Neointima formation after vascular stent implantation. Spatial and chronological distribution of smooth muscle cell proliferation and phenotypic modulation.

Abstract

Intravascular stents have proved useful as angioplasty devices, but intimal hyperplasia after stent implantation remains an unsolved problem. In the present study, we analyzed the spatial and chronological distribution of proliferation and phenotypes of smooth muscle cells (SMCs) in rabbit aortas during the process of neointima formation after stent implantation (Gianturco's Z type) by immunohistochemistry for proliferating cell nuclear antigen (PCNA) and myosin heavy chain isoforms (SMI, SM2, and SMemb). Stent implantation induced regional injury in the arterial wall. Medial SMCs then began to proliferate adjacent to the injured SMCs, maximally on day 4 (PCNA index in the media: 3.9±3.4%[mean±SD]), and were modulated to the embryonic phenotype (SMemb-positive and SM2-negative). They migrated into I ntravascular stents have been extensively investigated as tools of angioplasty and proved useful in elastic recoil, restenosis, and dissection after balloon angioplasty.1 They have also been applied to various sites of stenotic lesions, including coronary arteries.1 -4 Several clinical trials have demonstrated that intracoronary stenting may be more effective than percutaneous transluminal coronary angioplasty (PTCA) in maintaining long-term vessel patency and may reduce the incidence of restenosis after angioplasty. "9 Such reduction in the restenosis rate is considered to be due to a larger acute gain obtained by stent implantation, although late loss of diameter is greater after stenting than that after PTCA. 7 9 Thus, restenosis after stenting still remains an unsolved problem.Pathological specimens of restenotic lesions after stenting show intimal hyperplasia, composed of abundant smooth muscle cells (SMCs) mixed with various degrees of connective tissue matrix. This study was presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.Reprint requests to Hikaru Matsuda, MD, First Department of Surgery, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan.© 1994 American Heart Association, Inc.the intima and proliferated most frequently on day 7 (PCNA index in the intima: 20.3±5.5%) and subsequently led to fibrocellular neointima formation at 2 weeks and later. At 1 month after implantation and later, SMC proliferation was rare, and the phenotype of intimal SMCs was gradually returning to the adult type (SMemb-negative and SM2-positive). Thus, this stent implantation model demonstrates that the regional effect on arterial wall by stenting leads to neointima formation through transient and regional proliferation and migration of SMCs and their phenotypic modulations.

Management and Clinical Outcome of Acute Basilar Artery Dissection

“…Therefore, the treatment goals for ruptured dissection are prevention from rebleeding in the acute stage and promotion of healing as rapidly as possible. A stent promotes neointima formation along the stent struts in experimental models 13,14 and may also prevent rebleeding in the acute stage by flow redirection and lowering of the wall stress of a dissecting pseudoaneurysm. 15 As seen in this study, however, a single stent may not be sufficient to prevent rebleeding.…”

Vascular Apolipoprotein E Expression and Recruitment from Circulation to Modulate Smooth Muscle Cell Response to Endothelial Denudation

“…The activated VSMC remain metabolically active until the phenotype change is reversed. 5 One protein that has been shown to modulate vascular response to injury is apolipoprotein (apo) E. This protein is well-known for its role in lipid metabolism, particularly as associated with very low density lipoprotein (VLDL) and some high density lipoprotein (HDL) particles. 6 ApoE has also been shown to have several anti-atherogenic effects, both through its role in lipid metabolism, as well as through anti-oxidant properties.…”

Burgeoning Dilemmas in the Management of Diabetes and Cardiovascular Disease

“…Blood vessels in nondiabetic experimental animals subjected to stenting exhibit neointimal formation attributable to migration and proliferation of vascular smooth muscle cells, as well as to a change in their phenotype from contractile to proliferative. 8 A paradoxical decrease in atherosclerotic plaque mass has been seen in patients with diabetes treated with insulin and is considered to reflect "impaired adaptive remodeling or shrinkage of arterial wall, of plaque, or both." 9 "Intimal hypercellular tissue content is reduced in restenotic tissue" in diabetic patients exhibiting restenosis after PCI consistent with phenomena other than proliferation of vascular smooth muscle cells.…”