scholarly journals High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging

2021 ◽  
Vol 8 (12) ◽  
pp. 173
Author(s):  
Iveta Nejmanová ◽  
Barbora Vitverová ◽  
Samira Eissazadeh ◽  
Katarina Tripská ◽  
Ivone Cristina Igreja Sa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Type Ii Diabetes Mellitus ◽  
Pharmacological Intervention ◽  
Control Group ◽  
Chow Diet ◽  
Soluble Endoglin ◽  
Atherosclerosis Development

Endoglin is a 180 kDa transmembrane glycoprotein that was demonstrated to be present in two different endoglin forms, namely membrane endoglin (Eng) and soluble endoglin (sEng). Increased sEng levels in the circulation have been detected in atherosclerosis, arterial hypertension, and type II diabetes mellitus. Moreover, sEng was shown to aggravate endothelial dysfunction when combined with a high-fat diet, suggesting it might be a risk factor for the development of endothelial dysfunction in combination with other risk factors. Therefore, this study hypothesized that high sEng levels exposure for 12 months combined with aging (an essential risk factor of atherosclerosis development) would aggravate vascular function in mouse aorta. Male transgenic mice with high levels of human sEng in plasma (Sol-Eng+) and their age-matched male transgenic littermates that do not develop high soluble endoglin (Control) on a chow diet were used. The aging process was initiated to contribute to endothelial dysfunction/atherosclerosis development, and it lasted 12 months. Wire myograph analysis showed impairment contractility in the Sol-Eng+ group when compared to the control group after KCl and PGF2α administration. Endothelium-dependent responsiveness to Ach was not significantly different between these groups. Western blot analysis revealed significantly decreased protein expression of Eng, p-eNOS, and ID1 expression in the Sol-Eng+ group compared to the control group suggesting reduced Eng signaling. In conclusion, we demonstrated for the first time that long-term exposure to high levels of sEng during aging results in alteration of vasoconstriction properties of the aorta, reduced eNOS phosphorylation, decreased Eng expression, and altered Eng signaling. These findings suggest that sEng can be considered a risk factor for the development of vascular dysfunction during aging and a potential therapeutical target for pharmacological intervention.

Inflammation and Microvascular and Macrovascular Endothelial Dysfunction in Rheumatoid Arthritis: Effect of Treatment

2010 ◽  
Vol 37 (4) ◽  
pp. 711-716 ◽  
Author(s):  
WILL FOSTER ◽  
DAVID CARRUTHERS ◽  
GREGORY Y.H. LIP ◽  
ANDREW D. BLANN
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Venous Blood ◽  
Microvascular Function ◽  
Control Group ◽  
Antirheumatic Therapy ◽  
Antiinflammatory Therapy ◽  
Patients With Diabetes ◽  
Plasma Markers

Objective.To determine whether abnormalities in microvascular and macrovascular function in rheumatoid arthritis (RA) are associated with plasma markers [von Willebrand factor (VWF)] of endothelial dysfunction and inflammation [C-reactive protein (CRP)] and whether the abnormalities would be altered by treatment. Endothelial dysfunction and inflammation in RA may contribute to adverse cardiovascular events. Although endothelial dysfunction in RA has been demonstrated by altered plasma markers, the relationships with macrovascular and microvascular function are relatively unexplored.Methods.We recruited 66 patients with chronic RA, 48 community controls (CC), and 25 patients with diabetes and hypertension as a disease control group (DC). Subjects had venous blood sampled for plasma markers, and underwent laser Doppler perfusion imaging of forearm skin (to assess microvascular circulation) following acetylcholine and sodium nitroprusside iontophoresis, to assess endothelium-dependent and endothelium-independent responses, respectively. Brachial artery flow-mediated dilatation assessed endothelial dysfunction in a macrovascular bed. A subgroup of 29 patients with RA were assessed pretherapy and after 2–4 weeks of antirheumatic therapy.Results.As expected, patients with RA had higher CRP, erythrocyte sedimentation rate (ESR), and VWF. Endothelium-independent vasoreactivity was abnormal in RA, and this correlated negatively with CRP. All aspects of microvascular function were abnormal in the DC compared to the CC. Macrovascular function was preserved in RA but was abnormal in the DC group. Four weeks of antiinflammatory therapy reduced CRP and ESR but had no effect on any vascular function index in the patients with RA.Conclusion.Patients with RA have abnormal endothelium-independent microvascular function that correlates with inflammation but is not altered by short-term antiinflammatory therapy.

scholarly journals Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Satomi Kagota ◽  
Kana Maruyama ◽  
John J. McGuire
Keyword(s):  
Systematic Review ◽  
Metabolic Syndrome ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Cell Surface Receptor ◽  
Metabolic Dysfunction ◽  
The Face ◽  
Surface Receptor ◽  
Treatment Of Obesity

Proteinase-activated receptor 2 (PAR2) is a cell surface receptor activated by serine proteinases or specific synthetic compounds. Interest in PAR2 as a pharmaceutical target for various diseases is increasing. Here we asked two questions relevant to endothelial dysfunction and diabetes: How is PAR2 function affected in blood vessels? What role does PAR2 have in promoting obesity, diabetes, and/or metabolic syndrome, specifically via the endothelium and adipose tissues? We conducted a systematic review of the published literature in PubMed and Scopus (July 2015; search terms: par2, par-2, f2lr1, adipose, obesity, diabetes, and metabolic syndrome). Seven studies focused on PAR2 and vascular function. The obesity, diabetes, or metabolic syndrome animal models differed amongst studies, but each reported that PAR2-mediated vasodilator actions were preserved in the face of endothelial dysfunction. The remaining studies focused on nonvascular functions and provided evidence supporting the concept that PAR2 activation promoted obesity. Key studies showed that PAR2 activation regulated cellular metabolism, and PAR2 antagonists inhibited adipose gain and metabolic dysfunction in rats. We conclude that PAR2 antagonists for treatment of obesity indeed show early promise as a therapeutic strategy; however, endothelial-specific PAR2 functions, which may offset mechanisms that produce vascular dysfunction in diabetes, warrant additional study.

Abstract 21: Retinol-binding Protein 7 (RBP7), a Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Target Gene, is a Novel Regulator of Endothelial Function

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Chunyan Hu ◽  
Ko-Ting Lu ◽  
Mary L Modrick ◽  
Silke Vogel ◽  
Frank M Faraci ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Target Gene ◽  
Binding Protein ◽  
Dominant Negative ◽  
Retinol Binding Protein ◽  
Nitric Oxide Donor ◽  
Chow Diet ◽  
Protective Effects ◽  
Fatty Acid Binding

PPARG, a ligand-activated transcription factor, in the endothelium regulates vascular function and blood pressure, through mechanisms that remain poorly defined. Endothelial-specific expression of dominant negative (DN) PPARG (E-V290M) caused endothelial dysfunction when combined with a high fat diet (HFD). RBP7 is an intracellular retinoid binding protein belonging to the family of fatty acid-binding proteins and a PPARG target gene. RBP7 expression in aorta is induced by rosiglitazone and repressed by DN PPARG, and its level of expression is highly correlated with PPARG in other tissues. RBP7 is also expressed in endothelium. We hypothesize that RBP7 may mediate some vascular protective effects of PPARG during HFD. We examined vascular responses in basilar artery (BA, pressurized myograph) and carotid artery (CA, wire myograph) of RBP7-deficient (KO), heterozygous (HZ), and wild type (WT) mice fed normal chow diet (ND) or HFD for 8 or 20 wks. Weight gain was similar in all three HFD-fed groups and was higher than ND-fed mice. There was no difference in the endothelium-dependent, acetylcholine (ACh)-induced relaxation in either BA or CA of any group under ND. Following 8 wks HFD, BA from KO mice exhibited impaired relaxation to ACh compared to control mice (at 100μM: 33±7% KO vs 73±7% HZ vs 83±10% WT, p<0.05). A normal response was observed to the nitric oxide donor, nitroprusside (SNP). An impaired ACh-, but not SNP- or papaverine-induced relaxation was observed in CA of KO mice after 20 wks of HFD (ACh 30μM: 49±6% KO vs 61±3% HZ vs 70±4% WT, p<0.05). No differences were found in phenylephrine- and endothelin-1-induced contractions in CA in any group. Pre-incubation of BA for 30 minutes with the superoxide scavengers tempol (1mM) or PEG-superoxide dismutase (PEG-SOD, 100 U/ml) completely restored ACh-induced relaxation to normal (ACh at 100μM: 79±7% Tempol-KO; 75±12% PEG-SOD-KO; 81±11% WT). This phenotype was very similar to that observed in HFD fed E-V290M mice. We conclude that loss of RBP7 causes endothelial dysfunction in response to a HFD through a mechanism involving oxidative stress. These findings provide the first evidence that RBP7 plays a protective role in the endothelium, which might be related to the endothelial protective effects of PPARG.

scholarly journals Context-dependent effects of SOCS3 in angiotensin II-induced vascular dysfunction and hypertension in mice: mechanisms and role of bone marrow-derived cells

2016 ◽  
Vol 311 (1) ◽  
pp. H146-H156 ◽  
Author(s):  
Ying Li ◽  
Dale A. Kinzenbaw ◽  
Mary L. Modrick ◽  
Lecia L. Pewe ◽  
Frank M. Faraci
Keyword(s):  
Bone Marrow ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Carotid Artery Disease ◽  
Vascular Dysfunction ◽  
Cytokine Signaling ◽  
Ang Ii ◽  
Direct Effects ◽  
Bone Marrow Derived Cells

Carotid artery disease is a major contributor to stroke and cognitive deficits. Angiotensin II (Ang II) promotes vascular dysfunction and disease through mechanisms that include the IL-6/STAT3 pathway. Here, we investigated the importance of suppressor of cytokine signaling 3 (SOCS3) in models of Ang II-induced vascular dysfunction. We examined direct effects of Ang II on carotid arteries from SOCS3-deficient (SOCS3+/−) mice and wild-type (WT) littermates using organ culture and then tested endothelial function with acetylcholine (ACh). A low concentration of Ang II (1 nmol/l) did not affect ACh-induced vasodilation in WT but reduced that of SOCS3+/−mice by ∼50% ( P < 0.05). In relation to mechanisms, effects of Ang II in SOCS3+/−mice were prevented by inhibitors of STAT3, IL-6, NF-κB, or superoxide. Systemic Ang II (1.4 mg/kg per day for 14 days) also reduced vasodilation to ACh in WT. Surprisingly, SOCS3 deficiency prevented most of the endothelial dysfunction. To examine potential underlying mechanisms, we performed bone marrow transplantation. WT mice reconstituted with SOCS3+/−bone marrow were protected from Ang II-induced endothelial dysfunction, whereas reconstitution of SOCS3+/−mice with WT bone marrow exacerbated Ang II-induced effects. The SOCS3 genotype of bone marrow-derived cells did not influence direct effects of Ang II on vascular function. These data provide new mechanistic insight into the influence of SOCS3 on the vasculature, including divergent effects depending on the source of Ang II. Bone marrow-derived cells deficient in SOCS3 protect against systemic Ang II-induced vascular dysfunction.

scholarly journals Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

2021 ◽  
Vol 18 (5) ◽  
pp. 2366
Author(s):  
Joshua Bond ◽  
Tessa Nielsen ◽  
Lynette Hodges
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Vascular Function ◽  
Augmentation Index ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Control Group ◽  
Fatigue Syndrome ◽  
The Impact

Background: Evidence is emerging that individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may suffer from chronic vascular dysfunction as a result of illness-related oxidative stress and vascular inflammation. The study aimed to examine the impact of maximal-intensity aerobic exercise on vascular function 48 and 72 h into recovery. Methods: ME/CFS (n = 11) with gender and age-matched controls (n = 11) were randomly assigned to either a 48 h or 72 h protocol. Each participant had measures of brachial blood pressure, augmentation index (AIx75, standardized to 75 bpm) and carotid-radial pulse wave velocity (crPWV) taken. This was followed by a maximal incremental cycle exercise test. Resting measures were repeated 48 or 72 h later (depending on group allocation). Results: No significant differences were found when ME/CFS were directly compared to controls at baseline. During recovery, the 48 h control group experienced a significant 7.2% reduction in AIx75 from baseline measures (p < 0.05), while the matched ME/CFS experienced no change in AIx75. The 72 h ME/CFS group experienced a non-significant increase of 1.4% from baseline measures. The 48 h and 72 h ME/CFS groups both experienced non-significant improvements in crPWV (0.56 ms−1 and 1.55 ms−1, respectively). Conclusions: The findings suggest that those with ME/CFS may not experience exercise-induced vasodilation due to chronic vascular damage, which may be a contributor to the onset of post-exertional malaise (PEM).

scholarly journals Vascular Alterations Among Young Adults with SARS-CoV-2

2020 ◽  
Author(s):  
Stephen M. Ratchford ◽  
Jonathon Lee Stickford ◽  
Valesha M Province ◽  
Nina Stute ◽  
Marc Andrew Augenreich ◽  
...  
Keyword(s):  
Young Adults ◽  
Arterial Stiffness ◽  
Systemic Inflammation ◽  
Vascular Function ◽  
Disease Risk ◽  
Vascular Dysfunction ◽  
Cardiovascular Disease Risk ◽  
Area Under The Curve ◽  
Control Group ◽  
Cross Sectional

Background: While SARS-CoV-2 primarily affects the lungs, the virus may be inflicting detriments to the cardiovascular system, both directly through angiotensin converting enzyme 2 receptor as well as initiating systemic inflammation. Persistent systemic inflammation may be provoking vascular dysfunction, an early indication of cardiovascular disease risk. Methods: In order to establish the potential effects of SARS-CoV-2 on the systemic vasculature in the arms and legs, we performed a cross-sectional analysis of young healthy adults (Control: 5M/15F, 23.0±1.3y, 167±9cm, 63.0±7.4kg) and young adults who, 3-4 weeks prior to testing, had tested positive for SARS-CoV-2 (SARS-CoV-2: 4M/7F, 20.2±1.1y, 172±12cm, 69.5±12.4kg) (mean±SD). Using Doppler ultrasound, brachial artery flow-mediated dilation (FMD) in the arm and single passive limb movement (sPLM) in the leg were assessed as markers of vascular function. Pulse wave velocity (PWVcf) was assessed as a marker of arterial stiffness. Results: FMD was lower in the SARS-CoV-2 group (2.71±1.21%) compared to the Control group (8.81±2.96%) (P<0.01) and when made relative to the shear stimulus (SARS-CoV-2: 0.04±0.02AU, Control: 0.13±0.06AU, P<0.01). The femoral artery blood flow response, as evidenced by the area under the curve, from the sPLM was lower in the SARS-CoV-2 group (-3±91ml) compared with the Control group (118±114ml) (P<0.01). PWVcf was higher in the SARS-CoV-2 group (5.83±0.62m/s) compared with the Control group (5.17±0.66m/s) (P<0.01). Conclusions: Significantly lower systemic vascular function and higher arterial stiffness are evident weeks after testing positive for SARS-CoV-2 among young adults compared to controls.

scholarly journals Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

2018 ◽  
Vol 314 (5) ◽  
pp. E468-E477 ◽  
Author(s):  
Micah L. Battson ◽  
Dustin M. Lee ◽  
Dillon K. Jarrell ◽  
Shuofei Hou ◽  
Kayl E. Ecton ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Arterial Stiffness ◽  
Gut Microbiota ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Nuclear Factor Κb ◽  
Western Diet ◽  
Standard Diet ◽  
Vascular Abnormalities ◽  
Gut Dysbiosis

Vascular dysfunction represents a critical preclinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesity-related vascular dysfunction. Male C57BL/6J mice were fed either a standard diet (SD) ( n = 12) or Western diet (WD) ( n = 24) for 5 mo, after which time WD mice were randomized to receive either unsupplemented drinking water or water containing a broad-spectrum antibiotic cocktail (WD + Abx) ( n = 12/group) for 2 mo. Seven months of WD caused gut dysbiosis, increased arterial stiffness (SD 412.0 ± 6.0 vs. WD 458.3 ± 9.0 cm/s, P < 0.05) and endothelial dysfunction (28% decrease in max dilation, P < 0.05), and reduced l-NAME-inhibited dilation. Vascular dysfunction was accompanied by significant increases in circulating LPS-binding protein (LBP) (SD 5.26 ± 0.23 vs. WD 11 ± 0.86 µg/ml, P < 0.05) and interleukin-6 (IL-6) (SD 3.27 ± 0.25 vs. WD 7.09 ± 1.07 pg/ml, P < 0.05); aortic expression of phosphorylated nuclear factor-κB (p-NF-κB) ( P < 0.05); and perivascular adipose expression of NADPH oxidase subunit p67phox ( P < 0.05). Impairments in vascular function correlated with reductions in Bifidobacterium spp. Antibiotic treatment successfully abrogated the gut microbiota and reversed WD-induced arterial stiffness and endothelial dysfunction. These improvements were accompanied by significant reductions in LBP, IL-6, p-NF-κB, and advanced glycation end products (AGEs), and were independent from changes in body weight and glucose tolerance. These results indicate that gut dysbiosis contributes to the development of WD-induced vascular dysfunction, and identify the gut microbiota as a novel therapeutic target for obesity-related vascular abnormalities.

Acute supplementation with beetroot juice improves endothelial function in HIV-infected individuals.

2020 ◽  
Author(s):  
Rogerio Nogueira Soares ◽  
Ana Paula Machado-Santos ◽  
Elisa Barros-Santos ◽  
Gustavo Vieira Oliveira ◽  
Juan M Murias ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Human Immunodeficiency Virus ◽  
Endothelial Function ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Control Group ◽  
Beetroot Juice ◽  
Immunodeficiency Virus ◽  
No Bioavailability ◽  
Clinical Trials Registry

Human immunodeficiency virus (HIV) is associated with lower nitric oxide (NO) bioavailability and vascular dysfunction. Nitrate-rich beetroot juice (BJ) has been shown to acutely increase NO availability and vascular function in healthy and individuals at high risk for CVD . Thus, we tested the effects of BJ ingestion on flow-mediated dilation (FMD) and pulse wave velocity (PWV) measurements in healthy and HIV-infected patients. 13 HIV-infected (36±10 years old) and 18 healthy (27±8 years old) participated in the study. Individuals were submitted to vascular tests such as FMD and pulse PWV at pre (T0) and at 120 min (T120) after beetroot juice (BJ) and placebo (PLA) ingestion. The %FMD at T0 of the control group was significantly higher than the %FMD at T0 of the HIV individuals in both interventions. BJ improved the %FMD at T120 when compared to T0 in the HIV and control groups. There was no change in %FMD after PLA ingestion in the control and HIV groups. There were no differences between groups (control vs HIV), time points (T0 vs T120) and interventions (BJ vs PLA) for PWV. Our findings showed that nitrate-rich beetroot juice ingestion acutely improved vascular function in healthy and HIV-infected patients. Clinical Trials Registry number: NCT03485248. Novelty bullets: ●Human immunodeficiency virus (HIV) is associated with lower nitric oxide (NO) bioavailability and vascular dysfunction. ●Acute supplementation with nitrate-rich beetroot juice (BJ) has been shown to acutely increases NO bioavailability ●We showed for the first time that BJ acutely improve endothelial function in HIV-infected patients.

High soluble endoglin levels accompanied by mild hypercholesterolemia are a risk factor for the development of endothelial dysfunction in mice

2018 ◽  
Vol 275 ◽  
pp. e124
Author(s):  
B. Vitverova ◽  
K. Blazickova ◽  
I. Najmanova ◽  
M. Vicen ◽  
M. Pericacho ◽  
...  
Keyword(s):  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Soluble Endoglin

Endothelial dysfunction in Type 2 diabetes correlates with deregulated expression of the tail-anchored membrane protein SLMAP

2005 ◽  
Vol 289 (1) ◽  
pp. H206-H211 ◽  
Author(s):  
Hong Ding ◽  
Andrew G. Howarth ◽  
Malarvannan Pannirselvam ◽  
Todd J. Anderson ◽  
David L. Severson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Microvascular Disease ◽  
Mesenteric Arteries ◽  
Mrna Levels ◽  
Important Indicator ◽  
Membrane Function

The Type 2 diabetic db/ db mouse experiences vascular dysfunction typified by changes in the contraction and relaxation profiles of small mesenteric arteries (SMAs). Contractions of SMAs from the db/ db mouse to the α1-adrenoceptor agonist phenylephrine (PE) were significantly enhanced, and acetylcholine (ACh)-induced relaxations were significantly depressed. Drug treatment of db/ db mice with a nonthiazolidinedione peroxisome prolifetor-activated receptor-γ agonist and insulin sensitizing agent 2-[2-(4-phenoxy-2-propylphenoxy)ethyl]indole-5-acetic acid (COOH) completely prevented the changes in endothelium-dependent relaxation, but, with the discontinuation of therapy, endothelial dysfunction returned. Dysfunctional SMAs were found to specifically upregulate the expression of a 35-kDa isoform of sarcolemmal membrane-associated protein (SLMAP), which is a component of the excitation-contraction coupling apparatus and implicated in the regulation of membrane function in muscle cells. Real-time PCR revealed high SLMAP mRNA levels in the db/ db microvasculature, which were markedly downregulated during COOH treatment but elevated again when drug therapy was discontinued. These data reveal that the microvasculature in db/ db mice undergoes significant changes in vascular function with the endothelial component of vascular dysfunction specifically correlating with the overexpression of SLMAP. Thus changes in SLMAP expression may be an important indicator for microvascular disease associated with Type 2 diabetes.

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