scholarly journals SUMO2 regulates vascular endothelial function and oxidative stress in mice

2019 ◽  
Vol 317 (6) ◽  
pp. H1292-H1300 ◽  
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.

scholarly journals Plasma norepinephrine is an independent predictor of vascular endothelial function with aging in healthy women

2011 ◽  
Vol 111 (5) ◽  
pp. 1416-1421 ◽  
Author(s):  
Rachelle E. Kaplon ◽  
Ashley E. Walker ◽  
Douglas R. Seals
Keyword(s):  
Endothelial Function ◽  
Sympathetic Activity ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasma Norepinephrine ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Key Factor

We tested the hypothesis that reductions in vascular endothelial function (endothelium-dependent dilation, EDD) with age are related to increases in sympathetic activity. Among 314 healthy men and women, age was inversely related to brachial artery flow-mediated dilation (FMD) ( r = −0.30, P < 0.001), a measure of EDD, and positively related to plasma norepinephrine concentrations (PNE), a marker of sympathetic activity ( r = 0.49, P < 0.001). Brachial FMD was inversely related to PNE in all subjects ( r = −0.25, P < 0.001) and in men ( n = 187, r = −0.17, P = 0.02) and women ( n = 127, r = −0.37, P < 0.001) separately. After controlling for PNE (multiple regression analysis), brachial FMD remained significantly related to age in all subjects ( r = −0.20, P < 0.001) and in men ( r = −0.23, P < 0.01), but not women ( r = −0.16, P = 0.06). Consistent with this, brachial FMD remained significantly related to PNE when controlling for age ( r = −0.24, P < 0.01) and menopause status ( r = −0.24, P < 0.01) in women. Indeed, PNE was the strongest independent correlate of brachial FMD in women after controlling for conventional cardiovascular disease risk factors ( r = −0.22, P = 0.01). This relation persisted in a subset of women ( n = 113) after further accounting for the effects of plasma oxidized low-density lipoprotein ( P < 0.05), a circulating marker of oxidative stress. Endothelium-independent dilation was not related to age in either men or women ( P > 0.05). These results provide the first evidence that EDD is inversely related to sympathetic activity, as assessed by PNE, among healthy adults varying in age. In particular, our findings suggest that sympathetic nervous system activity may be a key factor involved in the modulation of vascular endothelial function with aging in women.

scholarly journals Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Kevin D. Ballard ◽  
Eunice Mah ◽  
Yi Guo ◽  
Richard S. Bruno ◽  
Beth A. Taylor ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Plasma Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Ldl Apheresis ◽  
Nitrative Stress ◽  
Artery Flow

Objective. To investigate vascular endothelial function (VEF) responses to a single low-density lipoprotein (LDL) apheresis session in hypercholesterolemic patients undergoing chronic treatment.Methods. We measured brachial artery flow-mediated dilation (FMD), plasma lipids, vitamin E (α- andγ-tocopherol), markers of oxidative/nitrative stress (malondialdehyde (MDA) and nitro-γ-tocopherol (NGT)), and regulators of NO metabolism (arginine (ARG) and asymmetric dimethylarginine (ADMA)) prior to (Pre) and immediately following (Post) LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y).Results. Relative to Pre, total cholesterol (7.8±1.5 mmol/L) and LDL-cholesterol (6.2±1.2 mmol/L) were 61% and 70% lower (P<0.01), respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6%) and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasmaα-tocopherol,γ-tocopherol, and NGT concentrations were 52–69% lower at Post (P<0.01), andα-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3.Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia.

scholarly journals Aging and vascular endothelial function in humans

2011 ◽  
Vol 120 (9) ◽  
pp. 357-375 ◽  
Author(s):  
Douglas R. Seals ◽  
Kristen L. Jablonski ◽  
Anthony J. Donato
Keyword(s):  
Oxidative Stress ◽  
Endothelial Function ◽  
Vascular Inflammation ◽  
Dietary Factors ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Antioxidant Defences ◽  
Effective Strategies ◽  
Glycation End Products ◽  
Vascular Oxidative Stress

Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging.

Alterations in vascular function by syncytiotrophoblast extracellular vesicles via lectin-like oxidized low-density lipoprotein receptor-1 in mouse uterine arteries

2018 ◽  
Vol 132 (21) ◽  
pp. 2369-2381 ◽  
Author(s):  
Floor Spaans ◽  
Anita Quon ◽  
Stewart R. Rowe ◽  
Jude S. Morton ◽  
Raven Kirschenman ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Extracellular Vesicles ◽  
Vascular Function ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Oxidized Low Density Lipoprotein ◽  
Uterine Arteries ◽  
Density Lipoprotein Receptor

Syncytiotrophoblast extracellular vesicles (STBEVs), released into the maternal circulation during pregnancy, have been shown to affect vascular function; however, the mechanism remains unknown. In rats, STBEVs were shown to reduce endothelium-mediated vasodilation via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a multi-ligand scavenger receptor that has been associated with vascular dysfunction. Recently, LOX-1 was shown to interact with the angiotensin II type 1 receptor (AT-1). We hypothesized that, in pregnant mice, STBEVs would impair vascular function via LOX-1 and would specifically affect angiotensin II responses. Uterine arteries from pregnant control (C57BL/6) and LOX-1 knockout (LOX-1KO) mice were isolated on gestational day (GD) 18.5. Endothelium-dependent (methylcholine (MCh); ± N(G)-Nitro-L-arginine methyl ester to assess nitric oxide (NO) contribution), and -independent (sodium nitroprusside) vasodilation, and vasoconstriction (angiotensin II; ± AT-1 [candesartan] or angiotensin II type 2 receptor (AT-2) [PD123.319] receptor antagonists; high potassium salt solution) responses were assessed using wire myography. AT-1 and AT-2 expression was analyzed using fluorescence microscopy. Human umbilical vein endothelial cells (HUVECs) were stimulated with STBEVs ± LOX-1 blocking antibody, and superoxide and peroxynitrite production were analyzed. Although MCh-induced vasodilation was decreased (P=0.0012), NO contribution to vasodilation was greater in LOX-1KO mice (P=0.0055). STBEVs delayed angiotensin II tachyphylaxis in arteries from control but not LOX-1KO mice (P<0.0001), while AT-1 and AT-2 expression was unchanged. STBEVs increased peroxynitrite production in HUVECs via LOX-1 (P=0.0091). In summary, LOX-1 deletion altered endothelium-mediated vasodilation, suggesting that LOX-1 contributes to vascular adaptations in pregnancy. STBEVs increased angiotensin II responsiveness and oxidative stress levels via LOX-1, suggesting that increased LOX-1 expression/activation or STBEVs could adversely affect vascular function and contribute to vascular complications of pregnancy.

scholarly journals Effect of Strawberry Intake for 4 Weeks on Vascular Endothelial Function and Blood Pressure in Adults with Moderate Hypercholesterolemia (P06-128-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Di Xiao ◽  
Leailin Huang Huang ◽  
Indika Edirisinghe ◽  
Britt Burton-Freeman
Keyword(s):  
Blood Pressure ◽  
Endothelial Function ◽  
Vascular Function ◽  
Daily Intake ◽  
Random Order ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Freeze Dried ◽  
Pressure Independent ◽  
Hs Crp

Abstract Objectives The aim of this study is to investigate the effect of chronic strawberry intake on cardiovascular risk factors including fasting lipids concentrations, vascular endothelial function and blood pressure in middle-age overweight or obese individuals with moderate hypercholesterolemia. We hypothesized that 4-week strawberry intake would improve the lipids profile and concomitantly improve measures of vascular function. Methods In this randomized, double-blinded, controlled, crossover trial, thirty-four subjects (age 53 ± 1 years, BMI 31 ± 1 kg m-2, mean ± SD) consumed a strawberry beverage containing 25 gram freeze-dried strawberry powder or energy-matched control beverage in random order twice a day for 4 weeks. Treatment periods were separated by 4-week washout period. Fasting lipids, glucose, insulin, high sensitive c-reactive protein (hs-CRP), and postprandial flow-mediated dilation (FMD) and blood pressure, were measured at weeks 0, 4, 8 and 12. Results Fasting lipids, glucose, insulin, and hs-CRP did not differ between strawberry and control beverage interventions. In contrast, vascular function as measured by change in %FMD was significantly increased after strawberry compared to control after 4 weeks supplementation (4.3 ± 0.3% versus 3.6 ± 0.3%, respectively, p = 0.0096). In addition, %FMD was acutely increased from 0 to 1 hour after consuming strawberry beverage (p < 0.0001), which was consistent with reduced meal-induced increases in systolic blood pressure (SBP) postmeal (mean 2 hour changes in SBP after strawberry compared to control beverage, 2.3 ± 0.4 versus 3.4 ± 0.4 mmHg, p = 0.048). Conclusions Daily intake of strawberries may improve endothelial function and acute changes in blood pressure, independent of other metabolic changes, and may be considered a specific food/fruit to include in a heart-healthy diet in overweight or obese subjects with moderate hypercholesterolemia. Funding Sources California Strawberry Commission, Watsonville, CA, USA. Supporting Tables, Images and/or Graphs

scholarly journals Effects of combined use of atorvastatin and losartan in treating patients with diabetic nephropathy

2018 ◽  
Vol 16 ◽  
pp. 205873921879670
Author(s):  
Chao Ding ◽  
Xiaohua Hu
Keyword(s):  
Diabetic Nephropathy ◽  
Endothelial Function ◽  
Cardiovascular Events ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Inflammatory Factors ◽  
Control Group ◽  
Vascular Endothelial ◽  
Observation Group ◽  
Vascular Endothelial Function

This study is to investigate the effect of atorvastatin combined with losartan on inflammatory factors, vascular endothelial function, and cardiovascular events in patients with diabetic nephropathy. A total of 128 patients with diabetic nephropathy treated in our hospital from January 2014 to December 2015 were selected as the study subjects, and 64 cases were randomly divided into observation group and 64 cases in the control group. The control group was treated with losartan on the basis of routine treatment, and the observation group was treated with atorvastatin on the basis of the control group. The blood lipid, inflammatory factors, changes in vascular endothelial function and cardiovascular events were compared between the two groups. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were not significantly different between the two groups before treatment ( P > 0.05); after treatment, the levels of TC, TG, and LDL-C in the observation group were significantly lower than those of the control group, and the level of HDL-C was significantly higher than that of the control group ( P < 0.05). The levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) were not statistically different between the two groups before treatment ( P > 0.05); after treatment, the levels of hs-CRP, TNF-α, and IL-6 in the observation group were significantly lower than those of the control group ( P < 0.05), the level of HDL-C was significantly higher than that of the control group ( P < 0.05). There were no significant differences in the levels of endothelin-1 (ET-1) and nitric oxide (NO) between the two groups before treatment ( P > 0.05). After treatment, the level of ET-1 in the observation group was significantly lower than that of the control group ( P < 0.05), and the level of NO was significantly higher than that of the control group ( P < 0.05). After treatment, all patients were followed up for 2 years, and the incidence of secondary cardiovascular events in the observation group was 12.50% (8/64), which was significantly lower than 29.69% (19/64) of the control group ( P < 0.05). Combination of atorvastatin and losartan can significantly improve the levels of blood lipid, inflammatory factors, and vascular endothelial function in patients with diabetic nephropathy and can effectively reduce the incidence of cardiovascular events.

Sign in / Sign up

Export Citation Format

Share Document