Improvement of contractility accompanies angiogenesis rather than arteriogenesis in chronic myocardial ischemia

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• 作者：Claudia Heilmann ; Caterina Kostic ; Bodo Giannone ; Andrea Busse Grawitz ; Werner Armbruster ; Georg Lutter ; Friedhelm Beyersdorf and Heike Gö ; bel
• 刊名：Vascular Pharmacology
• 出版年：2006
• 出版时间：May 2006
• 年：2006
• 卷：44
• 期：5
• 页码：326-332
• 全文大小：180 K

文摘

Introduction

Growth factor therapy provides a therapeutic alternative for “no option” patients with coronary disease. Fibroblast Growth Factor-2 (FGF-2) predominantly stimulates angiogenesis, the growth of new capillaries, whereas Monocyte Chemoattractant Protein-1 (MCP-1) is considered an arteriogenic agent. We hypothesised a synergetic effect of FGF-2 and MCP-1 in ischemic myocardium.

Methods

A severe coronary stenosis was created in pigs. After one week, chronic ischemia was confirmed by angiography, echocardiography, reduced ejection fraction, and increase of marker enzymes. FGF-2, MCP-1, both, or vector only were then injected intramyocardially as plasmid DNA in the impaired area. Regional contractility and number of capillaries and arterial vessels were evaluated after three months.

Results

FGF-2, FGF-2 + MCP-1, and vector, but not MCP-1 alone improved regional contractility at rest, whereas only FGF-2 alone ameliorated function under stress conditions. Angiogenesis in the ischemic area was stimulated by FGF-2 compared to MCP-1. In contrast, MCP-1 induced arteriogenesis relative to FGF-2.

Conclusion

Differences for vessel growth and regional function were apparent between FGF-2 and MCP-1. This contrast could allow the speculation that development of a flow reserve in chronically ischemic myocardium is linked to angiogenesis rather than to arteriogenesis. No additional benefits were seen following combined therapy.