Dietary salt initiates redox signaling between endothelium and vascular smooth muscle through NADPH oxidase 4

• Published in: Redox biology Vol. 52; p. 102296
• Main Authors: Ying, Kai er, Feng, Wenguang, Ying, Wei-Zhong, Li, Xingsheng, Xing, Dongqi, Sun, Yong, Chen, Yabing, Sanders, Paul W.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2022; Elsevier
• Subjects: Animals; Cell signaling; Core Binding Factor Alpha 1 Subunit - genetics; Dietary salt; Endothelium - metabolism; Endothelium, Vascular - metabolism; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Mice; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - metabolism; NADPH Oxidase 1 - metabolism; NADPH Oxidase 4 - genetics; NADPH Oxidase 4 - metabolism; NADPH Oxidases - metabolism; Osteogenesis; Oxidation-Reduction; Research Paper; Runx2; Sodium Chloride; Sodium Chloride, Dietary - metabolism; Vascular smooth muscle; Hydrogen peroxide; Dietary salt; PTEN; FoxO3a; PP2a; Vascular smooth muscle; Akt; H2O2; Cell signaling; BP; Pex14; PI3K; ANOVA; NOX4; TGF-β1; HUVEC; VSMC; Runx2; FoxO1
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2022.102296

Prevention of phenotype switching of vascular smooth muscle cells is an important determinant of normal vascular physiology. Hydrogen peroxide (H2O2) promotes osteogenic differentiation of vascular smooth muscle cells through expression of Runt related transcription factor 2 (Runx2). In this study, an increase in dietary NaCl increased endothelial H2O2 generation through NOX4, a NAD(P)H oxidase. The production of H2O2 was sufficient to increase Runx2, osteopontin and osteocalcin in adjacent vascular smooth muscle cells from control littermate mice but was inhibited in mice lacking endothelial Nox4. A vascular smooth muscle cell culture model confirmed the direct involvement of the activation of protein kinase B (Akt) with inactivation of FoxO1 and FoxO3a observed in the control mice on the high NaCl diet. The present study also showed a reduction of catalase activity in aortas during high NaCl intake. The findings demonstrated an interesting cell-cell communication in the vascular wall that was initiated with H2O2 production by endothelium and was regulated by dietary NaCl intake. A better understanding of how dietary salt intake alters vascular biology may improve treatment of vascular disease that involves activation of Runx2. [Display omitted] •A redox-mediated communication developed between the endothelium and vascular smooth muscle cells during increased dietary NaCl intake.•The effects of increased dietary NaCl intake on vascular smooth muscle cells were inhibited in mice that lacked Nox4 in endothelium.•Endothelial production of H2O2 recruited Akt, FoxO1, and FoxO3a in adjacent vascular smooth muscle cells to lower catalase and increase Runx2.•The observations occurred independently of changes in blood pressure.