Inflammation and Restenosis in the Stent Era

Abstract

Abstract-The pathophysiology of restenosis involves early elements of direct injury to smooth muscle cells, deendothelialization, and thrombus deposition. Over time, this leads to smooth muscle cell proliferation/migration and extracellular matrix deposition. There is an increasing body of evidence to suggest that inflammation plays a pivotal role linking early vascular injury to the eventual consequence of neointimal growth and lumen compromise. The widespread use of coronary stents has fundamentally altered the vascular response to injury by causing a more intense and prolonged inflammatory state.

Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury

“…The medium was then removed, and the dishes were washed twice with PBS before addition of 3 ml of warm (37°C) RPMI 1640 (Invitrogen) medium containing 10% FBS (Equitech-Bio Inc, Kerrville, TX) and a mixture of 100 U/ml penicillin-100 µg/ml streptomycin (Invitrogen). The plates were then incubated for 72 h at 37°C under a 5% CO 2 atmosphere, after which the macrophages were collected and analyzed by quantitative real-time RT-PCR.…”

“…Accumulating evidence now shows that inflammatory cell infiltration [2,3], proliferation/migration of vascular smooth muscle cells (VSMCs) [4,5], and deposition of extracellular matrix [6] all contribute to the pathogenesis of neointimal hyperplasia. Moreover, inflammatory cell infiltration of the neointima is intimately related to oxidative stress [7], and several lines of evidence indicate that NADPH oxidase plays a crucial role in the production of reactive oxygen species (ROS) within the neointima [8,9].…”

Preinterventional peak monocyte count and in-stent intimal hyperplasia after coronary stent implantation in human coronary arteries

“…20,21 Other animal studies have demonstrated that after stenting a particularly brisk early inflammatory response is induced with abundant surface adherent monocytes and granulocytes. 22 Several days and weeks later, macrophages invade the forming neointima and are observed clustering around stent struts. 22 Systemic inflammatory reaction may play a pivotal role in neointima formation within stent struts in addition to the local vessel wall injury, with the subsequent release of chemotactic and growth factors.…”

“…22 Several days and weeks later, macrophages invade the forming neointima and are observed clustering around stent struts. 22 Systemic inflammatory reaction may play a pivotal role in neointima formation within stent struts in addition to the local vessel wall injury, with the subsequent release of chemotactic and growth factors. 8,23 Fukuda et al 24 reported that the circulating monocyte count increased and reached its peak 2 days after stent implantation and that the maximum monocyte count after stent implantation showed a positive correlation with in-stent neointimal volume at 6-month follow-up.…”

Early Systemic Inflammatory Response to Drug-Eluting Stents Implantation: The Heart of the Difference?

“…Intracoronary stent deployment causes arterial wall trauma which elicits a local inflammatory wound-healing response to mechanical injury leading to an increase of inflammatory mediators in the target coronary artery segment [1]. Consequently, an early systemic inflammatory response is triggered, as observed by an almost immediate rise (within minutes after PCI) in systemic inflammatory markers, such as interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ).…”