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

虽然机械和体液因素记录在心肌缺血的存在下增加侧支血管的发展，因果关系和生理意义的这些因素在sngiogenesis和/或吻合通道的发展仍然不清楚。实验研究通常使用犬模型，因为其在冠状动脉逐渐狭窄的进展过程中容易诱导吻合口通道扩大，无法识别冠状动脉颈静脉通道的起源。由于家兔缺乏预先存在的侧支循环，因此在家兔中检查了由于动脉硬化导致的突然冠状动脉闭塞和冠状动脉狭窄对侧支循环发展的影响。1）冠状动脉结扎后1、4和12周的死后血管造影仅在10%的病例中发现了侧支循环。该数量小于在乌头碱或猪模型中观察到的数量。为了阐明高脂血症如何调节冠状动脉狭窄的进展及其导致的侧支循环的发展，对7月龄的WHHL（Watanabe遗传性高脂血症）家兔进行了死后血管造影检查。2）将重组质粒直接导入兔左心室壁，在基因转染7天后进行北方印迹分析和免疫组化研究，观察ANP基因在心肌血管形成中的作用。ANP基因在心肌细胞中的表达不强，不能检测ANP的生理效应，我们正在寻找一种更有效的表达载体。

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.