occurs after myocardial infarction to immediately replace dead or dying cardiomyocytes. The extracellular matrix itself participates in remodeling by activating resident cells and also by helping to guide infiltrating cells to the defunct lesion. The matrix is also a storage locker of sorts for matricellular proteins that are crucial to normal matrix turnover, as well as fibrotic signaling. The matrix has additionally been demonstrated to play an electromechanical role in cardiac tissue. Most techniques for assessing fibrosis are not qualitative in nature, but rather provide quantitative results that are useful for comparing two groups but that do not provide information related to the underlying matrix structure. Highlighted here is a technique for visualizing cardiac matrix ultrastructure. Scanning electron microscopy of decellularized heart tissue reveals striking differences in structure that might otherwise be missed using traditional quantitative research methods.
纤维化是所有形式心脏病的一个组成部分,无论其病因如何。虽然心脏基质生物学领域已经取得了很大进展,但在基质如何形成、生理和病理重塑有何不同,以及最重要的是如何操纵基质动态以促进愈合和抑制纤维化方面,仍然存在重大差距。目前尚无控制、预防或逆转心脏纤维化的治疗选择。部分原因可能是心脏瘢痕形成极其复杂,比如在心肌梗死后立即替换死亡或濒死的心肌细胞时就会发生这种情况。细胞外基质本身通过激活驻留细胞以及帮助引导浸润细胞到达坏死病变部位来参与重塑过程。基质还是各种基质细胞蛋白的储存库,这些蛋白对正常的基质周转以及纤维化信号传导至关重要。此外,已经证明基质在心脏组织中发挥着机电作用。大多数评估纤维化的技术本质上并非定性的,而是提供定量结果,这些结果对于比较两组数据很有用,但无法提供与潜在基质结构相关的信息。这里重点介绍一种可视化心脏基质超微结构的技术。对脱细胞心脏组织进行扫描电子显微镜检查,揭示了结构上的显著差异,而使用传统定量研究方法可能会忽略这些差异。