title: TNF‑α regulates apoptosis of human vascular smooth muscle cells through gap junctions.
abstract: Inflammatory cytokines are released by immune cells and are able to induce vascular smooth muscle cells (VSMCs) to undergo apoptosis, causing atherosclerotic plaque rupture. Changes in the expression levels of connexins (Cxs) have been demonstrated in VSMCs to be involved in the pathogenesis of atherosclerotic progression. The present study examined the effect of tumor necrosis factor‑α (TNF‑α) on Cx43 expression levels and apoptosis in human VSMCs. Overexpression of Cx43 plasmids notably stimulated VSMC proliferation. TNF‑α directly inhibited Cx43 expression levels in a dose‑ and time‑dependent manner in VSMCs, however this was blocked by c‑Jun N‑terminal kinase inhibitor. TNF‑α also increased caspase‑3 activity and apoptosis of VSMCs through the inhibition of Cx43. These data suggested that TNF‑α induced the apoptosis of VMSCs and prompted the destabilization of atherosclerotic plaques by downregulating Cx43.
authors.affiliation: Infusion Preparation Center of Pharmacy Department, Xianning Central Hospital & The First Clinical Hospital of Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Tang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Xianning Central Hospital & The First Clinical Hospital of Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018031:Connexin 43; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3