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Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease characterized by the progressive elevation of pulmonary arterial pressures. It is becoming increasingly apparent that inflammation contributes to the pathogenesis and progression of PAH. Several viruses are known to cause PAH, such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human endogenous retrovirus K(HERV-K), and human immunodeficiency virus (HIV), in part due to acute and chronic inflammation. In this review, we discuss the connections between HERV-K, HIV, SARS-CoV-2, and PAH, to stimulate research regarding new therapeutic options and provide new targets for the treatment of the disease. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is associated with significant morbidity and mortality. RASA3 is a GTPase activating protein integral to angiogenesis and endothelial barrier function. In this study, we explore the association of RASA3 genetic variation with PH risk in patients with sickle cell disease (SCD)- associated PH and pulmonary arterial hypertension (PAH). Cis-expression quantitative trait loci (eQTL) were queried for RASA3 using whole genome genotype arrays and gene expression profiles derived from peripheral blood mononuclear cells (PBMC) of three SCD cohorts. Genome-wide single nucleotide polymorphisms (SNPs) near or in the RASA3 gene that may associate with lung RASA3 expression were identified, reduced to 9 tagging SNPs for RASA3 and associated with markers of PH. Associations between the top RASA3 SNP and PAH severity were corroborated using data from the PAH Biobank and analyzed based on European or African ancestry (EA, AA). We found that PBMC RASA3 expression was lower in patients with SCD-associated PH as defined by echocardiography and right heart catheterization and was associated with higher mortality. One eQTL for RASA3 (rs9525228) was identified, with the risk allele correlating with PH risk, higher tricuspid regurgitant jet velocity and higher pulmonary vascular resistance in patients with SCD-associated PH. rs9525228 associated with markers of precapillary PH and decreased survival in individuals of EA but not AA. In conclusion, RASA3 is a novel candidate gene in SCDassociated PH and PAH, with RASA3 expression appearing to be protective. Further studies are ongoing to delineate the role of RASA3 in PH. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is characterized by repeated episodes of hemolysis and vaso-occlusion. Hemolysis is a risk factor for the development of pulmonary hypertension (PH), and currently SCD-related PH is classified as World Health Organization group 5 PH. Patients with SCD-related PH have unique hemodynamics, comorbidities, and phenotypes that may contribute to the development of PH. SCD-related PH is defined as a mean pulmonary artery pressure >20 mm Hg, a pulmonary artery occlusion pressure ≤15 mm Hg and relatively low pulmonary vascular resistance (PVR) (>160 dynes·sec/cm5 rather than the typical definition of ≥240 dynes·sec/cm5), an important distinction because of a baseline high-cardiac output state in the setting of chronic anemia and low vascular resistance. Diastolic dysfunction is common, and right heart catheterization is warranted to determine if combined precapillary and postcapillary PH is present. Thromboembolism is common among patients with SCD, and screening for chronic thromboembolic pulmonary hypertension is essential. There are few studies evaluating advanced therapies in this population. The mainstay of treatment includes targeting correction of their primary hemoglobinopathy as well as aggressive management of underlying comorbid conditions. SCD-related PH is common among patients with SCD and is associated with increased mortality. A high index of suspicion is warranted during evaluation to identify all potential factors that may be contributing to disease. [ABSTRACT FROM AUTHOR]