New Targets For Vascular Remodeling: Evaluating The Role Of Sulfated Glycosaminoglycans In The Prevention Of In-Stent Restenosis (Literature Review)
Abstract
Percutaneous coronary intervention (PCI) with stenting is the cornerstone of revascularization in ischemic heart disease. However, in-stent restenosis (ISR), a pathobiological response to vascular injury, remains a significant limitation, affecting a substantial subset of patients and necessitating repeat interventions. This review aims to critically analyze the multifactorial pathogenesis of ISR, focusing on the pivotal roles of inflammation, smooth muscle cell (SMC) phenotype switching, and extracellular matrix (ECM) dysregulation. Moving beyond conventional anti-proliferative strategies, we explore a novel pathogenetic approach centered on the pleiotropic properties of specific sulfated glycosaminoglycans (GAGs)—chondroitin sulfate (CS) and glucosamine sulfate (GS). Traditionally used in osteoarthritis management, these molecules exhibit potent anti-inflammatory, anti-thrombotic, and ECM-modulating effects relevant to vascular pathophysiology. We synthesize evidence from molecular, experimental, and early clinical studies suggesting that CS/GS can inhibit key drivers of ISR, such as versican-CD44-mediated signaling and NF-κB activation. The review also discusses the importance of pharmaceutical-grade purity for clinical translation and positions this approach within the evolving landscape of adjunctive pharmacotherapy for PCI, highlighting its potential to improve long-term vascular patency and patient outcomes.