Clinical applications of cardiovascular angiogenesis.
Angiogenesis is fundamental to both normal physiologic (wound healing) and pathologic (cancer) processes. Manipulation of divergent angiogenic signals promises effective therapy of atherosclerotic cardiovascular disease. Positive proangiogenic strategies promise collateral circulation to ischemic territories, while negative antiangiogenic strategies starve the fibromuscular proliferation within the atherosclerotic lesion. Indeed, recent phase 1 trials suggest that delivering DNA or recombinant protein to the site of vascular occlusion may stimulate physiologically significant collateral circulation in chronically ischemic myocardium. While symptomatic and functional improvement has been documented, toxicity profiles and effects on long-term patient survival are still unclear. The purposes of this article are as follows: (1) to review the pathophysiologic basis for pro- and antiangiogenic strategies in the treatment of cardiovascular disease, (2) to examine the clinical trials of proangiogenic gene or recombinant protein delivery into ischemic beds, and conversely, (3) to explore antiangiogenic strategies in the prevention and treatment of intimal neovascularization and smooth muscle proliferation within the vessel wall.
Zimmerman
M A
MA
The Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA. michael.zimmerman@UCHSC.edu
Selzman
C H
CH
Raeburn
C D
CD
Calkins
C M
CM
Barsness
K
K
Harken
A H
AH
D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000188:drug therapy; D016228:Endothelial Growth Factors / Q000627:therapeutic use; D006801:Humans; D008222:Lymphokines / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000178:diet therapy / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors