Oral administration of diferuloylmethane (curcumin) suppresses proinflammatory cytokines and destructive connective tissue remodeling in experimental abdominal aortic aneurysms

被引:47
作者
Parodi, Federico E.
Mao, Dongli
Ennis, Terri L.
Pagano, Monica B.
Thompson, Robert W.
机构
[1] Washington Univ, Sch Med, Dept Surg, Vasc Surg Sect, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
关键词
D O I
10.1007/s10016-006-9054-7
中图分类号
R61 [外科手术学];
学科分类号
摘要
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 kappa B DNA binding activities and significantly lower aortic tissue concentrations of interleukin-1 beta (IL-1 beta), 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.
引用
收藏
页码:360 / 368
页数:9
相关论文
共 54 条
[1]  
Aggarwal BB, 2003, ANTICANCER RES, V23, P363
[2]   Current concepts in the pathogenesis of abdominal aortic aneurysm [J].
Ailawadi, G ;
Eliason, JL ;
Upchurch, GR .
JOURNAL OF VASCULAR SURGERY, 2003, 38 (03) :584-588
[3]   Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model [J].
Allaire, E ;
Forough, R ;
Clowes, W ;
Starcher, B ;
Clowes, AW .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (07) :1413-1420
[4]   PHARMACOLOGY OF CURCUMA-LONGA [J].
AMMON, HPT ;
WAHL, MA .
PLANTA MEDICA, 1991, 57 (01) :1-7
[5]   Differential regulation of matrix metalloproteinase activities in abdominal aortic aneurysms [J].
Annabi, B ;
Shédid, D ;
Ghosn, P ;
Kenigsberg, RL ;
Desrosiers, RR ;
Bojanowski, MW ;
Beaulieu, É ;
Nassif, E ;
Moumdjian, R ;
Béliveau, R .
JOURNAL OF VASCULAR SURGERY, 2002, 35 (03) :539-546
[6]   Curcumin is an in vivo inhibitor of angiogenesis [J].
Arbiser, JL ;
Klauber, N ;
Rohan, R ;
van Leeuwen, R ;
Huang, MT ;
Fisher, C ;
Flynn, E ;
Byers, HR .
MOLECULAR MEDICINE, 1998, 4 (06) :376-383
[7]   The matrix metalloproteinase inhibitor BB-94 limits expansion of experimental abdominal aortic aneurysms [J].
Bigatel, DA ;
Elmore, JR ;
Carey, DJ ;
Cizmeci-Smith, G ;
Franklin, DP ;
Youkey, JR .
JOURNAL OF VASCULAR SURGERY, 1999, 29 (01) :130-138
[8]   Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines:: an absolute requirement for transcription factor NF-κB [J].
Bond, M ;
Fabunmi, RP ;
Baker, AH ;
Newby, AC .
FEBS LETTERS, 1998, 435 (01) :29-34
[9]   Inhibition of transcription factor NF-κB reduces matrix metalloproteinase-1,-3 and-9 production by vascular smooth muscle cells [J].
Bond, M ;
Chase, AJ ;
Baker, AH ;
Newby, AC .
CARDIOVASCULAR RESEARCH, 2001, 50 (03) :556-565
[10]   Accelerated enlargement of experimental abdominal aortic aneurysms in a mouse model of chronic cigarette smoke exposure [J].
Buckley, C ;
Wyble, CW ;
Borhani, M ;
Ennis, TL ;
Kobayashi, DK ;
Curci, JA ;
Shapiro, SD ;
Thompson, RW .
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS, 2004, 199 (06) :896-903