Oral administration of diferuloylmethane (curcumin) suppresses proinflammatory cytokines and destructive connective tissue remodeling in experimental abdominal aortic aneurysms.
Chronic transmural inflammation and proteolytic destruction of medial elastin are key mechanisms in the development of abdominal aortic aneurysms (AAAs). Diferuloylmethane (curcumin) is a major component of the food additive tumeric, which has been shown to have anti-inflammatory properties. To determine if ingestion of curcumin influences aneurysmal degeneration, C57Bl/6 mice underwent transient elastase perfusion of the abdominal aorta to induce the development of AAAs, followed by daily oral gavage with 100 mg/kg curcumin (n = 36) or water alone (n = 31). By 14 days, mice in the control group developed a mean increase in aortic diameter of 162.8 +/- 4.6% along with a dense mononuclear inflammation and destruction of medial elastin. By comparison, the mean increase in aortic diameter in the curcumin-treated group was only 133.2 +/- 5.2% (p < 0.0001). Although aortic wall inflammation was similar between the groups, the structural integrity of medial elastin was significantly greater in curcumin-treated mice. Curcumin-treated mice also exhibited relative decreases in aortic tissue activator protein-1 and nuclear factor kappaB DNA binding activities and significantly lower aortic tissue concentrations of interleukin-1beta (IL-1beta), IL-6, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 (all p < 0.05). These data demonstrate for the first time that oral administration of curcumin can suppress the development of experimental AAAs, along with structural preservation of medial elastin fibers and reduced aortic wall expression of several cytokines, chemokines, and proteinases known to mediate aneurysmal degeneration. The possibility that dietary ingestion of curcumin may have a beneficial effect in degenerative aortic aneurysms warrants further consideration.
Parodi
Federico E
FE
Section of Vascular Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Mao
Dongli
D
Ennis
Terri L
TL
Pagano
Monica B
MB
Thompson
Robert W
RW
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D018932:Chemokine CCL2 / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010196:Pancreatic Elastase; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D010196:Pancreatic Elastase; D020780:Matrix Metalloproteinase 9; D003474:Curcumin