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.

The Impact of Uremic Toxins on Vascular Smooth Muscle Cell Function

“…In vitro, inhibition of NFkB activation induced TNFα–mediated caspase-3 activity [ 67 ], increased the TNF-α-induced expression of p73β [ 69 ] (a pro-apoptotic protein that favors the expression of p53 target genes (such as p21) and is involved in plaque progression and rupture), and promoted VSMC apoptosis. Furthermore, the TNF-α induced downregulation of Cx43 induced VSMC apoptosis in vitro [ 70 ]. A combination of IFN-γ, TNF-α, and IL-1β induced the apoptosis of cultured human and rat VSMCs through activation of the L-arginine/NOS pathway [ 71 ].…”

Exercise improves high fat diet-impaired vascular function

“…The genes associated with expression of pro-inflammatory cytokines were examined by (RT-qPCR) (11). Total RNA was isolated from the aortae using RNAzol (Sigma-Aldrich; Merck KGaA) and cDNA synthesis was completed by using 1 µg total RNA with 5X reaction buffer, oligo(dT) (1 µg), RNAse inhibitor, MgCl 2 , dNTP mix, and ImProm II reverse transcriptase as per the ImProm II reverse transcription kit (cat.…”

The Role of Connexin-43 in the Inflammatory Process: A New Potential Therapy to Influence Keratitis

“…Then, IL-1 β decreases Cx43 expression, which can be mediated via the ERK-MAPK signaling pathway [43]. In vascular smooth muscle cells, IL-1 β inhibits the expression level of Cx43 [57]. TNF- α , another important inflammatory cytokine, participates in the regulation of Cx43 levels.…”

“…TNF- α , another important inflammatory cytokine, participates in the regulation of Cx43 levels. During inflammation in vascular smooth muscle cells, TNF- α directly inhibits Cx43 via the JNK pathway, which leads to apoptosis of vascular smooth muscle cells [57]. The Cx43 formed GJ in DCs, while TNF- α combined with IL-1 β could advance the GJ communication [30].…”