Vascular smooth muscle cells in intimal hyperplasia, an update

Abstract

Arterial occlusive disease is the leading cause of death in Western countries. Core contemporary therapies for this disease include angioplasties, stents, endarterectomies and bypass surgery. However, these treatments suffer from high failure rates due to re-occlusive vascular wall adaptations and restenosis. Restenosis following vascular surgery is largely due to intimal hyperplasia. Intimal hyperplasia develops in response to vessel injury, leading to inflammation, vascular smooth muscle cells dedifferentiation, migration, proliferation and secretion of extra-cellular matrix into the vessel’s innermost layer or intima. In this review, we describe the current state of knowledge on the origin and mechanisms underlying the dysregulated proliferation of vascular smooth muscle cells in intimal hyperplasia, and we present the new avenues of research targeting VSMC phenotype and proliferation.

Perivascular CLICK‐gelatin delivery of thrombospondin‐2 small interfering RNA decreases development of intimal hyperplasia after arterial injury

“…TSP‐2, which is primarily produced by SMC and fibroblasts, has been described to be an important modulator of cell‐matrix interactions and regulator of SMC and EC proliferation 27,36 . TSP‐2 role in increasing SMC proliferation, a key step in the formation of IH, has been clearly described 37,38 . Our study suggested that the downregulation of TSP‐2 inhibits this dysregulated proliferation of cells, as demonstrated by the decrease of Ki‐67 in CCA treated with CLICK‐gelatin + TSP‐2 siRNA.…”

“…27,36 TSP-2 role in increasing SMC proliferation, a key step in the formation of IH, has been clearly described. 37,38 Our study suggested that the downregulation of TSP-2 inhibits this dysregulated proliferation of cells, as demonstrated by the decrease of Ki-67 in CCA treated with CLICK-gelatin + TSP-2 siRNA. Further supporting inhibition of cell proliferation as an important mechanism of TSP-2 downregulation in attenuating IH formation.…”

Integrated single-nuclei and spatial transcriptomic analysis reveals propagation of early acute vein harvest and distension injury signaling pathways following arterial implantation

“…Importantly, migration of fibroblasts to the intima plays a well-documented role in the development of intimal hyperplasia and atherosclerosis. 59 Within the intima of distended veins, myeloid cells are also enriched, further underscoring the recruitment and infiltration of immune cells initiated by the effects of distension on the endothelium. Lastly, SMCs display increased enrichment in the adventitia of distended veins, supporting our hypothesis that while the overall proportion of SMCs decreases following distension, SMCs present in the distended veins may undergo VSMC-reprogramming toward a synthetic phenotype facilitating their migration to the adventitia.…”

Nanotechnology in development of next generation of stent and related medical devices: Current and future aspects

“…This is due to their composition, which includes polymer cores and lipid/lipid‐PEG shells (Hadinoto et al, 2013) (Figure 3d). Intimal hyperplasia and a high level of lipid and platelet adhesion following localized injury caused by the stent can be counteracted by a prohealing, noncytotoxic remodeling approach for the repression of SMC lipid uptake and hyperproliferation, which could be effective in preventing further oxidative stress, SMC proliferation, and platelet adhesion within stented arteries (Chan et al, 2016; Déglise et al, 2022). Chan et al reported that the lipid hybrid NP‐based therapy causes effective vascular targeting and controlled drug release.…”