Hypertension and human immunodeficiency virus: A paradigm for epithelial sodium channels?

Mutengo, Katongo Hope; Masenga, Sepiso K.; Mwesigwa, Naome; Patel, Kaushik P.; Kirabo, Annet

doi:10.3389/fcvm.2022.968184

Cited by 8 publications

(6 citation statements)

References 213 publications

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“…Additionally, it has been suggested ART can synergize with other factors, such as increased glucose, reduced insulin production, and activation of the renin–angiotensin–aldosterone system (RAAS) and increase the activity of the endothelial sodium channel. This process can result in vasoconstriction, increased vascular permeability and activation of innate cells, which have also been linked to the development of hypertension [36]. Establishing how different ART regimens may impact BP changes can inform antihypertensive medication choices, such as using angiotensin‐converting enzyme inhibitors (ACEIs) or ARBs to counteract the possible ART‐induced RAAS activation.…”

Section: Discussionmentioning

confidence: 99%

Characterizing blood pressure trajectories in people living with HIV following antiretroviral therapy: A systematic review

et al. 2023

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ObjectivesThe advent of antiretroviral therapy (ART) has reduced AIDS‐related morbidity and mortality among people living with HIV (PLWH). Due to increased survival, PLWH have now been found to be at risk of chronic conditions related to ageing, such as cardiovascular disease (CVD). Hypertension is common in PLWH and is a major risk factor for the development of CVD. We conducted a systematic literature review to evaluate the research evidence on longitudinal blood pressure (BP) trajectories following ART initiation in PLWH.MethodsWe searched the following databases: PubMed, CINHAL, Scopus, and Web of Science (up to 15 March 2021) for peer‐reviewed published studies that reported BP trajectories following ART initiation in PLWH. Three reviewers independently screened all studies by title and abstract. We included articles in English, published up to March 2021, that report office BP trajectories in PLWH initiating ART. A total of 10 publications met our inclusion criteria. Eight studies were prospective cohorts and two were retrospective.ResultsNine out of 10 studies in the literature reported an increase in systolic BP (4.7–10.0 mmHg in studies with a follow‐up range of 6 months to 8 years, and 3.0–4.7 mmHg/year in time‐averaged studies). In addition, four out of 10 studies reported increases in diastolic BP (2.3–8.0 mmHg for a 6 month to 6.8‐year follow‐up range and 2.3 mmHg/year).ConclusionSystolic BP consistently increases while diastolic BP changes are more heterogeneous following ART initiation in PLWH. However, the studies were highly variable with respect to population demographics, ART regimen and duration, and follow‐up time. Nevertheless, given the risks of CVD complications, such as stroke, heart failure and myocardial infarction, associated with elevated BP, results highlight the importance of future research in this area. It will be important to better characterize BP trajectories over time, identify the most critical times for interventions to reduce BP, determine the long‐term CVD consequences in PLWH with elevated BP, and understand how different ART regimens may or may not influence BP and CVD disease.

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Section: Discussionmentioning

confidence: 99%

Characterizing blood pressure trajectories in people living with HIV following antiretroviral therapy: A systematic review

et al. 2023

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“…Of note, almost all PWH with hypertension have salt sensitivity [ 46 ]. Although the effects of HIV on ENaC are not well understood, we recently showed that SSBP is more prominent in PWH [ 72 ], and hypothesized that ENaC contributes to vascular dysfunction in this patient population [ 73 ▪ ]. Novel therapeutic targets specific for ENaC of immune cells may ameliorate vascular dysfunction in PWH.…”

Section: Targeting Epithelial Sodium Channel In Specific Patient Groupsmentioning

confidence: 99%

Dendritic cell epithelial sodium channel induced inflammation and salt-sensitive hypertension

Demirci,

Hinton,

Kirabo

2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease. Epithelial sodium channel (ENaC) plays a critical role in renal electrolyte and volume regulation and has been implicated in the pathogenesis of SSBP. This review describes recent advances regarding the role of ENaC-dependent inflammation in the development of SSBP. Recent findings We recently found that sodium enters dendritic cells via ENaC, a process regulated by serum/glucocorticoid-regulated kinase 1 and epoxyeicosatrienoic acid 14,15. Sodium entry activates NADPH oxidase, leading to the production of isolevuglandins (IsoLGs). IsoLGs adduct self-proteins to form neoantigens in dendritic cells that activate T cells and result in the release of cytokines promoting sodium retention, kidney damage, and endothelial dysfunction in SSBP. Additionally, we described a novel mechanistic pathway involving ENaC and IsoLG-dependent NLRP3 inflammasome activation. These findings hold promise for the development of novel diagnostic biomarkers and therapeutic options for SSBP. Summary The exact mechanisms underlying SSBP remain elusive. Recent advances in understanding the extrarenal role of ENaC have opened a new perspective, and further research efforts should focus on understanding the link between ENaC, inflammation, and SSBP.

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“…Thus, altered ENaC function as a mediator of hypertension in PLHIV remains a hypothesis for now, requiring additional studies. 154…”

Section: Niwaha and Byrdmentioning

confidence: 99%

Cardiovascular Dynamics in HIV: The Influence of Adrenal Function and Nutritional Status

Niwaha,

Byrd

2024

Circulation Research

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This interdisciplinary review explores the intricate nexus between HIV infection, nutrition, adrenal gland function, and cardiovascular health, highlighting a critical aspect of HIV management often overlooked in current literature. With the advent of antiretroviral therapy, the life expectancy of people living with HIV has dramatically improved, transforming HIV into a manageable chronic condition. However, this success brings forth new challenges, notably an increased risk of cardiovascular diseases among people living with HIV. We examine the normal physiology of the adrenal gland, including its role in mineral metabolism, a crucial facet of nutrition. We discuss the evolution of knowledge tying adrenal pathology to cardiovascular disease. We explore the impact of HIV on adrenal gland findings from a gross pathology perspective, as well as the clinical impact of adrenal insufficiency in HIV. The review further elucidates the role of nutrition in this context, considering the double burden of undernutrition and obesity prevalent in regions heavily affected by HIV. By aggregating findings from longitudinal studies and recent clinical trials, the review presents compelling evidence of increased cardiovascular disease among people living with HIV compared with people without HIV. It highlights the critical role of the adrenal glands in regulating nutrient metabolism and its implications for cardiovascular health, drawing attention to the potential for dietary interventions and targeted therapies to mitigate these risks. This review urges a paradigm shift in the management of HIV, advocating for a holistic approach that incorporates nutritional assessment and interventions into routine HIV care to address the complex interplay between HIV, adrenal function, and cardiovascular health. Through this lens, we offer insights into novel therapeutic strategies aimed at reducing cardiovascular risk in people living with HIV, contributing to the ongoing efforts to enhance the quality of life and longevity in this population.

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Hypertension and human immunodeficiency virus: A paradigm for epithelial sodium channels?

Cited by 8 publications

References 213 publications

Characterizing blood pressure trajectories in people living with HIV following antiretroviral therapy: A systematic review

Characterizing blood pressure trajectories in people living with HIV following antiretroviral therapy: A systematic review

Dendritic cell epithelial sodium channel induced inflammation and salt-sensitive hypertension

Cardiovascular Dynamics in HIV: The Influence of Adrenal Function and Nutritional Status

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