PERK Inhibition Promotes Post-angioplasty Re-endothelialization via Modulating SMC Phenotype Changes

BackgroundDrug-eluting stents impair post-angioplasty re-endothelialization thus compromising restenosis prevention while heightening thrombotic risks. We recently found that inhibition of protein kinase RNA-like endoplasmic reticulum (PERK) effectively mitigated both and thrombosis in rodent models. This motivated us to determine how PERK impacts re-endothelialization.MethodsRe-endothelialization was evaluated endothelial-denuded rat carotid arteries after balloon angioplasty periadventitial administration inhibitor a hydrogel. To study whether smooth muscle cells (SMCs) regulates by paracrinally influencing endothelial (ECs), denuded exposing SMCs were lentiviral-infected silence PERK; vitro, the extracellular vesicles isolated from medium PDGF-activated, PERK-upregulating human primary transferred ECs.ResultsTreatment with versus vehicle control accelerated arteries. PERK-specific silencing arterial wall (mainly SMCs) also enhanced compared scrambled shRNA control. In transfer PDGF-activated impaired EC viability increased mRNA levels dysfunctional markers, either or donor these changes. Furthermore, CXCL10, paracrine cytokine detrimental ECs, PDGF activation decreased SMCs.ConclusionsAttenuating activity pharmacologically genetically provides an approach accelerating rats. The mechanism may involve factors regulated impact neighboring ECs. rationalizes future development PERK-targeted endothelium-friendly vascular interventions.