(Circulation. 1996;93:340-348.)
© 1996 American Heart Association, Inc.
Articles |
Adventitial Remodeling After Coronary Arterial Injury
From the Department of Medicine (Cardiology), Thomas Jefferson University, Philadelphia, Pa.
Correspondence to Andrew Zalewski, MD, Thomas Jefferson University, 1025 Walnut St, Suite 410N, Philadelphia, PA 19107.
Background Intraluminal thrombus formation and medial smooth muscle (SM) cell proliferation are recognized responses of the arterial system to injury. In contrast to these well-characterized processes during vascular repair, changes involving the adventitia have been largely neglected in previous studies. Hence, the goal of this investigation was to assess the response of the adventitia to coronary arterial injury.
Methods and Results Adventitial changes in porcine
coronary arteries subjected to medial injury were characterized
by immunohistochemistry, histochemistry, and microscopic morphometry.
The rapid development of a hypercellular response in the adventitia was
evident 3 days after balloon-induced medial injury. Cell
proliferation, as assessed by proliferating 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
activity in the adventitia exceeded that seen in the media at all times
after injury. To further define the changes in the phenotype of
adventitial cells, the expression of three cytoskeletal proteins
(vimentin, 
-SM actin, and desmin) was characterized. Fibroblasts in
normal adventitia expressed vimentin but no -SM actin or desmin.
After injury, these cells acquired characteristics of myofibroblasts
expressing -SM actin, which peaked at 7 and 14 days. Desmin
expression was patchy in the adventitia, as opposed to its
homogeneous distribution in medial SM cells. The modulation
of fibroblast phenotype was transient, inasmuch as -SM actin
immunostaining declined at 28 days after injury, when
dense, collagen-rich scar was evident within the adventitia. The
above-described changes involving hypercellularity of the
adventitia, myofibroblast formation, and fibrosis were associated with
a significant focal adventitial thickening at 3, 7, 14, and 28 days
after injury (P<.01 versus uninjured coronary
arteries).
Conclusions This study demonstrates the involvement of the adventitia in the vascular repair process after medial injury. The hypercellularity of the adventitial layer, proliferation of fibroblasts, and modulation of their phenotype to myofibroblasts are associated with the development of the thickened adventitia. It is postulated that these phenomena affect vascular remodeling and may provide an important insight into the mechanisms of vascular disorders.
Key Words: adventitia • remodeling • myofibroblasts • angioplasty • restenosis
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