The cellular mechanism of growth of coronary collateral vessels (adaptive arteriogenesis) 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, the collateral vessels increased in wall thickness by the formation of a
neointima without
luminal narrowing. We report here for the first time that extensive
vascular remodeling including migration, proliferation and apoptosis in all cell types takes place during the growth phase but not in more mature vessels. The most obvious difference with normal vessels is the reiteration of an embryonal expression pattern in smooth muscle cells of the
neointima which includes a significant reduction of
desmin and alpha-smooth muscle actin,
calponin and
vinculin.
Fibronectin as a promoter of migration and adhesion was abundant, its antagonist
tenascin and
chondroitin sulfate showed patchy localization. A completely new finding in arteriogenesis is the involvement of mast cells releasing
histamine and
serotonin and probably
cytokines. Vascular
protein expression returned to almost normal at 8 weeks indicating cessation of remodeling. We conclude that in collateral vessel development an altered cellular and matrix
protein expression is involved in a drastic case of positive
vascular remodeling finally resulting in mature vessels 20-fold increased in size which are capable of maintaining the functional and structural integrity of the myocardium at risk.