ABSTRACT
Fragmentation/loss of the structural protein elastin represents the precipitating event translating to aortic expansion and subsequent aneurysm formation. The present study tested the hypothesis that greater protein expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and neointimal growth secondary to a reduction of medial elastin content represent sex-dependent events limiting aortic vessel expansion in females. TIMP-1 protein levels were higher in the ascending aorta of female versus male patients diagnosed with a bicuspid aortic valve (BAV). The latter paradigm was recapitulated in the aorta of adult male and female rats complemented by greater TIMP-2 expression in females. CaCl2 (0.5 M) treatment of the infrarenal aorta of adult male and female rats increased the in situ vessel diameter and expansion was significantly smaller in females despite a comparable reduction of medial elastin content. The preferential appearance of a neointimal region of the CaCl2-treated infrarenal aorta of female rats may explain in part the smaller in situ expansion and neointimal growth correlated positively with the % change of the in situ diameter. Neointimal formation was secondary to a significant increase in the density of medial/neointimal vascular smooth muscle cells (VSMCs) that re-entered the G2-M phase whereas VSMC cell cycle re-entry was attenuated in the CaCl2-treated infrarenal aorta of male rats. Thus, greater TIMP-1 expression in the aorta of female BAV patients may prevent excessive elastin fragmentation and preferential neointimal growth following CaCl2-treatment of the infrarenal aorta of female rats represents a sex-dependent biological event limiting vessel expansion secondary to a significant loss of the structural protein.
ABSTRACT
Background: Thoracic ascending aorta aneurysms (TAA) are an important cause of mortality in adults but are a relatively less studied subject compared to abdominal aortic aneurysms (AAA). The purpose of this review is to explain the main aspects (etiology, pathophysiology, diagnosis) of this disease and to summarize the most recent developments in its management. Methodology: Literature was obtained through online health related search engines (PubMed, MEDLINE) by including the following keywords: ascending aorta aneurysm, thoracic aneurysms, Marfan syndrome, bicuspid aortic valve, familial thoracic syndrome, aortic dissection, aorta imaging and aortic aneurysm guidelines. We included articles dating from 1980 to 2014. Findings: Literature revealed how lethal this disease can be and how simple steps such as follow-up and prophylactic surgery can significantly reduce morbidity and mortality. This review also allowed us to realize the many developments that have been made in recent years in the understanding of pathologic mechanisms of this disease. Conclusion: TAA is a silent disease that needs to be recognized early in its course and followed closely in order to recommend appropriate preventive and prophylactic therapy in a timely manner.