Insulin induces PKC-dependent proliferation of mesenteric vascular smooth muscle cells from hypertensive patients

Background and objectives Proliferation of human vascular smooth muscle cells(VSMCs)induced by hyperinsulinemia is a very common clinical pathology.Extensive research has focused on PKC(Protein kinase C)-MAPK(mitogen-activated protein kinase)intracellular signal transduction and the phenotypic modulation accompanied by reorganization of intracellular F-actins in VSMCs.Methods DNA synthesis,signaling of ERK1/2 MAPKs,and changes inα-smooth muscle(SM)actin and F-actin were studied in hypertensive and normotensive human arterial VSMCs exposed to insulin and PMA with and without the PKC inhibitor,GF109203X.Results Differences among cell types in MAPK signaling,α-SM actin,and F-actin isoforms in VSMCs harvested from the arteries of patients with essential hypertension(EH)and normotension(NT)were identified in response to insulin treatment.Proliferation and activation of MAPK were more pronounced in EH VSMCs than in NEH VSMCs.Insulin exposure decreased expression ofα-SM actin and was accompanied by rearrangement of intracellular F-actins in VSMCs,especially in the EH group.These effects were reversed by treatment with the PKC inhibitor.Conclusions Human mesenteric VSMCs of EH and NT patients differed in proliferation,MAPK signaling,and degree of changes inα-SM actin and F-actin isoforms immediately following insulin exposure in vitro.

Biofunctionalized composite scaffold to potentiate osteoconduction,angiogenesis,and favorable metabolic microenvironment for osteonecrosis therapy

Osteonecrosis is a common orthopedic disease in clinic,resulting in joint collapse if no appropriate treatment is performed in time.Core decompression is a general treatment modality for early osteonecrosis.However,effective bone regeneration in the necrotic area is still a significant challenge.This study developed a biofunctionalized composite scaffold(PLGA/nHA30VEGF)for osteonecrosis therapy through potentiation of osteoconduction,angiogenesis,and a favorable metabolic microenvironment.The composite scaffold had a porosity of 87.7%and compressive strength of 8.9 MPa.PLGA/nHA30VEGF had an average pore size of 227.6μm and a water contact angle of 56.5◦with a sustained release profile of vascular endothelial growth factor(VEGF).After the implantation of PLGA/nHA30VEGF,various osteogenic and angiogenic biomarkers were upregulated by 2-9 fold compared with no treatment.Additionally,the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA30VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis.The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis.