curcumin and Aortic-Aneurysm--Thoracic

Angiogenesis is an important process in the pathogenesis of aortic aneurysm. The aim of the present study was to investigate the angiogenic balance and the expression of vascular endothelial growth factor (VEGF) in thoracic aortic aneurysm (TAA). A previous study demonstrated that curcumin exerts a marked effect on aortic aneurysm development. Therefore, the present study determined whether curcumin is able to modulate angiogenesis and inflammatory signaling in TAA by collecting human TAA samples and establishing a rat TAA model using periaortic application of CaCl2. TAA rats were treated with curcumin or 1% carboxymethyl cellulose and were sacrificed 4 weeks after the operation. All tissue specimens were analyzed by histological staining, immunohistochemistry and western blotting. Human TAA samples exhibited increased neovascularization and VEGF expression when compared with normal aortic walls. In rat tissues, treatment with curcumin resulted in reduced aneurysm size and restored the wavy structure of the elastic lamellae. In addition, curcumin decreased neovascularization and the expression of VEGF. Immunohistochemical analysis indicated that curcumin significantly inhibited infiltration of cluster of differentiation (CD)3+ and CD68+ cells in TAA. Furthermore, curcumin treatment decreased the expression of vascular cell adhesion molecule‑1, intracellular adhesion molecule‑1, monocyte chemoattractant protein‑1 and tumor necrosis factor‑α. Collectively, the results demonstrated that angiogenesis and VEGF expression were increased in the aortic wall in TAA. Treatment with curcumin inhibited TAA development in rats, which was associated with suppression of VEGF expression. In addition, curcumin attenuated inflammatory cell infiltration and suppressed inflammatory factor expression in the periaortic tissue of TAA.

Topics: Aged; Animals; Aortic Aneurysm, Thoracic; Biomarkers; Biopsy; Curcumin; Cytokines; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Inflammation Mediators; Male; Middle Aged; Protective Agents; Rats; Vascular Endothelial Growth Factor A

Recent studies have suggested that c-Jun N-terminal kinase (JNK) plays an important role in the formation of abdominal aortic aneurysms, and that direct blockade of JNK by specific inhibitors can effectively prevent the progression of aortic aneurysms. A study has demonstrated that curcumin can suppress the development of experimental abdominal aortic aneurysms by inhibiting inflammation. We sought to investigate whether curcumin could inhibit JNK pathways and apoptosis in thoracic aortic aneurysms.. We used a rat model of a CaCl₂-induced thoracic aortic aneurysm followed by daily oral gavage with curcumin 100 mg/kg or vehicle alone. After treatment for 4 wk, tissue specimens were obtained for histologic assessments, and tissue composition was evaluated using immunohistochemistry, western blotting, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling.. Curcumin significantly suppressed the CaCl₂-induced expansion of the thoracic aortic diameter and the structural preservation of medial elastin fibers. Most importantly, curcumin treatment significantly inhibited the phosphorylation of JNK and c-Jun, accompanied by less cell apoptosis in thoracic aortic aneurysm tissues. Furthermore, the expression levels of caspase-3 and the Bax/Bcl-2 ratio were significantly decreased in the aortic walls of curcumin-treated rats.. The present study indicates that the beneficial effect of curcumin on degenerative aortic aneurysms is related to the inhibition of JNK and apoptosis in the walls of thoracic aortic aneurysms.

Topics: Animals; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Apoptosis; bcl-2-Associated X Protein; Calcium Chloride; Caspase 3; Curcuma; Curcumin; Disease Models, Animal; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Signaling System; Phosphorylation; Phytotherapy; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar