American College of Cardiology
48th Annual Scientific Session
March 7-10, 1999

Does Angiogenesis Promote Perfusion or Encourage 
Plaque Growth (help or hurt)?

	Angiogenesis is the process whereby new blood 
vessels are grown to service specific areas in the body,
like the heart. Many proteins either inhibit or 
stimulate angiogenesis. Dr. Judah Folkman delivered
the lecture: "Angiogenic Therapy for the Heart."

Stimulators of Angiogenesis

	Angiogenic stimulation in patients with 
coronary artery disease (CAD) may have risks. Some data 
suggest that artherosclerotic plaque growth may depend
on angiogenesis. New, growing micro-blood-vessels have
been seen growing in plaques. In other words, causing 
angiogenesis, we may also be building up the very same 
plaque that caused clogged arteries in the first place.
	The search for stimulators of angiogenesis
began recently. Dr. Jeffrey Isner presented data in 1997
showing that injection of VEGF - vascular endothelial
growth factor - into the legs of patients with severe 
peripheral vascular disease, increased blood vessel 
growth, decreased limping, and increased wound healing.
	Another study showed that FGF - fibroblast growth
factor - injected intramuscularly in the heart led to an 
increase in growth of new blood vessels supporting 
coronary arteries (collaterization).
	Many questions remain unanswered: Which protein 
stimulator is best (VEGF or FGF or other)? What is the 
best dose? How should the growth factor be delivered 
(plasmid, virus, intracoronary or intramyocardial 
injection)?

Inhibitors of Angiogenesis

	Dr. Folkman also reported on drugs that inhibit
vascular growth in atherosclerotic plaques. Angiostatin
and endostatin were both discovered this past year. They 
cause a 99% reduction in vascular growth.

Conclusion

	It is unclear how angiogenic inhibitors such as
endostatin and stimulators such as the VEGF and FGF gene
products will be used in treating ischemic heart disease.
Encouraging the growth of coronary arteries would be 
helpful in patients with chronic ischemia who cannot 
have revascularization like bypass surgery. However, 
encouraging new vascularization may lead to more 
extensive atherosclerotic plaque formation. Catch 22?
	As exciting as the theory and early clinical tests
on angiogenesis are, the potential for harm exists. For 
example, tumor growth might result from efforts to cause
myocardial angiogenesis. The unanswered questions
on choices of drugs, dose and delivery, limit our ability
to widely use these drugs anytime soon.