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. 2016 Jan 11;11(1):e0146355.
doi: 10.1371/journal.pone.0146355. eCollection 2016.

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection

Rushi V Parikh  1 , Yifei Ma  2 , Rebecca Scherzer  3 , Amanda S Heringer  4 , John S Macgregor  4 , Jeffrey N Martin  5 , Steven G Deeks  6 , Peter Ganz  4 , Priscilla Y Hsue  4
Affiliations

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection

Rushi V Parikh et al. PLoS One. .

Abstract

Background: HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.

Methods: We measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.

Results: Among 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.

Conclusions: Higher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH.

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Conflict of interest statement

Competing Interests: PYH has received honoraria from Gilead. RS has received an honorarium from Merck. The remaining authors declare no conflicts of interest. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Proposed Mechanism by which ET-1 Contributes to the Development of HIV-Associated PAH.
ET-1, endothelin-1; PAH, pulmonary arterial hypertension.
See this image and copyright information in PMC

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