Protective Role of Endothelial Fibulin-4 in Valvulo-Arterial Integrity.

Background Homeostasis of the vessel wall is cooperatively maintained by endothelial cells (ECs), smooth muscle cells, and adventitial fibroblasts. The genetic deletion of fibulin-4 () in smooth muscle cells () leads to the formation of thoracic aortic aneurysms with the disruption of elastic fibers. Although is expressed in the entire vessel wall, its function in ECs and relevance to the maintenance of valvulo-arterial integrity are not fully understood.

Role of PAR1-Egr1 in the Initiation of Thoracic Aortic Aneurysm in Fbln4-Deficient Mice.

Objective: Remodeling of the extracellular matrix plays a vital role in cardiovascular diseases. Using a mouse model of postnatal ascending aortic aneurysms (termed ), we have reported that abnormal mechanosensing led to aneurysm formation in with an upregulation of the mechanosensitive transcription factor, Egr1 (Early growth response 1). However, the role of Egr1 and its upstream regulator(s) in the initiation of aneurysm development and their relationship to an aneurysmal microenvironment are unknown.