The natural history of collagen and alpha-actin expression after coronary angioplasty.

BACKGROUND

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is a result of remodeling and deposition of new mass. The new mass is formed by invading and replicating cells and by extracellular matrix (ECM), of which collagens constitute the dominating component. Smooth muscle actin is an important element in cell contraction. We tested the hypothesis that the accumulation of collagen and actin correlates with the development of postinjury luminal narrowing.

METHODS AND RESULTS

Thirty-five pigs underwent balloon angioplasty and were killed 0, 1, 4, 7, 14, 28, and 56 days later. Tissue samples from the left circumflex artery were in paraffin, sectioned, and immunostained for Collagen Types I and III and alpha1-smooth muscle actin. Collagen accumulation was measured separately in intima, media, and adventitia using computerized semiautomatic planimetry. The injury produced a strong healing response, with a marked accumulation of collagen in all three vessel wall layers. However, the accumulation in adventitia began surprisingly early (1 to 4 days after PTCA) and stopped at Day 7, i.e., before luminal narrowing occurred (14 to 28 days after PTCA in our model). Furthermore, a conspicuous accretion of collagen occurred in the injured area of the medial layer. This response attenuated 14 days after PTCA. Neointimal collagen accumulation took place parallel to neointima formation 2 to 4 weeks after injury. Extramedial smooth muscle actin occurred predominantly from Days 4 to 14 in neointima. Only small quantities of actin were observed in the (neo-)adventitia. Furthermore, adventitial actin was a temporary phenomenon that disappeared between Days 14 and 28.

CONCLUSION

Adventitial and medial collagen deposition apparently occurs before luminal narrowing, indicating that the bulk of new mass in adventitia and media is not the cause of vessel remodeling, but possibly stabilizes the vessel wall and impairs compensatory outward remodeling. The accumulation of actin-positive cells and collagen takes place in neointima parallel to luminal narrowing, which suggests that a contraction within the neointimal mass may contribute to the remodeling process.