VEGF-mediated angiogenesis is impaired by angiotensin type 1 receptor blockade in cardiomyopathic hamster hearts

被引:41
作者
Shimizu, T [1 ]
Okamoto, H [1 ]
Chiba, S [1 ]
Matsui, Y [1 ]
Sugawara, T [1 ]
Akino, M [1 ]
Nan, J [1 ]
Kumamoto, H [1 ]
Onozuka, H [1 ]
Mikami, T [1 ]
Kitabatake, A [1 ]
机构
[1] Hokkaido Univ, Grad Sch Med, Dept Cardiovasc Med, Kita Ku, Sapporo, Hokkaido 0608638, Japan
关键词
ACE inhibitors; growth factors; heart failure; microcirculation; renin angiotensin system;
D O I
10.1016/S0008-6363(02)00843-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Coronary microcirculation plays an important role in the progression of cardiac remodeling. Among angiogenic factors, it has been reported that angiotensin II may contribute to neovascularization. However, it is unknown whether inhibition of the renin-angiotensin system suppresses angiogenesis, especially within the heart. Our aim was to evaluate the effects of the angiotensinconverting enzyme inhibitor enalapril and the angiotensin II receptor type I blocker valsartan on cardiac microvasculature, function, vascular endothelial growth factor (VEGF) expression, and survival in cardiomyopathic hamsters. Methods: Male cardiomyopathic hamsters (BIO TO2) were administered either a placebo (group C), enalapril (30 mg/kg/day) (group E), or valsartan (40 mg/kg/day) (group V), starting at the age of 6 weeks. This continued until death. Hemodynamic study, histological analysis, and northern blot analysis were performed at 39 weeks. Results: Group V showed significant increases in percent fibrosis, end diastolic pressure, and LV dP/dt min, and significant decreases in percent fractional shortening, LV dP/dt max, capillary density, and the level of mRNA expression of VEGF compared with group C. Group E showed significant increases in percent fractional shortening while the capillary density and level of mRNA expression of VEGF were unchanged. The 300-day survival rate was significantly lower in group V (25.0%) but higher in group E (100%) than that of group C (66.7%). Conclusions: Therapy with valsartan may have adverse effects on survival rate concomitant with the progression of cardiac remodeling owing to impaired VEGF-mediated angiogenesis. Therapy with enalapril has a neutral effect on VEGF-mediated angiogenesis; leading to the suppression of cardiac remodeling and an increase in life expectancy. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:203 / 212
页数:10
相关论文
共 32 条
[1]   Chronic AT1 receptor blockade and angiotensin-converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathic hamsters:: effects on cardiac hypertrophy and survival [J].
Bastien, NR ;
Juneau, AV ;
Ouellette, J ;
Lambert, C .
CARDIOVASCULAR RESEARCH, 1999, 43 (01) :77-85
[2]   New look at myocardial infarction: toward a better aspirin [J].
Bing, RJ ;
Yamamoto, T ;
Yamamoto, M ;
Kakar, R ;
Cohen, A .
CARDIOVASCULAR RESEARCH, 1999, 43 (01) :25-31
[3]   Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188 [J].
Carmeliet, P ;
Ng, YS ;
Nuyens, D ;
Theilmeier, G ;
Brusselmans, K ;
Cornelissen, I ;
Ehler, E ;
Kakkar, VV ;
Stalmans, I ;
Mattot, V ;
Perriard, JC ;
Dewerchin, M ;
Flameng, W ;
Nagy, A ;
Lupu, F ;
Moons, L ;
Collen, D ;
D'Amore, PA ;
Shima, DT .
NATURE MEDICINE, 1999, 5 (05) :495-502
[4]   BETA-ADRENOCEPTOR BLOCKING-DRUGS AND ISOPRENALINE - CENTRAL EFFECTS ON CARDIOVASCULAR PARAMETERS [J].
COHEN, Y ;
LINDENBAUM, A ;
MIDOLMONNET, M ;
PORQUET, D ;
WEPIERRE, J .
BRITISH JOURNAL OF PHARMACOLOGY, 1979, 65 (03) :389-394
[5]   A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure [J].
Cohn, JN ;
Tognoni, G .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (23) :1667-1675
[6]  
DOMINIQUE T, 2002, J BIOL CHEM, V277, P2028
[7]   Angiotensin AT1 receptor signalling modulates reparative angiogenesis induced by limb ischaemia [J].
Emanueli, C ;
Salis, MB ;
Stacca, T ;
Pinna, A ;
Gaspa, L ;
Maddeddu, P .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 135 (01) :87-92
[8]   Targeting kinin B1 receptor for therapeutic neovascularization [J].
Emanueli, C ;
Salis, MB ;
Stacca, T ;
Pintus, G ;
Kirchmair, R ;
Isner, JM ;
Pinna, A ;
Gaspa, L ;
Regoli, D ;
Cayla, C ;
Pesquero, JB ;
Bader, M ;
Madeddu, P .
CIRCULATION, 2002, 105 (03) :360-366
[9]   Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart [J].
Giordano, FJ ;
Ping, PP ;
McKirnan, MD ;
Nozaki, S ;
DeMaria, AN ;
Dillmann, WH ;
MathieuCostello, O ;
Hammond, HK .
NATURE MEDICINE, 1996, 2 (05) :534-539
[10]  
HAYES CE, 1974, J BIOL CHEM, V249, P1904