Background: Human Immunodeficiency Virus (HIV) infections remain a source of cardiopulmonary complications among people receiving antiretroviral therapy. Still to this day, pulmonary hypertension (PH) severely affects the prognosis in this patient population. The persistent expression of HIV proteins, even during viral suppression, has been implicated in vascular dysfunction; however, little is known about the specific effects of these proteins on the pulmonary vasculature. This study investigates the impact of Nef variants derived from HIV-positive pulmonary hypertensive and normotensive donors on pulmonary vascular cells in vitro. Methods: We utilized well-characterized Nef molecular constructs to examine their effects on cell adhesion molecule gene expression (ICAM1, VCAM1, and SELE), pro-apoptotic gene expression (BAX, BAK), and vasoconstrictive endothelin-1 (EDN1) gene expression in endothelial nitric oxide synthase (eNOS) nitric oxide and the production and secretion of pro-inflammatory cytokines over 24, 48, and 72 h post-transfections with Nef variants. Results: HIV Nef variants SF2, NA7, and PH-associated Fr17 and 3236 induced a significant increase in adhesion molecule gene expression of ICAM1, VCAM1, and SELE. Pulmonary normotensive Nef 1138 decreased ICAM1 gene expression, but had increased VCAM1. PH Nef ItVR showed a consistent decrease in ICAM1 and no changes in SELE and VCAM1 expression. Further gene expression analyses of pro-apoptotic genes BAX and BAK demonstrated that Nef NA7, SF2, normotensive Nef 1138, and PH Nef Fr8, Fr9, Fr17, and 3236 variants significantly increased gene expression for apoptosis. Normotensive Nef 1138, as well as PH Nef Fr9 and ItVR, all displayed a statistically significant decrease in BAX expression. The expression of EDN1 had a statistically significant increase in samples treated with Nef NA7, SF2, normotensive Nef 2044 and PH Nef 3236, Fr17, and Fr8. Notably, PH-associated Nef variants sustained pro-inflammatory cytokine production, including IL-2, IL-4, and TNFα, while anti-inflammatory cytokine levels remained insufficient. Furthermore, eNOS was transiently upregulated by all Nef variants except for normotensive Nef 2044. Conclusions: The distinct effects of Nef variants on pulmonary vascular cell biology highlight the complex interplay between Nef, host factors, and vascular pathogenesis according to the variants.

Background: Cardiovascular disease (CVD) remains the leading cause of death in the United States and Texas, with a disproportionately high impact on racial/ethnic minority and low-income populations. Methods: This cross-sectional study examined electronic medical records from 201 low-income adults served by a free preventive health screening program, operating at two non-profit social service centers and one homeless shelter in Lubbock, Texas (2022–2024), to estimate the prevalence of major CVD risk factors and assess demographic disparities. Results: Among 201 participants, 62.7% were Hispanic and 11.9% were Black. Nearly half (47.8%) exhibited elevated blood pressure consistent with hypertensive range, including a substantial proportion without a prior self-reported diagnosis. Obesity was observed in 46.3%, tobacco use in 41.8%, self-reported type 2 diabetes mellitus (T2DM) in 36.3%, and hypercholesterolemia in 15.4% of the sample. Black participants exhibited the highest rate of elevated blood pressure (62.5%). Significant demographic differences were found in the prevalence of T2DM and lipid disorders ( p < .01). Conclusion: Our findings highlight a heavy burden of CVD risk among the low-income study population residing in West Texas, particularly among racial/ethnic minorities. The high rates of elevated blood pressure consistent with hypertensive range emphasize the urgent need for culturally responsive outreach, expanded screenings, and sustained chronic disease management strategies. These data can inform public health policy and targeted interventions to reduce cardiovascular disparities in West Texas and similar underserved regions.

Background: While women are among the fastest-growing subgroups of the homeless population and have a higher prevalence of poverty than men, most studies of cardiovascular disease (CVD) risk in this vulnerable population are conducted primarily among men. We evaluated differences in CVD risk between men and women experiencing poverty and homelessness in West Texas, a medically underserved region. Methods: Data were collected from 152 adults (50% women) aged 30–74 years, who were seen at free health clinics. Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated. The Framingham risk algorithm was used to estimate the risk for incident CVD in the next 10 years. Results: The mean age of participants was 55.3 years. The prevalence of CVD risk factors was high among participants and tended to be similar between men and women: diabetes (34%), current smokers (47%), obesity (50%), and hypertension (83%). After controlling for demographic factors, behavior/lifestyle factors, and health conditions, the high (>20%) 10-year risk of CVD was two-fold higher among men (PR: 2.41, 95%CI: 1.75–3.32). While the association was consistent among men regardless of the number of comorbid conditions, among women, those with three or more comorbid conditions had an elevated 10-year risk for CVD compared to those with no comorbid conditions (PR: 11.68, 95%CI: 1.88–72.60, p interaction = 0.001). Conclusions: This study found that CVD risk was elevated among poor and homeless adults, with men having a higher risk than women. Comorbid conditions had a greater impact on women than men who were at high risk for CVD.

Little is known about the manifestation of cardiovascular diseases (CVD) among individuals with ocular cancer (OC), a population for whom reports on sex-based differences in survival remain inconsistent. We evaluated the occurrence of CVD mortality after the diagnosis of OC in the United States. We used data from 11,460 adults diagnosed with OC from 2000 to 2021 who were ≥18 years and were enrolled in the Surveillance, Epidemiology, and End Results program. We used competing risk models to estimate hazard ratios (HR) and 95% confidence intervals (CI). About 55% of adults were male, with uveal melanoma being the most common OC (72.1%). During a median follow-up of 5.4 years, 4561 deaths occurred, with 15% attributable to CVD. In models adjusted for sociodemographic and clinico-pathophysiological factors, male adults had elevated risk for CVD mortality (HR: 1.54, 95%CI: 1.31–1.81). The sex difference in CVD mortality was more prominent for adults diagnosed with OC before 65 years of age (HR: 2.15; 95%CI: 1.48–3.11). These associations remained largely unchanged in propensity score analysis. In this study of adults with OC, CVD deaths were higher among young and middle-aged males. Implementation of optimal cardiovascular health interventions after diagnosis of OC, especially among men, holds promise in enhancing survival in this population.

Rationale: The risk of developing severe pulmonary vascular diseases such as pulmonary hypertension (PH) heightens upon infection with Human Immunodeficiency Virus (HIV). How HIV specifically exacerbates pulmonary vascular remodeling is unknown. Previous studies demonstrated the association between HIV Nef variants and pulmonary vascular disease. Here, we investigated the differential impact of HIV Nef variants from HIV-positive pulmonary normotensive and hypertensive donors on endothelial nitric oxide synthase (eNOS) production, nitric oxide (NO) production, and pro-inflammatory cytokine secretion. Methods: HIV nef isolates cloned into HaloTag vectors (Promega) were used to transfect primary arterial endothelial cells co-cultured with smooth muscle cells (Lonza) to mimic pulmonary vascular cell crosstalk. Cell cultures were maintained at 37ºC, 5% CO2. Diaminofluorescein-2 diacetate (DAF-2 DA) was added to cells and intracellular NO production was measured using microplate fluorescence reader (Tecan) to quantify green fluorescence intensity at 24- and 48-hours post-transfection. The release of eNOS was measured by ELISA at 24-, 48-, and 72-hours post-transfection of pulmonary vascular cells with Nef molecular constructs. Cell culture supernatants were collected and analyzed for pro-inflammatory cytokine levels (Meso Scale Discovery). Results: Hypertensive Nef variants significantly decreased NO production at 24 hours and remained impaired at 48 hours. NO levels in cells transfected with Nef derived from a normotensive donor were significantly increased at both time points (p < 0.01). Across all conditions, NO levels were higher at 48 hours compared to 24 hours. Nef-transfected samples showed statistically significant decreases in eNOS after 24 hours, showing the time-dependent effect of eNOS expression. Deficient NO production, which impairs vasodilation, contributes to the development of PH. eNOS level are also known to be reduced in PH patients. This reduction in nitric oxide production and eNOS levels seen in hypertensive Nef variants supports the notion that HIV-Nef causes oxidative stress that may lead to vascular dysfunction. Nef variants derived from pulmonary hypertensive patients sustained pro-inflammatory cytokine production, including IL-2, IL-4, IL-13, IFNγ and TNFα. This increase in mediators of vascular inflammation suggest that sustained inflammation within the pulmonary vascular microenvironment may trigger endothelial dysfunction and disease progression. Conclusions/Future Directions: The distinct effects of Nef variants on pulmonary vascular cell biology highlight the intricate interplay between Nef and vascular pathogenesis according to the variants. Future efforts include challenging the pulmonary vasculature in vivo, using our HIV-infected humanized mouse model followed by evaluation of differential vascular hemodynamics induced by Nef variants present in patients with/without pulmonary vascular disease.