Rupture of vulnerable atherosclerotic plaques or erosion of fibrous plaques cause thrombotic occlusion of coronary artery, leads to acute myocardial infarction or unstable angina. Both aggregation of platelets and activation of blood coagulation system play central role in thrombus formation. Blood coagulation factors, especially activated factor X and thrombin, are also involved in inflammation via activation of protease-activated receptors (PARs) expressed on vascular cells and inflammatory cells. Administration of rivaroxaban, one of direct oral anticoagulants, to apolipoprotein-E deficient (ApoE-/-) mouse attenuates progression of atherosclerotic plaque with decrease in accumulation of macrophages and expression of inflammatory cytokines. Similarly, deficiency of PAR-2 gene in bone marrow cells of ApoE-/- mouse reduces expression of inflammatory cytokines in macrophages and atherosclerotic lesion progression. A recent clinical study indicated that rivaroxaban is effective in secondary prevention of arteriosclerotic diseases when used in combination with aspirin. This effect is conceivable mainly by inhibition of thrombus formation. However, it would be possible that the anti-atherosclerotic action of rivaroxaban contributes to these favorable effects.
Aortic dissection (AD) is an acute and fatal aortic disease for which pathogenesis is largely unknown. While recent studies have highlighted the importance of IL-6 signaling that governs the destructive inflammatory response involving neutrophils and macrophages, precise disease mechanism remains to be elucidated. We examined the activation of STAT3, a signaling molecule that mediate the function of IL-6, in human AD tissue. STAT3 was activated in infiltrating macrophages and in medial smooth muscle cells. Tissue-specific deletion of SOCS3 gene, a negative regulator of STAT3, was utilized to enhance the STAT3 sensitivity in macrophages or in smooth muscle cells. STAT3 activation in macrophage resulted exaggerated AD by enhancing tissue destructive inflammation in mouse aorta. In contrast, STAT3 activation in smooth muscle cells ameliorated AD by collagen deposition and reinforcement of adventitia. These results indicate the presence of complex intercellular network in AD pathogenesis, of which clarification would lead to the development of better clinical strategies.
Aortic prosthetic graft infection is the most devastating complication in vascular surgery. We report three cases of Dacron graft infection in the thoracic and abdominal aorta reconstructed with in situ replacement with a superficial femoral vein (SFV) graft. One patient who underwent redo partial arch replacement with an SFV graft died of bleeding after coming off cardiopulmonary bypass. The second patient underwent re-replacement of the descending thoracic aorta and the third patient underwent abdominal aorta re-replacement; both patients survived. Graft replacement with the SFV may be reliable as a descending thoracic short graft or abdominal graft.