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SUMO2 regulates vascular endothelial function and oxidative stress in mice
Journal article   Open access   Peer reviewed

SUMO2 regulates vascular endothelial function and oxidative stress in mice

Young-Rae Kim, Julia S Jacobs, Qiuxia Li, Ravinder Reddy Gaddam, Ajit Vikram, Jing Liu, Modar Kassan, Kaikobad Irani and Santosh Kumar
American journal of physiology. Heart and circulatory physiology, Vol.317(6), pp.H1292-H1300
12/01/2019
DOI: 10.1152/ajpheart.00530.2019
PMCID: PMC8906825
PMID: 31584834
url
https://doi.org/10.1152/ajpheart.00530.2019View
Published (Version of record) Open Access

Abstract

SUMOylation is a posttranslational modification of lysine residues. Modification of proteins by small ubiquitin-like modifiers (SUMO)1, -2, and -3 can achieve varied, and often unique, physiological and pathological effects. We looked for SUMO2-specific effects on vascular endothelial function. SUMO2 expression was upregulated in the aortic endothelium of hypercholesterolemic low-density lipoprotein receptor-deficient mice and was responsible for impairment of endothelium-dependent vasorelaxation in these mice. Moreover, overexpression of SUMO2 in aortas ex vivo, in cultured endothelial cells, and transgenically in the endothelium of mice increased vascular oxidative stress and impaired endothelium-dependent vasorelaxation. Conversely, inhibition of SUMO2 impaired physiological endothelium-dependent vasorelaxation in normocholesterolemic mice. These findings indicate that while endogenous SUMO2 is important in maintenance of normal endothelium-dependent vascular function, its upregulation impairs vascular homeostasis and contributes to hypercholesterolemia-induced endothelial dysfunction. Sumoylation is known to impair vascular function; however, the role of specific SUMOs in the regulation of vascular function is not known. Using multiple complementary approaches, we show that hyper-SUMO2ylation impairs vascular endothelial function and increases vascular oxidative stress, whereas endogenous SUMO2 is essential for maintenance of normal physiological function of the vascular endothelium.
 Animals Diet, High-Fat - adverse effects Endothelium, Vascular - metabolism Endothelium, Vascular - physiology Human Umbilical Vein Endothelial Cells - metabolism Humans Hypercholesterolemia - etiology Hypercholesterolemia - metabolism Male Mice Mice, Inbred C57BL Oxidative Stress Small Ubiquitin-Related Modifier Proteins - genetics Small Ubiquitin-Related Modifier Proteins - metabolism Vasodilation

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