scholarly journals Effect of HIV‐1 Infection on Angiopoietin 1 and 2 Levels and Measures of Microvascular and Macrovascular Endothelial Dysfunction

2021 ◽  
Author(s):  
Anjali B. Thakkar ◽  
Yifei Ma ◽  
Mark Dela Cruz ◽  
Yuaner Wu ◽  
Victor Arechiga ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Hiv Infection ◽  
Brachial Artery ◽  
Microvascular Dysfunction ◽  
Receptor System ◽  
Vascular Homeostasis ◽  
Untreated Individuals ◽  
The Impact ◽  
Angiopoietin 1

Background Individuals infected with HIV have an increased risk of developing cardiovascular disease; yet, the underlying mechanisms remain unknown. Recent evidence has implicated the Tie‐2 tyrosine kinase receptor system and its associated ligands ANG1 (angiopoietin 1) and ANG2 (angiopoietin 2) in maintaining vascular homeostasis. In the general population, lower ANG1 levels and higher ANG2 levels are strongly correlated with the development of cardiovascular disease. In this study, we aim to investigate the associations of HIV infection with angiopoietin levels and endothelial dysfunction. Methods and Results In this cross‐sectional study, we compared measures of ANG1, ANG2, and endothelial dysfunction using flow‐mediated vasodilation of the brachial artery in 39 untreated subjects infected with HIV, 47 treated subjects infected with HIV, and 46 uninfected subjects from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort. Compared with uninfected controls, treated individuals infected with HIV had 53.1% lower mean ANG1 levels ( P <0.01) and similar ANG2 levels. On the other hand, untreated individuals infected with HIV had similar ANG1 levels, and 29.2% had higher ANG2 levels ( P <0.01) compared with uninfected controls. When compared with individuals with untreated HIV infection, those with treated HIV infection had 56% lower ANG1 levels ( P <0.01) and 22% lower ANG2 levels ( P <0.01).Both treated and untreated HIV infection were associated with significant impairment in hyperemic velocity, a key measure of microvascular dysfunction (median 61 versus 72 cm/s, P <0.01), compared with uninfected controls (median 73 cm/s). This difference persisted after adjustment for ANG1 and ANG2 levels. Interestingly, when compared with untreated individuals infected with HIV, treated individuals infected with HIV had worse hyperemic velocity (−12.35 cm/s, P =0.05). In contrast, HIV status, ANG1 levels, and ANG2 levels were not associated with macrovascular dysfunction as measured by flow‐mediated dilatation and brachial artery diameter, 2 other measures of vascular homeostasis. Conclusions HIV infection affects the balance between levels of ANG1 and ANG2 and may disturb endothelial homeostasis through disruption of vascular homeostasis. Individuals with treated HIV had decreased ANG1 levels and similar ANG2 levels, whereas individuals with untreated HIV had similar ANG1 levels and increased ANG2 levels, suggesting that treatment status may alter the balance between ANG1 and ANG2. HIV also promotes endothelial dysfunction via impairment of microvascular dysfunction, independent of the Tie‐2 receptor system; the finding of worse microvascular dysfunction in the setting of treated HIV infection may reflect the impact of viral persistence on the microvasculature or toxicities of specific antiretroviral regimens. Further research to clarify the mechanism of HIV‐mediated endothelial dysfunction is necessary to advance treatment of cardiovascular complications of HIV infection.

Abstract 368: Family History of Premature Cardiac Events and Sub Clinical Atherosclerosis in Children and Young Adults: A Systematic Review

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Pragya Sinha ◽  
Jamal S Rana ◽  
Ebenezer T Oni ◽  
Ehimen C Aneni ◽  
Roger S Blumenthal ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Young Adults ◽  
Family History ◽  
Endothelial Dysfunction ◽  
Subclinical Atherosclerosis ◽  
Vascular Inflammation ◽  
Positive Family History ◽  
Cardiac Risk Factor ◽  
Children And Young Adults ◽  
The Impact

BACKGROUND The association between a positive family history (PFH) of premature cardiovascular disease (PCVD) and atherosclerosis has been explored in numerous studies. In adults, various studies have confirmed a significant positive correlation between a PFH and PCVD. Scant literature however, focuses on young individuals. Nevertheless, it is important to understand the impact that a PFH has in young people because the foundations of atherosclerosis and adverse cardiac behaviors develop in youth. In this paper, we aimed to systematically review the evidence linking a PFH of PCVD to indirect markers of subclinical atherosclerosis. METHODS The search was conducted on Medline, Web of Science and Embase. ‘Family history’, ‘children/young adults’ and ‘subclinical atherosclerosis’ were the three main concepts used. Increase in mean carotid IMT (cIMT), endothelial dysfunction and vascular inflammation were used as indirect measures of subclinical atherosclerosis. RESULTS 1191 articles were identified in the initial search. 24 papers with 5400 participants were included in the final review. There were five cohort studies and nineteen case control studies from twelve countries. Mean cIMT was found to be significantly increased in those with a PFH by eleven of the fourteen papers reviewed. Endothelial dysfunction, measured by flow mediated dilatation (FMD), was found to be significantly increased in five of the seven included studies. The evidence on vascular inflammation was somewhat inconsistent with only ten of the nineteen studies demonstrating significance. The results tend to suggest that an elevated mean cIMT, as well as a greater degree of endothelial dysfunction are seen in children and young adults with a PFH of PCVD. Moreover, these differences exist in asymptomatic children as young as 8-9 years (4 studies) in the absence of any other cardiac risk factor. DISCUSSION Individuals with a PFH of PCVD have evidence of subclinical atherosclerosis in their youth demonstrating an accelerated tendency to acquire cardiovascular disease. Some of this risk may be attributable to behavioral risk clustering in families. However, a significant proportion of this elevated risk is related solely to a positive family history and needs attention.

scholarly journals Endothelial Dysfunction and Cardiovascular Disease: History and Analysis of the Clinical Utility of the Relationship

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 699
Author(s):  
Peter J. Little ◽  
Christopher D. Askew ◽  
Suowen Xu ◽  
Danielle Kamato
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Cell Monolayer ◽  
Modern Times ◽  
Protein Receptor ◽  
Endocrine Secretion ◽  
The Impact ◽  
The Relationship ◽  
Vascular Senescence

The endothelium is the single-cell monolayer that lines the entire vasculature. The endothelium has a barrier function to separate blood from organs and tissues but also has an increasingly appreciated role in anti-coagulation, vascular senescence, endocrine secretion, suppression of inflammation and beyond. In modern times, endothelial cells have been identified as the source of major endocrine and vaso-regulatory factors principally the dissolved lipophilic vosodilating gas, nitric oxide and the potent vascular constricting G protein receptor agonists, the peptide endothelin. The role of the endothelium can be conveniently conceptualized. Continued investigations of the mechanism of endothelial dysfunction will lead to novel therapies for cardiovascular disease. In this review, we discuss the impact of endothelial dysfunction on cardiovascular disease and assess the clinical relevance of endothelial dysfunction.

scholarly journals Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Rusan Catar ◽  
Guido Moll ◽  
Julian Kamhieh-Milz ◽  
Christian Luecht ◽  
Lei Chen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
End Stage Renal Disease ◽  
Cytokine Signaling ◽  
Dialysis Patients ◽  
Vegf Expression ◽  
Tnf Α ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Impact

AbstractSystemic chronic microinflammation and altered cytokine signaling, with adjunct cardiovascular disease (CVD), endothelial maladaptation and dysfunction is common in dialysis patients suffering from end-stage renal disease and associated with increased morbidity and mortality. New hemodialysis filters might offer improvements. We here studied the impact of novel improved molecular cut-off hemodialysis filters on systemic microinflammation, uremia and endothelial dysfunction. Human endothelial cells (ECs) were incubated with uremic serum obtained from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation (PERCI-II) crossover clinical trial, comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes, and then assessed for their vascular endothelial growth factor (VEGF) production and angiogenesis. Compared to HF membranes, dialysis with MCO membranes lead to a reduction in proinflammatory mediators and reduced endothelial VEGF production and angiogenesis. Cytokine multiplex screening identified tumor necrosis factor (TNF) superfamily members as promising targets. The influence of TNF-α and its soluble receptors (sTNF-R1 and sTNF-R2) on endothelial VEGF promoter activation, protein release, and the involved signaling pathways was analyzed, revealing that this detrimental signaling was indeed induced by TNF-α and mediated by AP-1/c-FOS signaling. In conclusion, uremic toxins, in particular TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel MCO membranes.Translational Perspective and Graphical AbstractSystemic microinflammation, altered cytokine signaling, cardiovascular disease, and endothelial maladaptation/dysfunction are common clinical complications in dialysis patients suffering from end-stage renal disease. We studied the impact of novel improved medium-cut-off hemodialysis filters on uremia and endothelial dysfunction. We can show that uremic toxins, especially TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel improved medium-cut-off membranes.

scholarly journals Imbalance between Endothelial Damage and Repair: A Gateway to Cardiovascular Disease in Systemic Lupus Erythematosus

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Anselm Mak ◽  
Nien Yee Kow
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Lupus Erythematosus ◽  
Cardiovascular Complications ◽  
Endothelial Damage ◽  
Clinical Diagnostics ◽  
Vascular Repair ◽  
Systemic Lupus ◽  
The Impact

Atherosclerosis is accelerated in patients with systemic lupus erythematosus (SLE) and it leads to excessive cardiovascular complications in these patients. Despite the improved awareness of cardiovascular disease and advent of clinical diagnostics, the process of atherogenesis in most patients remains clinically silent until symptoms and signs of cardiovascular complications develop. As evidence has demonstrated that vascular damage is already occurring before clinically overt cardiovascular disease develops in lupus patients, intervention at the preclinical stage of atherogenesis would be plausible. Indeed, endothelial dysfunction, one of the earliest steps of atherogenesis, has been demonstrated to occur in lupus patients even when they are naïve for cardiovascular disease. Currently known “endothelium-toxic” factors including type 1 interferon, proinflammatory cytokines, inflammatory cells, immune complexes, costimulatory molecules, neutrophils extracellular traps, lupus-related autoantibodies, oxidative stress, and dyslipidemia, coupled with the aberrant functions of the endothelial progenitor cells (EPC) which are crucial to vascular repair, likely tip the balance towards endothelial dysfunction and propensity to develop cardiovascular disease in lupus patients. In this review, altered physiology of the endothelium, factors leading to perturbed vascular repair contributed by lupus EPC and the impact of proatherogenic factors on the endothelium which potentially lead to atherosclerosis in lupus patients will be discussed.

Aging attenuates the protective effect of ischemic preconditioning against endothelial ischemia-reperfusion injury in humans

2013 ◽  
Vol 304 (12) ◽  
pp. H1727-H1732 ◽  
Author(s):  
Inge van den Munckhof ◽  
Niels Riksen ◽  
Joost P. H. Seeger ◽  
Tim H. Schreuder ◽  
George F. Borm ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Ischemic Preconditioning ◽  
Brachial Artery ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
The Elderly ◽  
Upper Arm ◽  
Before And After ◽  
The Impact

Reperfusion is mandatory after ischemia but also triggers ischemia-reperfusion (I/R) injury. Ischemic preconditioning (IPC) can limit endothelial I/R injury. Nonetheless, translation of IPC to the clinical arena is often disappointing. Since application of IPC typically relates to older patients, efficacy of IPC may be attenuated with aging. Our objective was to examine the impact of advanced age on the ability of IPC to protect against endothelial dysfunction due to I/R injury. We included 15 healthy young (20–25 yr) and 15 older (68–77 yr) men. We examined brachial artery endothelial function using flow-mediated dilation (FMD) before and after arm I/R (induced by inflation of an upper-arm blood pressure cuff for 20 min and 15 min of reperfusion). In a randomized order, I/R was preceded by IPC or a control intervention consisting of three cycles of 5 min upper-arm cuff inflation to 220 or 20 mmHg, respectively. As a result, in young men, FMD decreased significantly after I/R (6.4 ± 2.7 to 4.4 ± 2.5%). This decrease was not present when I/R was preceded by IPC (5.9 ± 2.3 to 5.6 ± 2.5%). IPC-induced protection appeared to be significantly reduced in the elderly patients ( P = 0.04). Although FMD decreased after I/R in older men (3.5 ± 1.7 to 2.5 ± 1.0%), IPC could not prevent this (3.7 ± 2.1 to 2.2 ± 1.1%). In conclusion, this study is the first to observe in humans in vivo that older age is associated with an abolished effect of IPC to protect against endothelial dysfunction after I/R in the brachial artery. This provides a possible explanation for the problematic translation of strategies that reduce I/R injury from preclinical work to the clinical arena.

Abstract 078: Total Brachial Artery Reactivity And Incident Heart Failure And Heart Failure Sub-types: Multi-ethnic Study Of Atherosclerosis

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Daniela Charry
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Ejection Fraction ◽  
Brachial Artery ◽  
Minimum Diameter ◽  
Ethnic Study ◽  
Increased Risk ◽  
The Impact ◽  
Brachial Artery Reactivity

Introduction: Endothelial dysfunction may be a phenotypic expression of heart failure (HF). Total brachial artery reactivity (TBAR) is a non-invasive measurement of endothelial function that has been associated with increased risk of cardiovascular outcomes. Limited information is currently available on the impact of TBAR on incident HF and its subtypes. The aim of this study was to evaluate whether TBAR is associated with incident HF, HF with reduced ejection fraction (HFrEF), or HF with preserved ejection fraction (HFpEF) in a community-based study. Hypothesis: We hypothesized that TBAR would be inversely related with incident HF and both HF subtypes. Methods: Sample included 5,499 participants (45-84 years of age) from the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at baseline. Brachial artery ultrasound was performed after five minutes of cuff occlusion at the right forearm. TBAR was calculated as the difference between maximum and minimum brachial artery diameters following cuff release, divided by the minimum diameter multiplied by 100%. A dichotomous TBAR variable was created based on the median value (below or above 7.9%). Participants with EF ≤ 40% were considered HFrEF and those with EF ≥ 50% were considered HFpEF. Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals. Results: Over a mean follow-up period of 12.5 years, incident HF was diagnosed in 250 participants; 106 classified as HFpEF, 98 as HFrEF, and 46 with unknown or borderline EF (41-49%). Crude analysis revealed that those with TBAR below the median have significantly higher risk of HF (HR 1.46; 95% CI 1.13-1.88, p<0.01) and HFrEF (HR 1.61; 95% CI 1.07-2.43, p<0.05). Following adjustment for known HF risk factors (e.g. age, gender, race, blood pressure, others), these relationships were no longer statistically significant. Borderline significant results were revealed in those with HFpEF (HR 1.43; 95% CI 0.97-2.12, p=0.06). Kaplan-Meier curves suggest significantly lower risks of developing HF and HFrEF in those with TBAR above the median (log-rank p<0.05 for both). When examined as a continuous variable, with a cut point of 50% for EF, every 1-standard deviation (9.7%) increase in TBAR resulted in a 19% and 29% decrease in risk of HF (p<0.05) and HFrEF (p=0.05), respectively. Conclusions: Lower TBAR values were associated with higher rates of incident HF and HFrEF, suggesting a possible role of endothelial dysfunction in HF pathogenesis. The impact of other known HF risk factors may mediate this relationship, thus further research is warranted.

scholarly journals Effects of HIV Infection on Arterial Endothelial Function

2020 ◽  
Author(s):  
James H. Stein ◽  
Noah Kime ◽  
Claudia E. Korcarz ◽  
Heather Ribaudo ◽  
Judith S. Currier ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Function ◽  
Hiv Infection ◽  
Brachial Artery ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Covariate Adjustment ◽  
People Living With Hiv ◽  
Hiv Serostatus ◽  
Living With Hiv

Objective: To determine the effects of HIV serostatus and disease severity on endothelial function in a large pooled cohort study of people living with HIV infection and HIV− controls. Approach and Results: We used participant-level data from 9 studies: 7 included people living with HIV (2 treatment-naïve) and 4 had HIV− controls. Brachial artery flow-mediated dilation (FMD) was measured using a standardized ultrasound imaging protocol with central reading. After data harmonization, multiple linear regression was used to examine the effects of HIV− serostatus, HIV disease severity measures, and cardiovascular disease risk factors on FMD. Of 2533 participants, 986 were people living with HIV (mean 44.4 [SD 11.8] years old) and 1547 were HIV− controls (42.9 [12.2] years old). The strongest and most consistent associates of FMD were brachial artery diameter, age, sex, and body mass index. The effect of HIV+ serostatus on FMD was strongly influenced by kidney function. In the highest tertile of creatinine (1.0 mg/dL), the effect of HIV+ serostatus was strong (β=−1.59% [95% CI, −2.58% to −0.60%], P =0.002), even after covariate adjustment (β=−1.36% [95% CI, −2.46% to −0.47%], P =0.003). In the lowest tertile (0.8 mg/dL), the effect of HIV+ serostatus was strong (β=−1.90% [95% CI, −2.58% to −1.21%], P <0.001), but disappeared after covariate adjustment. HIV RNA viremia, CD4+ T-cell count, and use of antiretroviral therapy were not meaningfully associated with FMD. Conclusions: The significant effect of HIV+ serostatus on FMD suggests that people living with HIV are at increased cardiovascular disease risk, especially if they have kidney disease.

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