Contribution of Nrf2 to Atherogenic Phenotype Switching of Coronary Arterial Smooth Muscle Cells Lacking CD38 Gene

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Ming XuPin-Lan Li

Abstract

Recent studies have indicated that CD38 gene deficiency results in dedifferentiation or transdifferentiation of arterial smooth muscle cells upon atherogenic stimulations. However, the molecular mechanisms mediating this vascular smooth muscle (SMC) phenotypic switching remain unknown. Methods & In the present study, we first characterized the phenotypic change in the primary cultures of coronary arterial myocytes (CAMs) from CD38-/- mice. It was shown that CD38 deficiency decreased the expression of contractile marker calponin, SM22α and α-SMA but increased the expression of SMC dedifferentiation marker, vimentin, which was accompanied by enhanced cell proliferation. This phenotypic change in CD38-/- CAMs was enhanced by 7-ketocholesterol (7-Ket), an atherogenic stimulus. We further found that the CD38 deficiency decreased the expression and activity of nuclear factor E2-related factor 2 (Nrf2), a basic leucine zipper (bZIP) transcription factor sensitive to redox regulation. Similar to CD38 deletion, Nrf2 gene silencing increased CAM dedifferentiation upon 7-Ket stimulation. In contrast, the overexpression of Nrf2 gene abolished 7-Ket-induced dedifferentiation in CD38-/- CAMs. Given the sensitivity of Nrf2 to oxidative st...Continue Reading

Citations

Dec 13, 2016·Pharmacology & Therapeutics·Deepak A DeshpandeMathur S Kannan
Mar 30, 2018·Cardiovascular Research·Gillian DouglasKeith M Channon
Apr 28, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Witold N NowakQingbo Xu
Nov 22, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Xinxu YuanPin-Lan Li
May 31, 2020·Cardiovascular Drugs and Therapy·Wanyun ZuoQiming Liu
Apr 30, 2019·Frontiers in Pharmacology·Rafael M da CostaRita C Tostes
Feb 19, 2021·Antioxidants & Redox Signaling·Sarah Hartwick Bjorkman, Renata Oliveira Pereira
May 1, 2021·Antioxidants·David Sánchez-InfantesMaría Galán
Sep 1, 2018·Vascular Pharmacology·Damian KloskaAnna Grochot-Przeczek

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Methods Mentioned

BETA
electrophoresis
X-ray
Assay
transcription factor assay
ESR
flow cytometry
transfection
gene knockout
nuclear translocation

Software Mentioned

Metafluor
Image J
Universal

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