Myofibroblast involvement in glycosaminoglycan synthesis and lipid retention during coronary repair

Myofibroblasts of adventitial origin have been linked to neointimal formati on and remodeling after coronary injury. Accordingly, the goal of this stud y was to examine whether myofibroblasts contribute to focal accumulation of glycosaminoglycans (GAGs) and lipids during coronary repair. GAG synthesis was assessed by ex vivo labeling of balloon-injured porcine coronary arter ies with C-14-glucosamine. The synthesis of total GAGs transiently increase d at 8 days in the normolipemic model (a 2.2-fold increase over baseline, p < 0.05). The majority of newly synthesized GAGs were sensitive to chondroi tin ABC lyase (chondroitin/dermatan sulfate GAGs). Versican was localized t o myofibroblast-rich regions in the adventitia and neointima [positive for alpha-smooth muscle (SM) actin, negative for h-caldesmon and SM myosin heav y chain]. In contrast, the adjacent SM-rich media showed no increase in ver sican expression. The association between injury-induced GAG accumulation a nd lipid retention was examined at 2 weeks after coronary injury in the hyp erlipemic model. Lipid (Oil Red O) accumulated in the neointima and adventi tia, but not in the adjacent media. Coronary repair under hyperlipemic cond itions was associated with macrophage infiltration (19 +/- 5 vs. 3 +/- 2% o f neointimal cells in normolipemic animals, p < 0.001) and increased neoint imal formation (1.8 +/- 0.5 vs. 1.0 +/- 0.3 mm(2) in normolipemic animals, p < 0.01), in conclusion, this study demonstrated a transient increase in G AG synthesis following coronary injury. Chondroitin sulfate proteoglycans ( e.g. versican) were rapidly synthesized by activated adventitial and neoint imal cells which could contribute to early lipid retention in injured vesse ls. Copyright (C) 2000 S. Karger AG, Basel.