Thermogelling PLGA-PEG-PLGA from PolySciTech used in development of cardiovascular gel

 

Cardiovascular disease remains one of the leading causes of death. A popular treatment is angioplasty to widen a blocked artery however, it is common afterwards for the blood-vessel to regrow in and reduce the flow of blood through the vessel. Recently, researchers at The Ohio State University, University of Virginia, and University of Wisconsin–Madison used PLGA-PEG-PLGA (AK012) from PolySciTech (www.polyscitech.com) to create a gel for delivery of medicinal molecules to reduce restenosis. Read more: Wang, Bowen, Mengxue Zhang, Go Urabe, Takuro Shirasu, Lian-Wang Guo, and K. Craig Kent. "PERK Inhibition Promotes Post-angioplasty Re-endothelialization via Modulating SMC Phenotype Changes." Journal of Surgical Research 257: 294-305. https://www.sciencedirect.com/science/article/pii/S0022480420303450

“Abstract: Background: Drug-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 kinase (PERK) effectively mitigated both restenosis and thrombosis in rodent models. This motivated us to determine how PERK inhibition impacts re-endothelialization. Methods: Re-endothelialization was evaluated in endothelial-denuded rat carotid arteries after balloon angioplasty and periadventitial administration of PERK inhibitor in a hydrogel. To study whether PERK in smooth muscle cells (SMCs) regulates re-endothelialization by paracrinally influencing endothelial cells (ECs), denuded arteries exposing SMCs were lentiviral-infected to silence PERK; in vitro, the extracellular vesicles isolated from the medium of PDGF-activated, PERK-upregulating human primary SMCs were transferred to human primary ECs. Results: Treatment with PERK inhibitor versus vehicle control accelerated re-endothelialization in denuded arteries. PERK-specific silencing in the denuded arterial wall (mainly SMCs) also enhanced re-endothelialization compared to scrambled shRNA control. In vitro, while medium transfer from PDGF-activated SMCs impaired EC viability and increased the mRNA levels of dysfunctional EC markers, either PERK inhibition or silencing in donor SMCs mitigated these EC changes. Furthermore, CXCL10, a paracrine cytokine detrimental to ECs, was increased by PDGF activation and decreased after PERK inhibition or silencing in SMCs. Conclusions: Attenuating PERK activity pharmacologically or genetically provides an approach to accelerating post-angioplasty re-endothelialization in rats. The mechanism may involve paracrine factors regulated by PERK in SMCs that impact neighboring ECs. This study rationalizes future development of PERK-targeted endothelium-friendly vascular interventions. Keywords: Re-endothelialization Angioplasty Smooth muscle cell Endothelial cell PERK”