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

尽管在心肌缺血时已有文献记载的机械和体液因素可促进侧支血管的发育，但这些因素在血管形成和/或吻合口通道发育中的因果关系和生理意义仍不清楚。实验研究通常采用犬模型，因为在冠状动脉逐渐狭窄的过程中，容易导致吻合口通道扩大，无法确定冠脉侧支通道的来源。1)冠状动脉结扎后1、4、12周的尸检血管造影术仅有10%的兔发现侧支循环。这个数字比在乌头碱或猪模型中观察到的要小。为阐明高脂血症如何调节冠状动脉狭窄的进展及其侧支循环的发展，对7月龄渡边遗传性高脂血症(WHHL)兔进行了尸检。在左、右冠状动脉近端均可见重度狭窄(&gt；90%管径狭窄)，但未观察到侧支循环；2)为调节心肌血管生成，将携带ANP基因的重组质粒直接导入左室壁，7天后进行Northern印迹分析和免疫组织化学研究。ANP基因在心肌细胞中的表达不是很强，无法检测ANP的生理作用，我们正在寻找一种更有效的载体来检测ANP的生理作用。

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.