TNALP associated calcium phosphate microdeposition contributes to thoracic aortic dissection susceptibility

Aortic dissection is a life-threatening cardiovascular emergency characterized by rapid progression and high mortality. Although medial degeneration is a key pathological feature of aortic dissection, the mechanisms that drive aortic wall instability remain incompletely understood. Aortic calcification is a pathological mineralization process that can alter vascular structure and function, but its role in aortic dissection has received limited attention. Here we show that tissue nonspecific alkaline phosphatase associated calcium phosphate microdeposition is linked to aortic medial degeneration and dissection susceptibility. Human aortic dissection tissues and diseased mouse aortas show increased mineralization together with elevated tissue nonspecific alkaline phosphatase activity. Calcium phosphate deposits promote vascular smooth muscle cell phenotypic switching and inflammatory remodeling, while tissue nonspecific alkaline phosphatase facilitates mineral deposition under permissive conditions. Reducing tissue nonspecific alkaline phosphatase activity or expression attenuates aortic calcium phosphate deposition, medial degeneration and dissection in mice. These findings identify tissue nonspecific alkaline phosphatase associated microdeposition as a mechanism contributing to aortic wall vulnerability.