High Prevalence of Pulmonary Arterial Hypertension in a Cohort of Asymptomatic HIV-Infected Patients

Isasti, Guillermo; Moreno, Tamara; Pérez, Isabel; Cabrera, Fernando; Palacios, Rosario; Santos, Jesús

doi:10.1089/aid.2012.0166

Cited by 39 publications

(35 citation statements)

References 24 publications

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“…However, recent reports claim the prevalence of PAH ranging from 2.6 to 15.5% in HIV-infected patients (3–7). In the past decade, the use of antiretroviral therapy gained importance in effectively suppressing HIV replication and increasing the life expectancy of HIV-infected individuals.…”

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confidence: 99%

Macrophage‐derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse

Sharma¹,

Chinnappan²,

Agarwal³

et al. 2018

FASEB j.

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Our previous studies consistently demonstrate enhanced pulmonary vascular remodeling in HIV–infected intravenous drug users, and in simian immunodeficiency virus–infected macaques or HIV-transgenic rats exposed to opioids or cocaine. Although we reported an associated increase in perivascular inflammation, the exact role of inflammatory cells in the development of pulmonary vascular remodeling remains unknown. In this study, HIV–infected and cocaine (H+C)–treated human monocyte derived macrophages released a higher number of extracellular vesicles (EVs), compared to HIV-infected or uninfected cocaine-treated macrophages, with a significant increase in the particle size range to 100–150 nm. Treatment of primary human pulmonary arterial smooth muscle cells (HPASMCs) with these EVs resulted in a significant increase in smooth muscle proliferation. We also observed a significant increase in the miRNA-130a level in the EVs derived from H+C-treated macrophages that corresponded with the decrease in the expression of phosphatase and tensin homolog and tuberous sclerosis 1 and 2 and activation of PI3K/protein kinase B signaling in HPASMCs on addition of these EVs. Transfection of HPASMCs with antagomir-130a–ameliorated the EV-induced effect. Thus, we conclude that EVs derived from H+C-treated macrophages promote pulmonary smooth muscle proliferation by delivery of its prosurvival miRNA cargo, which may play a crucial role in the development of PAH.—Sharma, H., Chinnappan, M., Agarwal, S., Dalvi, P., Gunewardena, S., O’Brien-Ladner, A., Dhillon, N. K. Macrophage-derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse.

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confidence: 99%

Macrophage‐derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse

Sharma¹,

Chinnappan²,

Agarwal³

et al. 2018

FASEB j.

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“…Pulmonary hypertension was present in five patients (2.6%) and 14 were in the gray zone (PASP of 36-40 mm Hg); all data about pulmonary hypertension in this cohort have been detailed elsewhere. 15 Concerning the LV parameters, the Patients with antiretroviral therapy. Quantitative variables are expressed as mean -standard deviation and qualitative variables are expressed as n (%).…”

Section: Resultsmentioning

confidence: 99%

Echocardiographic Abnormalities and Associated Factors in a Cohort of Asymptomatic HIV-Infected Patients

Isasti

Pérez

Moreno

et al. 2013

AIDS Research and Human Retroviruses

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HIV patients have been reported to have a greater prevalence of echocardiographic abnormalities. We aimed to determine the prevalence of these abnormalities and their associated factors. This was an observational study of a cohort of asymptomatic HIV patients. Data were recorded on factors of cardiovascular interest and those related to HIV infection. All the subjects underwent a transthoracic echocardiogram. The study included 196 patients, 85.2% men, mean age 46.4 years, with a mean duration of HIV infection of 123.8 months and 27.6% with AIDS. Of the patients, 94.4% were on antiretroviral therapy and 92.5% of these had an undetectable viral load. The mean CD4 cell count was 544/mm(3). The following echocardiographic abnormalities were found: left ventricular (LV) hypertrophy 28.6%, LV diastolic dysfunction 19.9%, left atrial (LA) dilatation 7.7%, right ventricular (RV) systolic dysfunction 6.1%, pulmonary hypertension 2.6%, RV dilatation 2%, and (LV) systolic dysfunction 1%. LV hypertrophy was associated with diabetes mellitus (OR 5.3, 95% CI 1.8-15.3; p=0.001), LV diastolic dysfunction with age (OR for each extra 5 years 4.4, 95% CI 4.2-4.6; p=0.0001), obesity (OR 4.07, 95% CI 1.6-10.0; p=0.02), alcohol consumption (OR 2.5, 95% CI 1.07-6.2; p=0.03) and lower CD4 cell count (OR for each 10 CD4 cells less 10.02, 95% CI 10.00-10.04; p=0.008), and RV systolic dysfunction with hypertension (OR 5.4, 95% CI 1.6-18.2; p=0.005). Echocardiographic abnormalities in HIV patients were common, especially LV hypertrophy and diastolic dysfunction. Prospective comparative studies involving the general population are needed to determine the prevalence of HIV infection and its treatment in these abnormalities.

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“…Levels of T-cell activation and innate system activation are often higher than that observed in well-matched uninfected adults (5,6). These persistent abnormalities may contribute to abnormal vaccine responses (7,8), a higher than normal incidence of non-AIDS-related cancers (9,10) and increased risk for clinical conditions associated with chronic inflammation (e.g., cardiac disease, clotting disorders, pulmonary hypertension, emphysema, and stroke) (11)(12)(13)(14)(15)(16)(17)(18). Thus, improvements over current approaches to treatment of HIV infection that more fully restore normal immune function might significantly improve health and life expectancy.…”

mentioning

confidence: 99%

Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues

Fletcher

Staskus²,

Wietgrefe³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

581

608

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Antiretroviral therapy can reduce HIV-1 to undetectable levels in peripheral blood, but the effectiveness of treatment in suppressing replication in lymphoid tissue reservoirs has not been determined. Here we show in lymph node samples obtained before and during 6 mo of treatment that the tissue concentrations of five of the most frequently used antiretroviral drugs are much lower than in peripheral blood. These lower concentrations correlated with continued virus replication measured by the slower decay or increases in the follicular dendritic cell network pool of virions and with detection of viral RNA in productively infected cells. The evidence of persistent replication associated with apparently suboptimal drug concentrations argues for development and evaluation of novel therapeutic strategies that will fully suppress viral replication in lymphatic tissues. These strategies could avert the long-term clinical consequences of chronic immune activation driven directly or indirectly by low-level viral replication to thereby improve immune reconstitution.drug levels | pharmacokinetics | FDC network C ombination antiviral therapy (ART) to suppress HIV-1 replication and reduce plasma viremia to below the limits of detection in peripheral blood (PB) has reduced mortality and dramatically improved quality of life for patients. However, immune reconstitution, measured by changes in the size of populations of CD4 T cells, is often incomplete, even after years of therapy (1-3). During apparently effective therapy, CD4 T-cell populations in PB mononuclear cells (PBMCs), lymph node (LN), and gut-associated lymphoid tissue (GALT) remain abnormally low and innate and adaptive immunity is not fully restored (4). Levels of T-cell activation and innate system activation are often higher than that observed in well-matched uninfected adults (5, 6). These persistent abnormalities may contribute to abnormal vaccine responses (7, 8), a higher than normal incidence of non-AIDS-related cancers (9, 10) and increased risk for clinical conditions associated with chronic inflammation (e.g., cardiac disease, clotting disorders, pulmonary hypertension, emphysema, and stroke) (11-18). Thus, improvements over current approaches to treatment of HIV infection that more fully restore normal immune function might significantly improve health and life expectancy.To that end, we explore here the hypothesis that antiretroviral drug (ARV) concentrations might be insufficient to fully suppress replication in the lymphoid tissue compartments, which are the principal sites where virus is produced, stored as complexes on the follicular dendritic cell network (FDCn) (19-21), and persists in latently infected cells during ART (19,20,22). This hypothesis builds first on the link between the size of the reservoir and the degree of inflammation, arguing that persistent virus production during ART could sustain immune activation (IA) and downstream pathological consequences (23, 24), and second on drug distribution studies in animal models of AIDS in which ...

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High Prevalence of Pulmonary Arterial Hypertension in a Cohort of Asymptomatic HIV-Infected Patients

Cited by 39 publications

References 24 publications

Macrophage‐derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse

Macrophage‐derived extracellular vesicles mediate smooth muscle hyperplasia: role of altered miRNA cargo in response to HIV infection and substance abuse

Echocardiographic Abnormalities and Associated Factors in a Cohort of Asymptomatic HIV-Infected Patients

Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues

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