Role of growth factors in angiogenesis and enlargement of coronary collateral channels.

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Although mechanical and humoral factors documented in the presence of myocardial ischemia augment collateral vessel development, the causality and the physiological significance of these factors in sngiogenesis and/or anastomotic channel development remain unclarified. Experimental studies have commonly used a canine model because of its easy induction of anastomotic channel enlargement during progression of gradual coronary stenosis, which failed to identify the origin of coronary collteral channels. Since rabbits lack preexisting collaterals, effects of abrupt coronary occlusion and coronary stenosis due to arteriosclerosis on collateral developments were examined in rabbits.1) Post-mortem angiograms 1,4, and 12 weeks after coronary ligation did detect collateral channels in only 10% of cases. This number was smaller than than those observed in acanine or porcine model. To elucidate how hyperlipidemia modulates the progrekssion of coronary stenosis and its resultant collateral development, post-mortem angiograms were examined in WHHL (Watanabe Heritable Hyperlipidemic) rabbits of 7 months old. Although severe narrowing (>90%diameter stenosis) was detected in all rabbits at the proximal portion of the left or right coronary arteries, collateral channels were not observed.2) To modulate angiogenesis in the ventricular myocardium in situ, plasmids assembled with ANP gene were directly introduced into the left ventricular wall and Northern blot analysis and immuno-histochemical studies were operformed 7 days after the gene transfer. Expression of ANP gene in the myocytes was not so strong to detect physiological effcts of ANP.We are looking for a more efficient vector for this purpose.