Impact of human immunodeficiency virus on pulmonary vascular disease

Kumar, Ashok; Mahajan, Aatish; Salazar, Ethan A.; Pruitt, Kevin; Guzman, Christian Arce; Clauss, Matthias; Almodóvar, Sharilyn; Dhillon, Navneet K.

doi:10.21542/gcsp.2021.12

Cited by 9 publications

(25 citation statements)

References 228 publications

(271 reference statements)

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“…To this end, first of all, using the PubMed database [ 69 ], we characterized each of the 42 hippocampal DEGs (of tame versus aggressive rats) identified in this work ( Table 2 ), in terms of how downregulation or upregulation of their orthologous human genes can manifest itself in hypertension, as presented [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ,…”

Section: Resultsmentioning

confidence: 99%

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

Oshchepkov

Chadaeva

Kozhemyakina

et al. 2022

IJMS

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Although half of hypertensive patients have hypertensive parents, known hypertension-related human loci identified by genome-wide analysis explain only 3% of hypertension heredity. Therefore, mainstream transcriptome profiling of hypertensive subjects addresses differentially expressed genes (DEGs) specific to gender, age, and comorbidities in accordance with predictive preventive personalized participatory medicine treating patients according to their symptoms, individual lifestyle, and genetic background. Within this mainstream paradigm, here, we determined whether, among the known hypertension-related DEGs that we could find, there is any genome-wide hypertension theranostic molecular marker applicable to everyone, everywhere, anytime. Therefore, we sequenced the hippocampal transcriptome of tame and aggressive rats, corresponding to low and high stress reactivity, an increase of which raises hypertensive risk; we identified stress-reactivity-related rat DEGs and compared them with their known homologous hypertension-related animal DEGs. This yielded significant correlations between stress reactivity-related and hypertension-related fold changes (log2 values) of these DEG homologs. We found principal components, PC1 and PC2, corresponding to a half-difference and half-sum of these log2 values. Using the DEGs of hypertensive versus normotensive patients (as the control), we verified the correlations and principal components. This analysis highlighted downregulation of β-protocadherins and hemoglobin as whole-genome hypertension theranostic molecular markers associated with a wide vascular inner diameter and low blood viscosity, respectively.

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Section: Resultsmentioning

confidence: 99%

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

Oshchepkov

Chadaeva

Kozhemyakina

et al. 2022

IJMS

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“…Once binding occurs, gp120 undergoes a conformational change, exposing coreceptors on gp120 to bind to chemokine C-X-C type 4 receptor (CXCR4) / C-C chemokine receptor 5 (CCR5) co-receptors on the host immune cells. The HIV virions which bind with CCR5 are known as R5 viruses, while those attached to CXCR4 are X4 viruses [16,18]. ECs are seemingly resistant to HIV infection [6,19] since HIV virions, HIV-DNA, p24 antigen, or HIV-RNA have not been isolated from the pulmonary ECs [7][8][9]18].…”

Section: Hiv-gp120mentioning

confidence: 99%

“…It results in the upregulation of the VEGF receptor, ensuing angiogenesis [16]. Both Tat and morphine cause overexpression of NOX enzymes that induce oxidative stress [30] on the pulmonary ECs, resulting in smooth muscle migration, proliferation, and vascular remodeling [16,20]. Likewise, Tat protein inhibits the activity of DNA-PK cs, the DNA repair protein, leading to the accumulation of damaged DNA and oxidative stress [2] Tat: transactivator of transcription; Tip60: Tat interacting protein 60KDa; ATM: ataxia telangiectasia mutated; VEGF: vascular endothelial growth factor; NOX: NADPH oxidase enzyme; ECs: endothelial cells; DNA-PKcs: DNA protein kinase catalytic subunit; P: phosphorylation; HIV: human immunodeficiency virus Image credit: Jaimee Jacob Palakeel…”

Section: Figure 3: the Effect Of Hiv-tat Protein And Morphine On The ...mentioning

confidence: 99%

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An Outlook on the Etiopathogenesis of Pulmonary Hypertension in HIV

Palakeel¹,

Ali²,

Chaduvula³

et al. 2022

Cureus

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Although overall survival rates of patients infected with human immunodeficiency virus (HIV) have been significantly improved by antiretroviral therapy (ART), chronic comorbidities associated with HIV result in a worsening quality of life. Pulmonary arterial hypertension (PAH) is the most prevalent comorbidity associated with HIV infection. Despite low viremia and a non-replicative state maintained by ART, few people develop PAH. Previous data from animal models and human pulmonary microvascular endothelial cells (HPMVECs) suggests a constellation of events occurring during the propagation of HIV-associated PAH (HIV-PAH). However, these studies have not successfully isolated HIV virions, HIV-DNA, protein 24 antigen (p24), or HIV-RNA from the pulmonary endothelial cells (ECs). It provides an insight into an ongoing inflammatory process that could be attributed to viral proteins. Several studies have demonstrated the role of viral proteins on vascular remodeling. A composite of chronic inflammatory changes mediated by cytokines and growth factors along with several inciting risk factors such as Hepatitis C virus (HCV) coinfection, genetic factors, male predominance, illegal drug usage, and duration of HIV infection have led to molecular changes that result in an initial phase of apoptosis followed by the formation of apoptotic resistant hyperproliferative ECs with altered phenotype. This study aims to identify the risk factors and mechanisms behind HIV-PAH pathobiology at the host-pathogen interface at the intracellular level.

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“…Patients with viral loads > 500 copies/mL and CD4 + cell counts < 200 cells/uL have a higher prevalence of increased pulmonary artery systolic pressures ≥40 mmHg and mortality than uninfected patients (17). While the presence of HIV seems a common denominator in HIV-PH (18,19), the mechanisms of how HIV causes or contributes to PH remain undeciphered. The use of animal models in both HIV and PH research areas has filled several gaps in knowledge regarding infectious HIV and/or HIV proteins as pathogenic insults to the lungs.…”

Section: Introductionmentioning

confidence: 99%

Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension

et al. 2022

Self Cite

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People living with HIV and who receive antiretroviral therapy have a significantly improved lifespan, compared to the early days without therapy. Unfortunately, persisting viral replication in the lungs sustains chronic inflammation, which may cause pulmonary vascular dysfunction and ultimate life-threatening Pulmonary Hypertension (PH). The mechanisms involved in the progression of HIV and PH remain unclear. The study of HIV-PH is limited due to the lack of tractable animal models that recapitulate infection and pathobiological aspects of PH. On one hand, mice with humanized immune systems (hu-mice) are highly relevant to HIV research but their suitability for HIV-PH research deserves investigation. On another hand, the Hypoxia-Sugen is a well-established model for experimental PH that combines hypoxia with the VEGF antagonist SU5416. To test the suitability of hu-mice, we combined HIV with either SU5416 or hypoxia. Using right heart catheterization, we found that combining HIV+SU5416 exacerbated PH. HIV infection increases human pro-inflammatory cytokines in the lungs, compared to uninfected mice. Histopathological examinations showed pulmonary vascular inflammation with arterial muscularization in HIV-PH. We also found an increase in endothelial-monocyte activating polypeptide II (EMAP II) when combining HIV+SU5416. Therefore, combinations of HIV with SU5416 or hypoxia recapitulate PH in hu-mice, creating well-suited models for infectious mechanistic pulmonary vascular research in small animals.

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Impact of human immunodeficiency virus on pulmonary vascular disease

Cited by 9 publications

References 228 publications

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

An Outlook on the Etiopathogenesis of Pulmonary Hypertension in HIV

Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension

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