Immuohistochemical study on smooth muscle cell proliferation, pheno-typic modulation, and extracellular matrix accumulation in venous arterial grafts in rabbits

摘要

Objective: To study the kinetics and distribution of smooth muscle cell (SMC) proliferation, phenotypic modulation, and various extracellular matrix (ECM) components accumulation during vein graft remodeling. Methods: Normal vein and vein graft in carotid arteries were examined on d 4, d 7, d 14, d 60 and d180 after bypass grafting with immunohistochemical markers of cellular proliferation (proliferating cell nuclear antigen, PCNA), cytoskeletal protein production (α-actin SMC), myosin heavy chain (MHO iso-forms, ECM proteins, and histochemistry (hematoxylin eosin and Elastica-van Gieson stain). Results: Normal veins demonstrated an extremely low level of cellular proliferation and expressed as adult phenotype SM-Cs in media. After bypass grafting, medial SMCs in the graft appeared to be damaged and began to proliferate on d 4, and subsequently migrated and formed the neointima on d 7. Thereafter, the neointima thickened throughout the 180-day period of the experiment, although the neointimal SMC proliferation decreased after d 14. Meanwhile SMCs underwent a distinct phenotypic change from normal adult type to embryonic type. On d 60, embryonic phenotype SMCs began to return to the adult phenotype, but remain to be present in the neointima for as long as 180 d. ECM components including type I collagen, heparin sulfate proteoglucan (HSPG), and dermatan sulfate proteoglcan (decorin) were detected within the neointima on d 7. Thereafter , the accumulation of ECM increased progressively with time. On d 180, a large amount of ECM components were found in the neointima. HSPG mainly accumulated in the superficial and cellular region of the neointima, decorin, on other hand, located in hypocellular area deep in neointima. Type I collagen scatted in both regions. The elastic fibers became rich and arranged continuously in the neointima. Conclusion: The neointima of vein graft was initially formed by proliferation of the embryonic-type SMCs and then thickened infinitely due to ECM accumulation. Prolonged existence of the embryonic-type SMCs in the neointima may contribute to ECM accumulation and increase in the neointima thickness infinitely, which may predispose accelerated stenosis in the vein graft.