Up-regulation of vascular endothelial growth factor mRNA and angiogenesis after transmyocardial laser revascularization.
BACKGROUND
Angiogenesis has been proposed as a potential mechanism whereby transmyocardial laser revascularization (TMLR) has provided clinical relief of angina. Experimental work has found histologic evidence supporting this, as well as an improved response when angiogenic growth factors have been added to TMLR. The purpose of this study was to demonstrate that the molecular response to TMLR was an increase in the production of endogenous vascular endothelial growth factor to promote angiogenesis.


METHODS
Ameroid constrictors were placed on the proximal circumflex artery in 12 domestic pigs. After a chronic ischemic zone was established the animals were randomly divided into two groups. In the TMLR group the ischemic zone was treated with carbon dioxide laser. In the control group the ischemic zone was untreated. Six weeks later the animals were sacrificed, and sections from the ischemic zone and the nonischemic zone were submitted for immunohistochemical, histologic, and molecular analysis. Messenger RNA was obtained from northern blot analysis after being probed with vascular endothelial growth factor.


RESULTS
There was a twofold increase in the vascular endothelial growth factor messenger RNA in the ischemic zone of the TMLR group compared with the control group. Additionally, there was a threefold increase in the number of new blood vessels in the ischemic zone of the TMLR group compared with the control group.


CONCLUSIONS
Transmyocardial laser revascularization promotes angiogenesis by upregulation of vascular endothelial growth factor. The resulting angiogenesis could be the principle mechanism for the clinical efficacy of TMLR.
Horvath
K A
KA
Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, Illinois 60611, USA. khorvath@nmh.org
Chiu
E
E
Maun
D C
DC
Lomasney
J W
JW
Greene
R
R
Pearce
W H
WH
Fullerton
D A
DA
D000818:Animals; D015152:Blotting, Northern; D003326:Coronary Circulation; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005169:Factor VIII / Q000032:analysis; D007150:Immunohistochemistry; D053685:Laser Therapy; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000601:surgery; D009204:Myocardial Revascularization; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005169:Factor VIII