Aims: Excess dietary sodium intake and retention lead to hypertension. Impaired dermal lymphangiogenesis and lymphatic dysfunction-mediated sodium and fluid imbalance are pathological mechanisms. The adenosine A2A receptor (A2AR) is expressed in lymphatic endothelial cells (LECs), while the roles and mechanisms of LEC-A2AR in skin lymphangiogenesis during salt-induced hypertension are not clear.
Methods And Results: The expression of LEC-A2AR correlated with lymphatic vessel density in both high-salt diet (HSD)-induced hypertensive mice and hypertensive patients. Lymphatic endothelial cell-specific A2AR knockout mice fed HSD exhibited 17 ± 2% increase in blood pressure and 17 ± 3% increase in Na+ content associated with decreased lymphatic density (-19 ± 2%) compared with HSD-WT mice. A2AR activation by agonist CGS21680 increased lymphatic capillary density and decreased blood pressure in HSD-WT mice. Furthermore, this A2AR agonist activated MSK1 directly to promote VEGFR2 activation and endocytosis independently of VEGF as assessed by phosphoprotein profiling and immunoprecipitation assays in LECs. VEGFR2 kinase activity inhibitor fruquintinib or VEGFR2 knockout in LECs but not VEGF-neutralizing antibody bevacizumab suppressed A2AR activation-mediated decrease in blood pressure. Immunostaining revealed phosphorylated VEGFR2 and MSK1 expression in the LECs were positively correlated with skin lymphatic vessel density and A2AR level in hypertensive patients.
Conclusion: The study highlights a novel A2AR-mediated VEGF-independent activation of VEGFR2 signaling in dermal lymphangiogenesis and sodium balance, which might be a potential therapeutic target in salt-sensitive hypertension.
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http://dx.doi.org/10.1093/eurheartj/ehad377 | DOI Listing |
Gut Microbes
December 2025
Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash, Clayton, Australia.
The gut microbiota is a crucial link between diet and cardiovascular disease (CVD). Using fecal metaproteomics, a method that concurrently captures human gut and microbiome proteins, we determined the crosstalk between gut microbiome, diet, gut health, and CVD. Traditional CVD risk factors (age, BMI, sex, blood pressure) explained < 10% of the proteome variance.
View Article and Find Full Text PDFGut Pathog
December 2024
Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Background: Maintaining gut microbial homeostasis is crucial for human health, as imbalances in the gut microbiota (GM) can lead to various diseases, including metabolic syndrome (MS), exacerbated by the use of antipsychotic medications such as olanzapine (OLZ). Understanding the role of the GM in OLZ-induced MS could lead to new therapeutic strategies. This study used metagenomic analysis to explore the impact of OLZ on the GM composition and examined how probiotics can mitigate its adverse effects in a rat model.
View Article and Find Full Text PDFBMC Geriatr
December 2024
Department of Chemical Pathology, University of Calabar Teaching Hospital, Calabar, Cross River State, Nigeria.
Background: The number of people reaching old age is rising, bringing an increase in age-related diseases like cardiovascular conditions and cognitive dysfunction. Cognitive impairment (CI) impacts various brain functions, affecting daily activities and quality of life. Metabolic syndrome (MetS), a cluster of cardiovascular risk factors, has been implicated in CI.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic has led to a significant shift in healthcare services, focusing on pandemic response and emergency preparedness. The Oman Ministry of Health implemented various measures to combat and control COVID-19. However, this shift disrupted routine outpatient appointments, particularly for chronic diseases such as diabetes mellitus (DM) and hypertension (HTN).
View Article and Find Full Text PDFNeurotherapeutics
December 2024
Essex Cardiothoracic Centre, Mid and South Essex NHS Foundation Trust, Basildon, Essex, UK; MTRC, Anglia Ruskin School of Medicine, Chelmsford, Essex, UK.
This article aims to highlight high-quality observational and intervention studies focused on promoting psychological well-being among cardiac arrest (CA) survivors and their families. Following CA, many patients experience significant psychological distress, including depression, generalized anxiety, and post-traumatic stress. Recent studies indicate that this distress can narrow patients' focus, resulting in heightened awareness of cardiac signals-such as fluctuations in heart rate or blood pressure-that lead to constant monitoring and increased anxiety.
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