Gene transfer of endothelial NO synthase and manganese superoxide dismutase on arterial vascular cell adhesion molecule-1 expression and superoxide production in deoxycorticosterone acetate-salt hypertension

被引:48
作者
Li, LX
Crockett, E
Wang, DH
Galligan, JJ
Fink, GD
Chen, AF [1 ]
机构
[1] Michigan State Univ, Coll Human Med, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA
[2] Michigan State Univ, Coll Human Med, Neurosci Program, E Lansing, MI 48824 USA
[3] Michigan State Univ, Coll Human Med, Dept Surg, E Lansing, MI 48824 USA
[4] Michigan State Univ, Coll Human Med, Dept Med, E Lansing, MI 48824 USA
关键词
endothelial NO synthase; gene transfer; hypertension; superoxide; ascular cell adhesion molecule-1;
D O I
10.1161/hq0202.104124
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Enhanced vascular cell adhesion molecule-1 (VCAM-1) expression directly contributes to vascular dysfunction in hypertension. Decreased NO and/or increased superoxide are causative factors for such an event in the vessel wall. The present study was undertaken to determine whether gene transfer of endothelial NO synthase (eNOS) or manganese superoxide dismutase (MnSOD) affects VCAM-1 levels in arteries from hypertensive rats. Isolated carotid and femoral arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats were transduced for 4 hours with adenoviral vectors encoding eNOS, MnSOD, or beta-galactosidase reporter genes. Recombinant eNOS or MnSOD expression was evident morphologically and quantitatively 24 hours after gene transfer. Immunohistochemistry, ELISA, and Western blot techniques were used to determine VCAM-1 expression and levels. In addition, endogenous eNOS and MnSOD and in situ superoxide levels were analyzed by immunoblotting and fluorescence confocal microscopy, respectively. Arterial VCAM-1 expression was significantly higher in DOCA-salt hypertensive rats than in sham-operated rats; this expression was accompanied by decreased MnSOD but unaltered endogenous eNOS levels. VCAM-1 expression was significantly lower in MnSOD- and eNOS-transduced hypertensive arteries, with a concomitant reduction of superoxide level. These results suggest that gene transfer of MnSOD or eNOS suppresses arterial VCAM-1 expression in DOCA-salt hypertension by reducing the superoxide level.
引用
收藏
页码:249 / 255
页数:7
相关论文
共 42 条
[1]   Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide dismutase restores nitric oxide availability in the SHRSP [J].
Alexander, MY ;
Brosnan, MJ ;
Hamilton, CA ;
Fennell, JP ;
Beattie, EC ;
Jardine, E ;
Heistad, DD ;
Dominiczak, AF .
CARDIOVASCULAR RESEARCH, 2000, 47 (03) :609-617
[2]   Increased endothelium-monocyte interactions in salt-sensitive hypertension: Effect of L-arginine [J].
Artigues, C ;
Richard, V ;
Roussel, C ;
Lallemand, F ;
Henry, JP ;
Thuillez, C .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2000, 35 (03) :468-473
[3]  
Brzezinska AK, 2001, CIRCULATION, V104, P99
[4]   Endothelial dysfunction in cardiovascular diseases - The role of oxidant stress [J].
Cai, H ;
Harrison, DG .
CIRCULATION RESEARCH, 2000, 87 (10) :840-844
[5]   In vivo gene transfer of nitric oxide synthase enhances vasomotor function in carotid arteries from normal and cholesterol-fed rabbits [J].
Channon, KM ;
Qian, HS ;
Neplioueva, V ;
Blazing, MA ;
Olmez, E ;
Shetty, GA ;
Youngblood, SA ;
Pawloski, J ;
McMahon, T ;
Stamler, JS ;
George, SE .
CIRCULATION, 1998, 98 (18) :1905-1911
[6]  
CHEN AF, 2000, NITRIC OXIDE BIOL PA, P5225
[7]   Expression and function of recombinant endothelial nitric oxide synthase gene in canine basilar artery [J].
Chen, AFY ;
OBrien, T ;
Tsutsui, M ;
Kinoshita, H ;
Pompili, VJ ;
Crotty, TB ;
Spector, DJ ;
Katusic, ZS .
CIRCULATION RESEARCH, 1997, 80 (03) :327-335
[8]   Effects of in vivo adventitial expression of recombinant endothelial nitric oxide synthase gene in cerebral arteries [J].
Chen, AFY ;
Jiang, SW ;
Crotty, TB ;
Tsutsui, M ;
Smith, LA ;
OBrien, T ;
Katusic, Z .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (23) :12568-12573
[9]   The role of adhesion molecules in atherosclerosis [J].
Chia, MC .
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES, 1998, 35 (06) :573-602
[10]   A major role for VCAM-1, but not ICAM-1, in early atherosclerosis [J].
Cybulsky, MI ;
Iiyama, K ;
Li, HM ;
Zhu, SN ;
Chen, M ;
Iiyama, M ;
Davis, V ;
Gutierrez-Ramos, JC ;
Connelly, PW ;
Milstone, DS .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (10) :1255-1262