ADVENTITIAL REMODELING AFTER CORONARY ARTERIAL INJURY

Background Intraluminal thrombus formation and medial smooth muscle (S M) tell proliferation are recognized responses of the arterial system to injury. Ln contrast to these well-characterized processes during va scular repair, changes involving the adventitia have been largely negl ected in previous studies. Hence, the goal of this investigation was t o assess the response of the adventitia to coronary arterial injury. M ethods and Results Adventitial changes in porcine coronary arteries su bjected to medial injury were characterized by immunohistochemistry, h istochemistry, and microscopic morphometry. The rapid development of a hypercellular response in the adventitia was evident 3 days after bal loon-induced medial injury. Cell proliferation, as assessed by prolife rating cell nuclear antigen immunostaining, reached the maximum level in the adventitia at 3 days, whereas at 14 and 28 days, the number of replicating cells reverted toward the baseline. The proliferating acti vity in the adventitia exceeded that seen in the media at all times af ter injury. To further define the changes in the phenotype of adventit ial cells, the expression of three cytoskeletal proteins (vimentin, al pha-SM actin, and desmin) was characterized. Fibroblasts in normal adv entitia expressed vimentin but no alpha-SM actin or desmin. After inju ry, these cells acquired characteristics of myofibroblasts expressing alpha-SM actin, which peaked at 7 and 14 days. Desmin expression was p atchy in the adventitia, as opposed to its homogeneous distribution in medial SM cells. The modulation of fibroblast phenotype was transient , inasmuch as alpha-SM actin immunostaining declined at 28 days after injury, when dense, collagen-rich scar was evident within the adventit ia. The above-described changes involving hypercellularity of the adve ntitia, myofibroblast formation, and fibrosis were associated with a s ignificant focal adventitial thickening at 3, 7, 14, and 28 days after injury (P<.01 versus uninjured coronary arteries). Conclusions This s tudy demonstrates the involvement of the adventitia in the vascular re pair process after medial injury. The hypercellularity of the adventit ial layer, proliferation of fibroblasts, and modulation of their pheno type to myofibroblasts are associated with the development of the thic kened adventitia. It is postulated that these phenomena affect vascula r remodeling and may provide an important insight into the mechanisms of vascular disorders.