Biology subjects

Gonzalez Bosc, L. V.

Publications and source records attributed to Gonzalez Bosc, L. V..

3 recordsLinked to original sources

bioRxiv2026

Hydrogen sulfide-mediated vasodilation requires heme oxygenase-derived carbon monoxide

BackgroundHydrogen sulfide (H2S) is an important endothelial-derived vasodilator, but the signaling mechanism remains incompletely understood. We previously demonstrated that H2S-mediated vasodilation requires transient receptor potential vanilloid type 4 (TRPV4) channels. Because H2S has been reported to enhance heme oxygenase (HO) activity and HO-derived carbon monoxide (CO) regulates endothelial signaling, we hypothesized that H2S-mediated vasodilation requires HO-2-derived CO. MethodsPressure myography was performed in isolated rat mesenteric arteries to determine the contribution of HO, TRPV4, eBK, and SK/IK channels to H2S-mediated vasodilation. HO-2 sulfhydration was assessed using a maleimide assay, and spatial association among HO-2 and TRPV4 was examined using proximity ligation assays in human aortic endothelial cells. ResultsH2S Selicited concentration-dependent vasodilation that was abolished by HO inhibition. Repletion of CO restored H2S-mediated vasodilation in the presence of HO inhibition. CO-mediated vasodilation was abolished by TRPV4 and SK/IK inhibition but was unaffected by eBK inhibition. H2S increased HO-2 sulfhydration and enhanced HO activity. In endothelial cells, HO-2 and TRPV4 exhibited close spatial association. ConclusionsThese findings support a model in which H2S stimulates HO-2-derived CO production, leading to TRPV4-dependent endothelial signaling, SK/IK activation, and vasodilation. Together, the data support the existence of an endothelial HO-2/TRPV4/SK/IK signaling domain that contributes to H2S-mediated vascular reactivity.

physiology↗

bioRxiv2025

Shear Stress Regulates ABCA1-dependent Membrane Cholesterol Content in Endothelial Cells Facilitating H2S-dependent Vasodilation

Endothelial cells (ECs) express an array of integral membrane proteins, including ion channels and transporters that contribute to blood flow regulation and cell-cell communication. Many of these membrane proteins are regulated by plasma membrane cholesterol content. The ATP-binding cassette family a1 (ABCA1) transporter is a regulator of membrane cholesterol content. We have shown increased ABCA1 mRNA expression and reduced EC membrane cholesterol in resistance mesenteric arteries compared to conduit arteries. Previous studies suggest shear stress (SS) can increase or decrease ABCA1 expression in a cell-type-dependent manner. HypothesisSS sustains lower EC membrane cholesterol concentration through ABCA1-mediated cholesterol transport, facilitating H2S-mediated vasodilation. MethodsThe effect of SS on ABCA1 and membrane cholesterol content was assessed in pressurized mesenteric arteries from male Sprague-Dawley rats and cultured human aortic endothelial cells. Pressure myography was used to assess the effects of ABCA1 inhibition on H2S-mediated vasodilation. Filipin was used to assess EC membrane cholesterol content. ResultsSS increased ABCA1 expression in the endothelium of mesenteric arteries and cultured human aortic endothelial cells and markedly reduced EC membrane cholesterol. Inhibition of ABCA1 increased EC membrane cholesterol content and abolished H2S-induced vasodilation. ConclusionSS facilitation of EC-dependent vasodilation appears to be mediated by membrane cholesterol content.

physiology↗

bioRxiv2025

Acid-Sensing Ion Channel 1a Deficiency Drives Endocrine Hypertension in Male Mice

BackgroundAcid-sensing ion channel 1a (ASIC1a) is an H+-gated cation channel that responds to extracellular acidosis in both normal and pathological states, including ischemia, inflammation, and metabolic disturbances. While ASIC1a regulates vascular reactivity, its role in blood pressure regulation remains unclear, particularly concerning sex, aging, and disease. This study aims to investigate whether ASIC1a: 1) contributes to cardiovascular function in a sex-dependent manner; 2) plays a dynamic role in cardiovascular homeostasis with aging; and 3) modulates the development of angiotensin II-induced systemic hypertension. MethodsRadiotelemeters were implanted in 6- and 18-month-old male and female wild-type (Asic1a+/+) and ASIC1a knockout (Asic1a-/-) mice to monitor mean arterial blood pressure and heart rate under baseline conditions and in response to angiotensin II. Blood gases, electrolytes, hormones, and end-organ injury were also assessed. ResultsAged male Asic1a-/- mice develop hypertension driven by aldosterone excess and sympathetic overactivity, which is accompanied by cardiac hypertrophy, aortic fibrosis, and glomerular hypertrophy. Female Asic1a-/- mice remain unaffected. In male Asic1a-/- mice, hyperaldosteronism occurs independent of the renin-angiotensin system and mitigates angiotensin II-induced hypertension. Furthermore, 6-month-old male Asic1a-/- mice exhibit elevated corticosterone, hypokalemia, reduced urine osmolality, increased pulse pressure, and cardiomyocyte hypertrophy that precedes hypertension. ConclusionsThese findings establish ASIC1a as a novel, sex-specific regulator of cardiovascular function, linking early corticosterone excess in male mice to hyperaldosteronism and implicating ASIC1a deficiency as a potential driver of endocrine-related hypertension. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/645371v2_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@145dcf0org.highwire.dtl.DTLVardef@1ac468eorg.highwire.dtl.DTLVardef@14c4ad5org.highwire.dtl.DTLVardef@1c4fd2e_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗