A Comprehensive Review of the Manifestation of Cardiovascular Diseases in HIV Patients

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

The increasing lifespan of people living with HIV (PLWH) due to advancements in antiretroviral therapy (ART) has shifted mortality patterns from AIDS-related non-AIDS-related causes, notably cardiovascular diseases (CVDs). This review investigates how and ART contribute vascular endothelial dysfunction, myocardial fibrosis, hypercoagulation, which significantly exacerbate risk. Mechanistic insights include chronic inflammation immune dysregulation persistent infection ART-specific effects such as protease inhibitors causing dyslipidemia zidovudine inducing mitochondrial toxicity leading cardiomyopathy. ART, while lifesaving, been implicated promoting subclinical atherosclerosis the risk acute infarction, further highlighting need for tailored approaches. manuscript addresses pressing obstacles, including disparities healthcare access lack standardized screening guidelines specific PLWH. It emphasizes integration advanced imaging techniques emerging biomarkers, coronary artery calcium scoring soluble ST2, detect early abnormalities. also identifies challenges selection balance virologic control safety. What sets this apart is its holistic detailed approach intersection health. not only elucidates complex pathophysiological mechanisms but offers actionable into current clinical fall short. underscores urgency implementing proactive protocols PLWH refining regimens mitigate CVD risks. By addressing these gaps, work aims expand our understanding HIV-related manifestations provide a foundation targeted interventions, thereby improving long-term health outcomes comprehensive perspective poised transform practice by fostering greater awareness among physicians encouraging development more effective strategies managing risks population.

Language: Английский

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The Interplay Between Immunity, Inflammation and Endothelial Dysfunction

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1708 - 1708

Published: Feb. 17, 2025

The endothelium is pivotal in multiple physiological processes, such as maintaining vascular homeostasis, metabolism, platelet function, and oxidative stress. Emerging evidence the past decade highlighted immunomodulatory function of endothelium, serving a link between innate, adaptive immunity inflammation. This review examines regulation immune-inflammatory axis by discusses immune functions, explores pathophysiological processes leading to endothelial dysfunction various metabolic disturbances, including hyperglycemia, obesity, hypertension, dyslipidaemia. final section focuses on novel, repurposed, emerging therapeutic targets that address dysfunction.

Language: Английский

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Suppression of NLRP3 inflammasome by a small molecule targeting CK1α–β-catenin–NF-κB and CK1α–NRF2–mitochondrial OXPHOS pathways during mycobacterial infection

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Introduction Pyroptosis is an important inflammatory form of cell death and Mycobacterium tuberculosis ( M.tb ) chronic infection triggers excessive pyroptosis macrophages. Our previous research has confirmed that a small compound pyrvinium pamoate (PP) could inhibit pathological changes mycobacterial burden in -infected mice, but the potential mechanism PP for inhibiting -induced inflammation remains unexplored. Methods The effects on NLRP3-ASC-Casp1 inflammasome assembly activation, gasdermin D (GSDMD) mediated cytokines expression were assessed human THP-1-derived macrophages after H37Rv/H37Ra/ Salmonella typhimurium S. or LPS treatment by Transcriptome sequencing, RT-qPCR, Co-immunoprecipitation Western Blot (WB) analysis. lactate dehydrogenase (LDH) release assay was used to evaluate CC50 THP-1 cells. Results We found / significantly activate GSDMD-mediated (IL-1β IL-18) macrophages, whereas suppress these dose dependent manner. Regarding PP-inhibition mechanism, we further this inhibitory activity through PP-targeting casein kinase 1A1 (CK1α)–β-catenin–NF-κB pathway CK1α–NRF2–mitochondrial oxidative phosphorylation (OXPHOS) pathway. In addition, CK1α specific inhibitor D4476 siRNA reverse bacteria-induced responses Conclusions This study reveals previously unreported can NLRP3 GSDMD–IL-1β via targeting suppressing CK1α–β-catenin–NF-κB OXPHOS pathways, suggesting holds great promise as host directed therapy (HDT) drug mycobacterial-induced response.

Language: Английский

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Immuno-cell metabolic changes in HIV-1 infection

Infectious Diseases & Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Recent research has shown that metabolic processes within immune cells are essential for both human immunodeficiency virus 1 (HIV-1) infection and the response. Throughout HIV-1 infection—from acute stages to chronic viral latency—immune experience shifts in energy demands pathways, paralleling T-cell exhaustion. Dysregulated metabolism compromises cell function, leading dysfunction persistent inflammation. Therefore, alterations constitute a critical mechanism progression This review specifically explores profiles roles of T cells, monocytes-macrophages, dendritic natural killer B at different infection, emphasizing effects on pathways diverse types. These insights offer valuable therapeutic strategies aimed inhibiting replication, restoring controlling disease progression.

Language: Английский

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Virtual adaptation of a nurse-driven strategy to improve blood pressure control among people with HIV

HIV Research & Clinical Practice, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 18, 2025

People with HIV are at increased risk of cardiovascular events; thus, care delivery strategies that increase access to comprehensive disease (CVD) management a priority. We report the results multi-component telemedicine-based strategy improve blood pressure control among people HIV—Assess and Adapt Impact COVID-19 on CVD Self-Management Prevention Care in Adults Living (AAIM-High). The AAIM High is virtual adaptation our previously published EXTRA-CVD consisted hypertension education six components: nurse-led coordination (delivered by teleconference or telephone), home systolic (SBP) monitoring, evidence-based treatment algorithms, electronic health records tools, technology coach, communication preferences assessment. (n = 74) comorbid three academic medical centers were enrolled single arm implementation study from January 2021 December 2022. Over 12 months, average patient-performed SBP decreased 7.7 mmHg (95% CI −11.5, −3.9). percentage patients goal, defined as <130 mmHg, 46.0% 72.5% months. By adapting growing use telemedicine healthcare delivery, effectively improved through virtual, intervention.

Language: Английский

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Clonal hematopoiesis of indeterminate potential: contribution to disease and promising interventions

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

In clonal hematopoiesis of indeterminate potential (CHIP), subpopulations blood cells carrying somatic mutations expand as the individual ages, and this expansion may elevate risk cancers well cardiovascular disease. Individuals at higher CHIP therefore CHIP-associated disease can be identified through mutational profiling, apparently central role inflammation in has emerged a therapeutic target. While is often associated with negative health outcomes, emerging evidence suggests that some CHIP-related also exert beneficial effects, indicating more complex human health. This review examines current understanding epidemiology clinical significance driving its association risk. It explores mechanisms linking to other diseases, personalizing therapies against those diseases for individuals CHIP.

Language: Английский

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Elevated Methylglyoxal: An Elusive Risk Factor Responsible for Early-Onset Cardiovascular Diseases in People Living with HIV-1 Infection

Viruses, Journal Year: 2025, Volume and Issue: 17(4), P. 547 - 547

Published: April 8, 2025

People living with HIV (PLWH) develop cardiovascular diseases (CVDs) about a decade earlier and at rates 2–3 times higher than the general population. At present, pharmacological strategies to delay onset of CVDs in PLWH are unavailable, part because an incomplete understanding its molecular causes. We others recently uncovered elevated levels toxic glycolysis inflammation-induced byproduct methylglyoxal (MG) plasma from HIV-infected humanized mice (Hu-mice). also found reduction expression primary MG-degrading enzyme glyoxalase I (Glo-I) autopsied cardiac tissues HIV-1-infected individuals Hu-mice. Increasing Glo-I Hu-mice not only attenuated heart failure but reduced endothelial cell damage, increased density perfused microvessels, prevented microvascular leakage micro-ischemia, blunted protein vascular protein-1 (VAP-1), key mediators CVDs. In this narrative review, we posit that MG is contributing cause for early PLWH. Pharmacological prevent accumulation development early-onset discussed.

Language: Английский

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Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation

Antioxidants, Journal Year: 2024, Volume and Issue: 14(1), P. 38 - 38

Published: Dec. 31, 2024

Oxidative stress plays a pivotal role in the pathogenesis and progression of cardiovascular diseases (CVDs). This review focuses on signaling pathways oxidative during development CVDs, delving into molecular regulatory networks underlying various disease stages, particularly apoptosis, inflammation, fibrosis, metabolic imbalance. By examining dual roles influences sex differences levels susceptibility, this study offers comprehensive understanding diseases. The integrates key findings from current research three ways. First, it outlines major CVDs associated with their respective pathways, emphasizing stress’s central pathology. Second, summarizes protective effects, mechanisms action, animal models antioxidants, offering insights future drug development. Third, discusses applications, advantages, limitations, potential targets gene therapy providing foundation for novel therapeutic strategies. These tables underscore systematic integrative nature while theoretical basis precision treatment CVDs. A contribution is differential effects across different stages addition to proposal innovative, multi-level intervention strategies, which open new avenues system.

Language: Английский

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The Primacy of Adipose Tissue Gene Expression and Plasma Lipidome in Cardiometabolic Disease in Persons With HIV

The Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: 231(2), P. e407 - e418

Published: Dec. 4, 2024

Persons with HIV (PWH) on contemporary antiretroviral therapy (ART) are at elevated risk for developing age-related cardiometabolic diseases. We hypothesized that integrative analysis of cross-tissue, multimodal data from PWH could provide insight into molecular programming defines phenotypes in this high-risk group. enrolled 93 without diabetes who were virologically suppressed ART and obtained measures insulin resistance, glucose intolerance, adiposity. performed circulating lipidomics, proteomics, metabolomics, as well subcutaneous adipose tissue (SAT) bulk transcriptomics, used multiomics factor (MOFA) to perform analyses these datasets. The median age was 43 years, body mass index 30.8 kg/m2, 81% male, 56% self-identified non-Hispanic White. identified a specific MOFA associated visceral volume (ρ = -0.43), homeostasis model assessment 2 resistance score -0.52), liver density 0.43), other factors, which explained more variance the SAT transcriptome lipidome compared proteome metabolome. Gene set enrichment showed extracellular matrix inflammatory pathways primarily mapped myeloid cells progenitor using single-cell deconvolution. Lipidomic significantly enriched triacylglycerol diacylglycerol species. Our multiomic demonstrated coordinated, multitissue reprogramming disease risk. Longitudinal studies assessments lipid handling necessary understand mechanisms PWH. Clinical Trials Registration. NCT04451980.

Language: Английский

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Metformin in Antiviral Therapy: Evidence and Perspectives

Viruses, Journal Year: 2024, Volume and Issue: 16(12), P. 1938 - 1938

Published: Dec. 18, 2024

Metformin, a widely used antidiabetic medication, has emerged as promising broad-spectrum antiviral agent due to its ability modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes energy reserves that viruses rely on, effectively limiting the replication of pathogens such influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting mTOR pathway, crucial protein synthesis reactivation, is particularly significant managing infections caused by CMV, EBV. Furthermore, reduces oxidative stress reactive oxygen species (ROS), which are critical replicating arboviruses Zika dengue. The drug also regulates immune responses, differentiation, inflammation, disrupting life cycle HPV potentially other viruses. These diverse mechanisms suppress replication, enhance system functionality, contribute better clinical outcomes. This multifaceted approach highlights metformin’s potential an adjunctive therapy treating wide range infections.

Language: Английский

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