Analysis of the correlations of hypertension complicated with or without hypertensive nephropathy with glucose and lipid metabolism, vascular endothelial function, inflammation, oxidative stress and course of disease

AbstractSalvia miltiorrhiza-Dalbergia odorifera coupled-herbs (SMDOCH) has been used to treat coronary heart disease (CHD) for thousands of years, but its unclear bioactive components and mechanisms greatly limit its clinical application. In this study, for the first time, we used network pharmacology to elucidate the mechanisms of action of SMDOCH on CHD. We collected 270 SMDOCH-related targets from 74 bioactive components and 375 CHD-related targets, with 58 overlapping common targets. Next, we performed enrichment analysis for common-target network and protein-protein interaction (PPI) network. The results showed that SMDOCH affected CHD mainly through 10 significant signaling pathways in three biological processes: ‘vascular endothelial function regulation’, ‘inflammatory response’, and ‘lipid metabolism’. Six pathways belonged to the ‘vascular endothelial function regulation’ model, which primarily regulated hormone (renin, angiotensin, oestrogen) activity, and included three key upstream pathways that influence vascular endothelial function, namely KEGG:04933, KEGG:05418, and KEGG:04066. Three pathways, namely KEGG:04668, KEGG:04064, and KEGG:04620, belonged to the ‘inflammatory response’ model. One pathway (KEGG:04920) belonged to the ‘lipid metabolism’ model. To some extent, this study revealed the potential bioactive components and pharmacological mechanisms of SMDOCH on CHD, and provided a new direction for the development of new drugs for the treatment of CHD.

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The effects of equal caloric high fat and western diet on metabolic syndrome, oxidative stress and vascular endothelial function in mice

Acta Physiologica ◽

10.1111/apha.12253 ◽

2014 ◽

Vol 211 (3) ◽

pp. 515-527 ◽

Cited By ~ 41

Author(s):

I. Heinonen ◽

P. Rinne ◽

S. T. Ruohonen ◽

S. Ruohonen ◽

M. Ahotupa ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Endothelial Function ◽

Western Diet ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

High Fat

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SUMO2 regulates vascular endothelial function and oxidative stress in mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00530.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. H1292-H1300 ◽

Cited By ~ 2

Author(s):

Young-Rae Kim ◽

Julia S. Jacobs ◽

Qiuxia Li ◽

Ravinder Reddy Gaddam ◽

Ajit Vikram ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Function ◽

Vascular Function ◽

Ex Vivo ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

Density Lipoprotein Receptor ◽

Vascular Oxidative Stress

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. NEW & NOTEWORTHY 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.

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