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Purpose of ReviewThe main goal of this article is to discuss the role of the epithelial sodium channel (ENaC) in extracellular fluid and blood pressure regulation.Recent FindingsBesides its role in sodium handling in the kidney, recent studies have found that ENaC expressed in other cells including immune cells can influence blood pressure via extra-renal mechanisms. Dendritic cells (DCs) are activated and contribute to salt-sensitive hypertension in an ENaC-dependent manner. We discuss recent studies on how ENaC is regulated in both the kidney and other sites including the vascular smooth muscles, endothelial cells, and immune cells. We also discuss how this extra-renal ENaC can play a role in salt-sensitive hypertension and its promise as a novel therapeutic target.SummaryThe role of ENaC in blood pressure regulation in the kidney has been well studied. Recent human gene sequencing efforts have identified thousands of variants among the genes encoding ENaC, and research efforts to determine if these variants and their expression in extra-renal tissue play a role in hypertension will advance our understanding of the pathogenesis of ENaC-mediated cardiovascular disease and lead to novel therapeutic targets.

Purpose of ReviewSalt sensitivity of blood pressure (SSBP) is an independent predictor of death due to cardiovascular events and affects nearly 50% of the hypertensive and 25% of the normotensive population. Strong evidence indicates that reducing sodium (Na+) intake decreases blood pressure (BP) and cardiovascular events. The precise mechanisms of how dietary Na+ contributes to elevation and cardiovascular disease remain unclear. The goal of this review is to discuss mechanisms of salt-induced cardiovascular disease and how the microbiome may play a role.Recent FindingsThe innate and adaptive immune systems are involved in the genesis of salt-induced hypertension. Mice fed a high-salt diet exhibit increased inflammation with a marked increase in dendritic cell (DC) production of interleukin (IL)-6 and formation of isolevuglandins (IsoLG)-protein adducts, which drive interferon-gamma (IFN-γ) and IL-17A production by T cells. While prior studies have mainly focused on the brain, kidney, and vasculature as playing a role in salt-induced hypertension, the gut is the first and largest location for Na+ absorption. Research from our group and others strongly suggests that the gut microbiome contributes to salt-induced inflammation and hypertension.SummaryRecent studies suggest that alterations in the gut microbiome contribute to salt-induced hypertension. However, the contribution of the microbiome to SSBP and its underlying mechanisms are not known. Targeting the microbiota and the associated immune cell activation could conceivably provide the much-needed therapy for SSBP.

Vasohibins (VASHs), comprising VASH-1 and VASH-2, were initially identified as regulators of angiogenesis. Recent studies, however, have unveiled their novel role in fibrosis and microtubule detyrosination. The dysregulated expression of VASHs is associated with several pathological processes, such as angiogenesis dysfunction, microtubule detyrosination, and fibrosis, contributing to various diseases. These findings suggest the pleiotropic effects of VASHs in multiple organs and systems beyond angiogenesis. This review explores the molecular properties of VASHs and their emerging functions in tubulin carboxyl activity and microtubule detyrosination—key to brain and cardiac remodeling. We also discuss the potential therapeutic applications of their interference in diseases such as tumorigenesis, as well as renal-, reproductive-, and liver-related diseases.

Vascular oxidative injury accompanies many common conditions associated with hypertension. In the present study, we employed mouse models with excessive vascular production of ROS (tg(sm/p22phox) mice, which overexpress the NADPH oxidase subunit p22(phox) in smooth muscle, and mice with vascular-specific deletion of extracellular SOD) and have shown that these animals develop vascular collagen deposition, aortic stiffening, renal dysfunction, and hypertension with age. T cells from tg(sm/p22phox) mice produced high levels of IL-17A and IFN-γ. Crossing tg(sm/p22phox) mice with lymphocyte-deficient Rag1(-/-) mice eliminated vascular inflammation, aortic stiffening, renal dysfunction, and hypertension; however, adoptive transfer of T cells restored these processes. Isoketal-protein adducts, which are immunogenic, were increased in aortas, DCs, and macrophages of tg(sm/p22phox) mice. Autologous pulsing with tg(sm/p22phox) aortic homogenates promoted DCs of tg(sm/p22phox) mice to stimulate T cell proliferation and production of IFN-γ, IL-17A, and TNF-α. Treatment with the superoxide scavenger tempol or the isoketal scavenger 2-hydroxybenzylamine (2-HOBA) normalized blood pressure; prevented vascular inflammation, aortic stiffening, and hypertension; and prevented DC and T cell activation. Moreover, in human aortas, the aortic content of isoketal adducts correlated with fibrosis and inflammation severity. Together, these results define a pathway linking vascular oxidant stress to immune activation and aortic stiffening and provide insight into the systemic inflammation encountered in common vascular diseases.

The development of antiretroviral drugs (ARVs) was a great milestone in the management of HIV infection. ARVs suppress viral activity in the host cell, thus minimizing injury to the cells and prolonging life. However, an effective treatment has remained elusive for four decades due to the successful immune evasion mechanisms of the virus. A thorough understanding of the molecular interaction of HIV with the host cell is essential in the development of both preventive and curative therapies for HIV infection. This review highlights several inherent mechanisms of HIV that promote its survival and propagation, such as the targeting of CD4+ lymphocytes, the downregulation of MHC class I and II, antigenic variation and an envelope complex that minimizes antibody access, and how they collaboratively render the immune system unable to mount an effective response.

Purpose of ReviewWith the advent of highly active antiretroviral therapy (ART), the life span of persons with HIV (PWH) has been nearly normalized. With aging, prevalence of the metabolic syndrome (MetS), including hypertension, has increased in the HIV population and exceeds that in the general population in some studies. This is due to a combination of traditional risk factors in addition to the effects attributable to the virus and ART. We review recent findings on the mechanisms contributing to MetS and hypertension in PWH, particularly those specific to the viral infection and to ART.Recent FindingsActivation of the renin-angiotensin-aldosterone system (RAAS) and chronic immune activation contribute to the development of MetS and hypertension in PWH. HIV proteins and some ART agents alter adipocyte health contributing to dyslipidemias, weight gain, and insulin resistance. HIV infection also contributes to hypertension by direct effects on the RAAS that intertwine with inflammation by the RAAS also contributing to T cell activation.SummaryRecent data suggest that in addition to current ART, therapeutic targeting of the MetS and hypertension in PWH, by interfering with the RAAS, treating insulin resistance directly or by use of immunomodulators that dampen inflammation, may be critical for preventing or treating these risk factors and to improve overall cardiovascular complications in the HIV-infected aging population.

Salt sensitivity is a well-recognized contributor to cardiovascular risk, traditionally linked to elevated blood pressure. However, emerging evidence suggests that high dietary sodium may also promote myocardial fibrosis through non-hemodynamic mechanisms, including the activation of redox-sensitive and profibrotic pathways. Despite growing mechanistic insights, the connection between salt sensitivity and myocardial fibrosis remains underexplored, particularly in human studies. This review synthesizes current experimental and translational evidence linking dietary salt intake to myocardial fibrosis, with a focus on molecular signaling cascades, tissue sodium compartmentalization, and the clinical implications of salt-sensitive physiology. We discuss the relevance of these mechanisms to the development of diastolic dysfunction and their potential contribution to heart failure with preserved ejection fraction (HFpEF). In addition, we highlight findings from animal models and the emerging application of sodium magnetic resonance imaging ( 23 Na-MRI) as a novel imaging tool for visualizing myocardial sodium overload and its association with fibrotic remodeling. Finally, we explore future therapeutic strategies that extend beyond traditional antihypertensives, including mineralocorticoid receptor antagonists (MRAs), angiotensin receptor blockers (ARBs), sodium-glucose cotransport 2 (SGLT2) inhibitors, and sodium-modulating interventions. Together, these insights offer new opportunities for early detection and targeted treatment in salt-sensitive cardiovascular disease.

Purpose of ReviewTo systematically review recent findings on the role of immune cell activation in the pathogenesis of hypertension in people living with HIV (PLWH) and compare studies from Sub-Saharan Africa with what is reported in the USA and European literature according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Recent FindingsPLWH have an increased risk for development of hypertension and cardiovascular disease. Chronic immune activation contributes to hypertension but the inflammatory milieu that predisposes PLWH to hypertension is poorly understood. We identified 45 relevant studies from 13 unique African countries. The prevalence of hypertension in PLWH on antiretroviral therapy (ART) and the ART-naive PLWH ranged from 6 to 50% and 2 to 41%, respectively. Interleukin (IL)-17A, interferon (IFN)-γ, and higher CD4+ T cell counts were associated with hypertension in ART-treated participants.SummaryTargeting adaptive immune activation could provide improved care for hypertensive PLWH. Further research is needed to characterize the inflammatory milieu contributing to hypertension in PLWH especially in African populations where the global burden of HIV is the highest.

Preeclampsia (PE) is a significant obstetric complication associated with adverse maternal and fetal outcomes. Zambia, like several Sub-Saharan African nations, experiences a high prevalence of pregnancy-related hypertension, with PE being a major contributor to maternal and foetal mortality. This study aimed to identify the factors associated with the development of PE. We conducted a cross-sectional study at Livingstone University Teaching Hospital in Zambia (LUTH). PE was defined as new-onset hypertension with systolic blood pressure [greater than or equal to]140 mmHg or diastolic blood pressure [greater than or equal to]90 mmHg occurring after 20 weeks of gestation, accompanied by proteinuria with dipstick reading of 1 + . Data from patients' most recent hospital visits was collected by trained research assistants using medical record abstraction. A total of 1018 participants were included. Demographic, clinical, and haematological parameters were analysed. We conducted both descriptive and inferential analyses using Stata version 17. Univariable and multivariable logistic regression were employed to investigate factors associated with PE. The median age of participants was 27 years (IQR: 21-33). The prevalence of PE was 12.2% (n = 124). Among the 17.7% (n = 172) of participants who were employed, 19.1% (n = 33) had PE. Factors positively associated with PE included increasing age (Adjusted Odds Ratio [AOR]: 1.07, 95% Confidence Interval [CI]: 1.02-1.12, p = 0.002), a previous history of PE (AOR: 30.8, 95% CI: 8.7-108.6, p < 0.001), and a family history of PE (AOR: 9.97, 95% CI: 2.53-39.27, p = 0.001). Conversely, a unit (week) increase in gestational age was negatively associated with PE (AOR: 0.89, 95% CI: 0.83-0.97, p = 0.007). This study identifies maternal age, family history, and prior obstetric history as key associated factors for PE, emphasizing the need for targeted screening and early intervention. Enhanced prenatal care, including routine risk assessments, patient education, and regular monitoring through blood pressure checks, urine protein testing, and fetal growth assessments, is cardinal for early detection and effective management of high-risk individuals.

Preeclampsia (PE) is a significant obstetric complication associated with adverse maternal and fetal outcomes. Zambia, like several Sub-Saharan African nations, experiences a high prevalence of pregnancy-related hypertension, with PE being a major contributor to maternal and foetal mortality. This study aimed to identify the factors associated with the development of PE. We conducted a cross-sectional study at Livingstone University Teaching Hospital in Zambia (LUTH). PE was defined as new-onset hypertension with systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg occurring after 20 weeks of gestation, accompanied by proteinuria with dipstick reading of 1 + . Data from patients' most recent hospital visits was collected by trained research assistants using medical record abstraction. A total of 1018 participants were included. Demographic, clinical, and haematological parameters were analysed. We conducted both descriptive and inferential analyses using Stata version 17. Univariable and multivariable logistic regression were employed to investigate factors associated with PE. The median age of participants was 27 years (IQR: 21-33). The prevalence of PE was 12.2% (n = 124). Among the 17.7% (n = 172) of participants who were employed, 19.1% (n = 33) had PE. Factors positively associated with PE included increasing age (Adjusted Odds Ratio [AOR]: 1.07, 95% Confidence Interval [CI]: 1.02-1.12, p = 0.002), a previous history of PE (AOR: 30.8, 95% CI: 8.7-108.6, p < 0.001), and a family history of PE (AOR: 9.97, 95% CI: 2.53-39.27, p = 0.001). Conversely, a unit (week) increase in gestational age was negatively associated with PE (AOR: 0.89, 95% CI: 0.83-0.97, p = 0.007). This study identifies maternal age, family history, and prior obstetric history as key associated factors for PE, emphasizing the need for targeted screening and early intervention. Enhanced prenatal care, including routine risk assessments, patient education, and regular monitoring through blood pressure checks, urine protein testing, and fetal growth assessments, is cardinal for early detection and effective management of high-risk individuals.