Vascular remodeling and altered protein expression during growth of coronary collateral arteries

The cellular mechanism of growth of coronary collateral vessels (adaptive a rteriogenesis) is still poorly understood. To define a possible role of an altered expression pattern of cellular and matrix proteins in this process we implanted a constricting device around the left circumflex artery in 25 canine hearts and sacrificed the animals at the time of initiation (3 weeks ), high activity (6 weeks) and discontinuation (8 weeks) of vessel growth. Methods were electron microscopy, labeling with Ki-67, the TUNEL method and immunofluorescence with confocal laser microscopy. As described earlier, t he collateral vessels increased in wall thickness by the formation of a neo intima without luminal narrowing. We report here for the first time that ex tensive vascular remodeling including migration, proliferation and apoptosi s in all cell types takes place during the growth phase but not in more mat ure vessels. The most obvious difference with normal vessels is the reitera tion of an embryonal expression pattern in smooth muscle cells of the neoin tima which includes a significant reduction of desmin and ct-smooth muscle actin, calponin and vinculin. Fibronectin as a promoter of migration and ad hesion was abundant, its antagonist tenascin and chondroitin sulfate showed patchy localization. A completely new finding in arteriogenesis is the inv olvement of mast cells releasing histamine and serotonin and probably cytok ines. Vascular protein expression returned to almost normal at 8 weeks indi cating cessation of remodeling. We conclude that in collateral vessel devel opment an altered cellular and matrix protein expression is involved in a d rastic case of positive vascular remodeling finally resulting in mature ves sels 20-fold increased in size which are capable of maintaining the functio nal and structural integrity of the myocardium at risk. (C) 1998 Academic P ress.