Human Immunodeficiency Virus–Associated Pulmonary Arterial Hypertension

Butrous, Ghazwan

doi:10.1161/circulationaha.114.006978

Cited by 43 publications

(17 citation statements)

References 101 publications

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“…Epidemiological studies have shown that the incidence of PAH in HIV(+) individuals is ~25-fold higher compared with that in HIV(−) subjects, indicating thereby a strong positive association between HIV infection and PAH 9 , 10 . Several previous studies have demonstrated that HIV infection coincided with the development of pulmonary vascular diseases, including severe PAH 11 , 12 . Attempts aimed at identifying mature HIV particles in the lung tissue however, have failed despite use of multiple technological approaches, such as electron microscopy, immunohistochemistry, DNA in situ hybridization, and polymerase chain reaction 13 , 14 .…”

Section: Introductionmentioning

confidence: 97%

Notch3/VEGF-A axis is involved in TAT-mediated proliferation of pulmonary artery smooth muscle cells: Implications for HIV-associated PAH

et al. 2018

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The incidence of pulmonary arterial hypertension (PAH) is a significant co-morbidity observed in HIV (+) individuals. Pulmonary artery smooth muscle cells (PASMCs)—key components of the arterial vessel wall that regulate vessel diameter, demonstrate increased proliferation and hypertrophy in the lungs of HIV infected individuals, underscoring the role of these cells in the pathogenesis of HIV-associated PAH. While several pathways have been implicated in enhanced proliferation of PASMCs, detailed molecular mechanism(s) underlying HIV-associated PASMC proliferation still remain elusive. In the current study, we sought to investigate the effects HIV protein transactivator of transcription (TAT)-mediated proliferation on PASMCs. In agreement with earlier findings, our results also demonstrated TAT-mediated proliferation of human PASMCs. We identified activation of a novel Notch3 signaling pathway in TAT-mediated proliferation of PASMCs. Further validation of the Notch 3 pathway was demonstrated using both pharmacological (γ-secretase inhibitor, DAPT), as well as genetic approaches (Notch3 siRNA). Vascular endothelial growth factor A (VEGF-A) was identified as a novel downstream molecule that was induced following Notch activation. Findings from in vitro studies were further validated in archived simian immunodeficiency virus (SIV)-infected monkey lung tissues. There was increased activation of Notch3 signaling as well as enhanced expression of VEGF-A in the lungs of SIV-infected macaques compared with the lungs of SIV(−) controls. Taken together, we demonstrated that HIV-TAT increased the proliferation of PASMCs via the Notch3/VEGF-A axis. Targeting the Notch3/VEGF-A axis could thus be considered a potential therapeutic approach for the treatment of HIV-associated PAH.

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Section: Introductionmentioning

confidence: 97%

Notch3/VEGF-A axis is involved in TAT-mediated proliferation of pulmonary artery smooth muscle cells: Implications for HIV-associated PAH

et al. 2018

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“…Careful analysis of the published data suggests that the estimated prevalence of HIV-pulmonary hypertension ranges from 0.4 to 11.5% globally 135,136 . The true prevalence of clinical pulmonary hypertension in HIV patients is likely to vary according to regional differences because of differences in environmental, cultural, and genetic factors 135 . The condition can be exacerbated by using addictive drugs found in many herbal remedies in the developing regions 137 .…”

Section: Viral Infectionmentioning

confidence: 99%

Pulmonary hypertension: From an orphan disease to a global epidemic

Butrous

2020

gcsp

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[No abstract. Showing first paragraph of article]Pulmonary hypertension is a progressive disease characterized by an elevation of pulmonary artery pressure and pulmonary vascular resistance, leading to right ventricular failure and death. It remains a challenging chronic progressive disease, but the current interest and advent of medical therapy in the last 20 years has significantly changed the perception of medical community in this disease. Pulmonary hypertension is not a specific disease; the majority of cases present with other diseases and various pathological processes that affect the pulmonary vasculature, and consequently increase pulmonary pressure and vascular resistance.

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“…According to a systematic review, the prevalence of PAH among HIV-infected individuals presenting with cardiovascular symptoms from Africa is as high as 14% [49], but the number of studies included was very small. Schistosomiasis (see below), which is independently associated with PAH [47, 50], and other concurrent chronic lung diseases could also contribute to an increased burden of PAH in low-income settings [51]. The true prevalence of HIV-related PAH is however difficult to ascertain due to differences in methods used for establishing the diagnosis.…”

Section: Hiv Infection and The Lungmentioning

confidence: 99%

“…Transthoracic echocardiography tends to overestimate the prevalence and cannot accurately evaluate pulmonary vascular pressures [46]. Patients with HIV-related PAH are likely to benefit from the same therapies as non-HIV patients [50]. However, physicians should note that there are drug interactions between phosphodiesterase type V inhibitors such as sildenafil and protease inhibitors [52].…”

Section: Hiv Infection and The Lungmentioning

confidence: 99%

Pulmonary Diseases in Refugees and Migrants in Europe

et al. 2018

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More than 2 million people fleeing conflict, persecution, and poverty applied for asylum between 2015 and 2016 in the European Union. Due to this, medical practitioners in recipient countries may be facing a broader spectrum of conditions and unusual presentations not previously encountered, including a wide range of infections with pulmonary involvement. Tuberculosis is known to be more common in migrants and has been covered broadly in other publications. The scope of this review was to provide an overview of exotic infections with pulmonary involvement that could be encountered in refugees and migrants and to briefly describe their epidemiology, diagnosis, and management. As refugees and migrants travel from numerous countries and continents, it is important to be aware of the various organisms that might cause disease according to the country of origin. Some of these diseases are very rare and geographically restricted to certain regions, while others have a more cosmopolitan distribution. Also, the spectrum of severity of these infections can vary from very benign to severe and even life-threatening. We will also describe infectious and noninfectious complications that can be associated with HIV infection as some migrants might originate from high HIV prevalence countries in sub-Saharan Africa. As the diagnosis and treatment of these diseases can be challenging in certain situations, patients with suspected infection might require referral to specialized centers with experience in their management. Additionally, a brief description of noncommunicable pulmonary diseases will be provided.

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Human Immunodeficiency Virus–Associated Pulmonary Arterial Hypertension

Cited by 43 publications

References 101 publications

Notch3/VEGF-A axis is involved in TAT-mediated proliferation of pulmonary artery smooth muscle cells: Implications for HIV-associated PAH

Notch3/VEGF-A axis is involved in TAT-mediated proliferation of pulmonary artery smooth muscle cells: Implications for HIV-associated PAH

Pulmonary hypertension: From an orphan disease to a global epidemic

Pulmonary Diseases in Refugees and Migrants in Europe

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