Function of connexin 43 and RhoA/LIMK2/Cofilin signaling pathway in transient changes of contraction and dilation of human umbilical arterial smooth muscle cells.

Abstract

BACKGROUND:

Post-induction hypotension, a common complication after propofol-based induction regimen, is a life-threatening challenge for anesthesiologists especially when unexpected pre-induction hypertension characterized by angiotensin release and increased vascular tone was presented by the same patient. Gap junctions (GJs) composed of connexin 43 (Cx43) have been considered a key factor in regulating vascular contraction and dilation. We aimed to explore the role of Cx43-GJs during peri-induction blood pressure fluctuation and elucidate the underlying mechanisms.

METHODS:

Human umbilical arterial smooth muscle cells (HUASMCs) were pretreated by short-term Angiotensin Ⅱ (Ang Ⅱ) with or without subsequent propofol treatment to simulate transient contraction and dilation of vascular smooth muscle cells during anesthesia induction. F-actin polymerization, a classic indicator of HUASMCs constriction, was determined by F-actin staining assay. Both the function and expression of Cx43-GJs during transient contraction and dilation of HUASMCs, and their potential regulation of downstream Ca2+/RhoA/LIMK2/Cofilin signaling pathway were explored via different targeting inhibitors and siRNAs.

RESULTS:

Ang Ⅱ pretreatment significantly induced F-actin polymerization that indicate cell contraction, accompanied by enhanced GJs function on HUASMCs. With the inhibition of Cx43 GJs by the specific inhibitor, Gap26, and Cx43-siRNA, Ang Ⅱ-induced F-actin polymerization was reversed accompanied with the decrease of intracellular Ca2+ mobility and the RhoA/LIMK2/Cofilin signaling pathway activity. We also noticed that propofol application could inhibit GJs function, the same as Gap26. Simultaneously, intracellular Ca2+ mobility and RhoA/LIMK2/Cofilin signaling pathway activity on HUASMCs were both downregulated, finally resulting in downstream reduction of F-actin polymerization.

CONCLUSION:

The function of Cx43-GJs lies in the center of Ang Ⅱ-induced contraction of HUASMCs, which potentially regulates intracellular Ca2+ mobility as well as RhoA/LIMK2/Cofilin signaling pathway activity. Propofol can reverse this effect induced by Ang Ⅱ through suppressing the function of Cx43-GJs.

• Authors: Zhizhao Deng, Yanling Zhang, Qian Zhang, Xianlong Li, Weiqi Zeng, Cai Jun, Dongdong Yuan
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 153 Pg. 106326 (12 2022) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 36330887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Connexin 43
• Actin Depolymerizing Factors
• Actins
• Propofol
• Angiotensin II
• RHOA protein, human
• rhoA GTP-Binding Protein
• LIMK2 protein, human
• Lim Kinases

Topics

• Humans
• Connexin 43 (genetics, metabolism)
• Actin Depolymerizing Factors (metabolism)
• Actins (metabolism)
• Propofol (metabolism, pharmacology)
• Dilatation
• Myocytes, Smooth Muscle (metabolism)
• Signal Transduction
• Angiotensin II (pharmacology, metabolism)
• rhoA GTP-Binding Protein (metabolism)
• Lim Kinases (metabolism)