Extracellular matrix remodeling after balloon angioplasty injury in a rabbit model of restenosis.

Abstract

Remodeling of the vessel wall after balloon angioplasty injury is incompletely understood, and in particular, the role of extracellular matrix synthesis in restenosis has received little attention. The objective of the present study was to determine the sequence of changes in collagen, elastin, and proteoglycan synthesis and content after balloon injury and to relate these changes to growth of the intimal lesions and extent of cell proliferation. In a double-injury non-cholesterol-fed model, right iliac arterial lesions in 43 rabbits were treated with balloon angioplasty, and the rabbits were killed at five time points ranging from immediate to 12 weeks. Vessel wall collagen and elastin content and synthesis were measured after incubation with '4C-proline and separation with a cyanogen bromide extraction procedure. assess cell proliferation. The intimal area significantly increased from 0.27±0.08 to 0.73±0.11 mm2 between 0 and 12 weeks. Intimal and medial cell proliferation were modest and peaked at 1 week (labeling indexes of 4.8% and 3.0%, respectively) and then markedly declined by 2 weeks. Significant increases in collagen, elastin, and proteoglycan synthesis, up to 4 to 10 times above control nondamaged contralateral iliac arteries, were noted at 1, 2, and 4 weeks. These increases in synthesis were accompanied by significant increases in collagen and elastin content (by "=35%) that coincided with the temporal increase in cross-sectional area. Our data suggest that extracellular matrix formation is a major factor in the development of the restenosis lesion. (Circ Res. 1994;75: 650-658.)

Crucial Role of Stromal Cell–Derived Factor-1α in Neointima Formation After Vascular Injury in Apolipoprotein E–Deficient Mice

“…SDF-1␣ binding to proteoglycans has been described recently to enhance SDF-1␣-induced migration of hematopoietic progenitor cells. 22 Because proteoglycan synthesis is increased after balloon angioplasty and therefore proteoglycans contribute significantly to extracellular matrix in neointimal lesions, 23 SDF-1␣ may be released into the circulation early after endothelial denudation but could be bound to proteoglycans in the developing neointimal matrix, thereby shifting its contribution from early mobilization toward a more continuous neointimal recruitment of PBPCs. Beyond its effects on recruitment within the first weeks, local SDF-1␣ may further affect the neointimal SMC architecture, thus contributing to arterial remodeling of injured vessels.…”

Tranilast Suppresses Intimal Hyperplasia in the Balloon Injury Model and Cuff Treatment Model in Rabbits

“…Because of these findings, we investigated the effects of tranilast on the PDGF-induced VSMC migra tion and proliferation. Also, we observed the VSMC syn thesis of collagen, a protein component of the extracel lular matrix, because it is reported that the accumulation of collagen produced by VSMCs is one of the causes of the intimal hyperplasia (2,28). In this study, tranilast inhibited both PDGF-induced VSMC migration and proliferation.…”

“…These cytokines induce VSMC migration from the media to the intima and VSMC proliferation there. The VSMCs that have migrated and proliferated not only release cytokines, which make other VSMCs migrate and proliferate, but also produce an extracellular matrix (2)(3)(4). The precise mechanism of intimal hyperplasia in the perivascular manipulation model is yet unknown; However, it is reported that leukocytes accumulate in the intima of the perivascularly manipulated area, where their products cause endothelial denudation (20, 27).…”

“…Although PTCA is successful, 30-50% of patients suffer from vascular reste nosis within 6 months after the operation (1). The reste nosis results from vascular smooth muscle cell (VSMC) migration from the media to the intima, where cells pro liferate and cause on excessive accumulation of extracel lular matrix produced by themselves (2)(3)(4). The precise mechanism of the restenosis is unknown; however, it is reported that some cytokines, such as platelet-derived growth factor (PDGF), are implicated in the development of the restenosis (4 6).…”

Losartan reduces collagen content and intimal thickening of iliac arteries after balloon injury in rabbits

“…10 The arterial remodelling 9 in restenosis pathophysiology has further fuelled the interest in understanding matrix changes after balloon arterial injury. Collagen, the most abundant ECM protein accumulated after balloon injury, 3 may be an important factor in development of stenosis and restenosis. Recently, considerable effort has been devoted to exploring the role of the renin-angiotensin-aldosterone system (RAAS) in vascular proliferative responses to injury.…”