Beneficial effect of simvastatin on human umbilical vein endothelial cells gap junctions induced by TNF-α

Abstract

Although simvastatin has been shown to inhibit vascular permeability, which might be amplified via gap junction intercellular communication (GJIC), the underlying mechanism of action remains unclear. In the present study, we investigated the effects and mechanisms of simvastatin on endothelial cells GJIC. Specifically, human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α (10 ng/mL) alone or in combination with simvastatin (5 µM), and their effects on vascular endothelial cell GJIC tested via the scrape loading/dye transfer (SL/DT) assay. Next, we performed immunofluorescence, real-time PCR and western blot assays to analyze expression of Cx37, Cx40 and Cx43 in HUVECs. Results showed that GJIC activity in HUVECs was markedly elevated in HUVECs treated with TNF-α in combination with simvastatin. In addition, simvastatin treatment significantly upregulated expression of Cx37 and Cx40 but downregulated Cx43 mRNAs and proteins. Taken together, these marked changes indicated that simvastatin exerts its regulatory effects on gap junction function by upregulating Cx37 and Cx40 and downregulating Cx43 expression.

Mangifera Indica leaf extracts promote hair growth via activation of Wnt signaling pathway in human dermal papilla cells

“…Total RNA was extracted from HFDP cells using a Hybrid-R™ Kit (GeneAll, Seoul, Korea) according to the manufacturer’s instructions (Ling et al 2022 ). cDNA was synthesized using M-MLV reverse transcriptase (Promega) and random hexamers.…”

Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function

“…Then, oxidized low-density lipoprotein (ox-LDL) induced an increase in Cx43, JAM-A, and VEcadherin protein expression [158]. In addition, statin drug Simvastatin suppresses the TNFα-induced inhibition of GJ channels' activity in an in vitro ECs model, using HUVEC, by upregulating Cx37 and Cx40 expression but downregulating Cx43 [199]. Moreover, in line with leucocyte-ECs interactions, in a hamster cheek pouch, the TNF-α inflammatory effect on leucocyte adhesion is suppressed in ECs Cx43-deficient mice as well as by a pharmacological blockade of GJ [200]; thus, Cx43 is predominantly involved in atherosclerosis-related leucocyte adhesion, this is consistent with its contribution to hyperpermeability.…”