ADVENTITIAL MYOFIBROBLASTS CONTRIBUTE TO NEOINTIMAL FORMATION IN INJURED PORCINE CORONARY-ARTERIES

Background The adventitia undergoes remodeling changes after a deep me dial coronary injury. Because this process is associated with the form ation of adventitial myofibroblasts, which resemble medial smooth musc le (SM) cells, we have examined myofibroblast involvement in the devel opment of neointima. Methods and Results In a porcine model, severe en doluminal coronary injury resulted in fibroblast proliferation and adv entitial remodeling. Significant adventitial responses were associated with increased neointimal formation (P<.01). To examine the contribut ion of adventitial cells to the development of neointima, proliferatin g cells were labeled with bromodeoxy-uridine (BrdU) at 12 and 24 hours after injury, and their subsequent localization was determined by imm unohistochemistry (n=24). At 2 to 3 days after severe injury, the adve ntitia contained numerous BrdU-labeled cells (37+/-4%): whereas the me dia demonstrated infrequent labeled cells (4+/-1%). Adventitial cells lacked alpha-SM actin and desmin, which distinguished them from medial SM cells. At 7 to 8 days, some labeled cells acquired characteristics of myofibroblasts expressing ru-SM actin. They were found to transloc ate to the gap between dissected media and contributed to the formatio n of neointima (76+/-19%). At 18 to 35 days, labeled cells were abunda nt in the neointima (86+/-5%). They showed uniform immunostaining for alpha-SM actin but not for desmin, thereby differing from medial SM ce lls and blood-borne cells. Conclusions This study demonstrates translo cation of adventitial fibroblasts to neointima, their phenotypic modul ation to myofibroblasts, and distinct characteristics of myofibroblast s within neointima after severe endoluminal coronary injury. These fin dings suggest the significance of vascular fibroblasts in the process of arterial repair.