Integrin aV as a potential target in aortic aneurysm and dissection

Thoracic aortic aneurysm (TAA) is a perilous disease that can lead to aortic dissection (AD), the pathophysiological mechanisms of which remain largely elusive. To improve our understanding of the molecular mechanism underlying TAA, we conducted a tandem mass tag (TMT)-based proteomics analysis and identified two down-regulated proteins, integrin aV, and integrin aL, in serum samples from patients with type A aortic dissection. We confirmed that integrin aV is extensively expressed in the aortic media, and its expression decreases after dissection, whereas the expression of integrin aL showed no significant alteration. Subsequently, by employing a mouse model of TAA induced by ß-Aminopropionitrile (BAPN), we discovered that the mice treated with integrin aV inhibitors Cilengitide or SB273005 developed dramatically expansive ascending TAA, accompanied by exacerbated disorganization or loss of elastic fibers. Bulk RNA sequencing results further indicated that the treatment with integrin aV inhibitors exacerbates the pro-inflammatory response in mouse TAA development. These data suggest that integrin aV may be a novel target for TAA intervention. However, it also raises concerns about exposure to integrin aV inhibitors, which are conducted in serious cancer clinical trials, may pose a potential risk of developing aortic aneurysm (AA)/AD. Overall design: The ascending TAA tissues of mice fed with BAPN and integrin aV inhibitors Cilengitide or SB273005 were harvested for bulk RNA sequencing.