AIDS-related vasculopathy: evidence for oxidative and inflammatory pathways in murine and human AIDS

被引:30
作者
Baliga, RS
Chaves, AA
Jing, L
Ayers, LW
Bauer, JA
机构
[1] Ohio State Univ, Colombus Childrens Res Inst, Ctr Cardiovasc Med, Columbus, OH 43205 USA
[2] Ohio State Univ, Coll Pharm, Div Pharmacol, Columbus, OH 43210 USA
[3] Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA
[4] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2005年 / 289卷 / 04期
关键词
endothelial function; inflammation; oxidants;
D O I
10.1152/ajpheart.00304.2005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Increased life expectancy of human immunodeficiency virus (HIV)positive patients has led to evidence of complications apparently not directly related to immunodeficiency or opportunistic infection, including increased cardiovascular risk. We tested the hypothesis that vascular dysfunction occurs in the murine acquired immune deficiency syndrome ( AIDS) model and evaluated potential mechanisms in murine AIDS tissues and relevant human HIV/AIDS vascular tissues. We also investigated endothelial activation and/or endothelial protein nitration and their association with time-dependent vascular dysfunction. At 1 and 5 wk of murine AIDS, statistically significant decreases in KCl contractility and time-dependent contractile deficits in response to phenylephrine were observed. The maximal response (E-max) was reduced by similar to 40% at 10 wk, and EC50 values were significantly changed: 102 +/- 7.3 ng for control vs. 190 +/- 37 and 130 +/- 22 ng at 5 and 10 wk, respectively (P<0.05). Endothelium-dependent relaxation to ACh was decreased (EC50=120 +/- 27 and 343 +/- 94 nM for control and at 10 wk, respectively), whereas the response to an exogenous nitric oxide donor, sodium nitroprusside, remained unchanged, suggesting a specific endothelial dysfunction. Histochemical investigations of the same vascular tissues as well as corresponding coronary endothelium showed an increase in protein 3-nitrotyrosine, intercellular adhesion molecule, and nitric oxide synthase isoforms 2 and 3. These findings were corroborated in concurrent experiments in a cohort of well-cataloged human cardiac microvascular tissues. We have demonstrated, for the first time, a specific functional vasculopathy with endothelial involvement in a murine model of AIDS that was also associated with and correlated to increased oxidative stress and specific endothelial activation. This finding was echoed in a relevant population of human HIV/AIDS patients. Research into sources and intracellular targets of oxidants in this disease could provide important mechanistic insights and may reveal new therapeutic opportunities for this increasingly important cardiovascular disease state.
引用
收藏
页码:H1373 / H1380
页数:8
相关论文
共 52 条
[1]   Frequency of and outcome of acute coronary syndromes in patients with human immunodeficiency virus infection [J].
Ambrose, JA ;
Gould, RB ;
Kurian, DC ;
DeVoe, MC ;
Pearlstein, NB ;
Coppola, JT ;
Siegal, FP .
AMERICAN JOURNAL OF CARDIOLOGY, 2003, 92 (03) :301-303
[2]   Cardiomyopathy and encephalopathy in AIDS [J].
Antinori, A ;
Giancola, ML ;
Alba, L ;
Soldani, F ;
Grisetti, S .
HIV-ASSOCIATED CARDIOVASCULAR DISEASE: CLINICAL AND BIOLOGICAL INSIGHTS, 2001, 946 :121-129
[3]   Premature ageing of the immune system: the cause of AIDS? [J].
Appay, V ;
Rowland-Jones, SL .
TRENDS IN IMMUNOLOGY, 2002, 23 (12) :580-585
[4]   Vascular endothelial toxicity induced by HIV protease inhibitor: Evidence of oxidant-related dysfunction and apoptosis [J].
Baliga R.S. ;
Liu C. ;
Hoyt D.G. ;
Chaves A.A. ;
Bauer J.A. .
Cardiovascular Toxicology, 2004, 4 (2) :199-206
[5]   Oxidative damage and tyrosine nitration from peroxynitrite [J].
Beckman, JS .
CHEMICAL RESEARCH IN TOXICOLOGY, 1996, 9 (05) :836-844
[6]   Arterial stiffness and endothelial dysfunction in HIV-infected children [J].
Bonnet, D ;
Aggoun, Y ;
Szezepanski, I ;
Bellal, N ;
Blanche, S .
AIDS, 2004, 18 (07) :1037-1041
[7]   Interactions between endothelial cells and HIV-1 [J].
Bussolino, F ;
Mitola, S ;
Serini, G ;
Barillari, G ;
Ensoli, B .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2001, 33 (04) :371-390
[8]  
Centers for Disease Control and Prevention (CDC), 2002, MMWR Morb Mortal Wkly Rep, V51, P595
[9]   Cardiomyopathy in a murine model of AIDS: evidence of reactive nitrogen species and corroboration in human HIV/AIDS cardiac tissues [J].
Chaves, AA ;
Mihm, MJ ;
Schanbacher, BL ;
Basuray, A ;
Liu, C ;
Ayers, LW ;
Bauer, JA .
CARDIOVASCULAR RESEARCH, 2003, 60 (01) :108-118
[10]   The effects of HIV infection on endothelial function [J].
Chi, D ;
Henry, J ;
Kelley, J ;
Thorpe, R ;
Smith, JK ;
Krishnaswamy, G .
ENDOTHELIUM-JOURNAL OF ENDOTHELIAL CELL RESEARCH, 2000, 7 (04) :223-242