Crossing Bridges between Extra- and Intra-Cellular Events in Thoracic Aortic Aneurysms.

Crossing Bridges between Extra- and Intra-Cellular Events in Thoracic Aortic Aneurysms. J Atheroscler Thromb. 2017 Sep 22;: Authors: Yamashiro Y, Yanagisawa H Abstract Thoracic aortic aneurysms (TAAs) are common, life-threatening diseases and are a major cause of mortality and morbidity. Over the past decade, genetic approaches have revealed that 1) activation of the transforming growth factor beta (TGF-β) signaling, 2) alterations in the contractile apparatus of vascular smooth muscle cells (SMCs), and 3) defects in the extracellular matrix (ECM) were responsible for development of TAAs. Most recently, a fourth mechanism has been proposed in that dysfunction of mechanosensing in the aortic wall in response to hemodynamic stress may be a key driver of TAAs. Interestingly, the elastin-contractile unit, which is an anatomical and functional unit connecting extracellular elastic laminae to the intracellular SMC contractile filaments, via cell surface receptors, has been shown to play a critical role in the mechanosensing of SMCs, and many genes identified in TAAs encode for proteins along this continuum. However, it is still debated whether these four pathways converge into a common pathway. Currently, an effective therapeutic strategy based on the underlying mechanism of each type of TAAs has not been established. In this review, we will update the present knowledge on the molecular mechanism of TAAs with a focus on the signaling path...
Source: Journal of Atherosclerosis and Thrombosis - Category: Cardiology Tags: J Atheroscler Thromb Source Type: research