Expression of VEGF and angiopoietins-1 and -2 during ischemia-induced coronary angiogenesis

被引:79
作者
Matsunaga, T
Warltier, DC
Tessmer, J
Weihrauch, D
Simons, M
Chilian, WM
机构
[1] Louisiana State Univ, Dept Physiol, Hlth Sci Ctr, New Orleans, LA 70112 USA
[2] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
[3] Med Coll Wisconsin, Dept Anesthesiol, Ctr Cardiovasc, Milwaukee, WI 53226 USA
[4] Dartmouth Coll Sch Med, Div Cardiol, Dept Med, Hanover, NH 03755 USA
[5] Louisiana State Univ, Ctr Cardiovasc Dis, Hlth Sci Ctr, New Orleans, LA 70112 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2003年 / 285卷 / 01期
关键词
coronary collateral; vascular endothelial growth factor; Tie-2;
D O I
10.1152/ajpheart.00621.2002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The mechanisms underlying coronary capillary growth in response to ischemia are undefined. We hypothesized that the expression of vascular endothelial growth factor (VEGF) and angiopoietin (Ang)/Tie-2 were involved in capillary growth as an adaptation to ischemia. To test this hypothesis we measured capillary density, and the expressions of VEGF, Ang-1, Ang-2, and the Tie-2 receptor and its phosphorylation state during repetitive episodes of myocardial ischemia in chronically instrumented canines. Repetitive episodes of ischemia were induced by multiple (once/ hour; 8/day), brief (2 min) occlusions of the left anterior descending coronary artery for 1, 7, 14, or 21 days. A sham group received the same instrumentation as the experimental groups but not the occlusion protocol. Collateral blood flow ( microspheres) progressively increased from 9 +/- 3 to 83 +/- 10 ml.min(-1).100 g(-1) on day 21. Capillary density increased at day 7 from 2,378 +/- 53 ( sham) to 2,962 +/- 60/mm(2), but it decreased to 2,594 +/- 39/mm(2) at day 21. Both VEGF and Ang-2 expression in myocardial interstitial fluid ( Western analyses) peaked at day 3 of the repetitive occlusions but waned thereafter. In contrast the expression of Ang-1 remained relatively constant at all times in the occlusion groups. In shams, the expression of VEGF and Ang-2 was low and constant at all times. Tie-2 phosphorylation myocardial decreased decreased at day 7 but increased at 21 days of occlusions (P < 0.05). Our results indicate that capillary density was augmented by myocardial ischemia, but after development of collaterals and restoration of flow to the ischemic zone, capillary density returned to control levels. The change in capillary density paralleled with VEGF and Ang-2 expression but was inversely related to Tie-2 phosphorylation. We speculate the coronary angiogenesis is a coordinated event involving the expression of both VEGF and Ang-2 and that therapeutic angiogenic strategies may ultimately require treatment with more than a single factor.
引用
收藏
页码:H352 / H358
页数:7
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