Gut microbiota-derived metabolites, including trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), are associated with vascular function and blood pressure (BP) regulation. However, whether high-intensity interval training (HIIT) is accompanied by coordinated changes in these metabolites, along with improvements in ambulatory BP (ABP), and arterial stiffness in adults with hypertension (HTN), remains unclear. In this 12-week randomized controlled trial (RCT), 60 adults with HTN (age 60.1 ± 6.1 years) were allocated to the HIIT or CONTROL group. HIIT consisted of 10-15 cycling intervals (1 min at 85-90% of heart rate reserve) interspersed with 1 min of active recovery (50-55% of heart rate reserve), performed three times per week. 24 h ABP, carotid-femoral pulse wave velocity (cfPWV), and plasma concentrations of TMAO and SCFAs were assessed before and after intervention. Compared with CONTROL, HIIT was associated with greater reductions in office BP (6.9/3.1 mmHg, P < 0.001), 24 h systolic and diastolic ABP (6.1/3.5 mmHg, P < 0.001) and cfPWV (225.7 ± 41.8 cm/s, P < 0.001). Plasma TMAO concentrations decreased following HIIT (1.41 ± 0.66 μmol/l, P = 0.001), while acetate (5.72 ± 2.27 μmol/l), propionate (0.76 ± 0.36 μmol/l), and butyrate (0.65 ± 0.21 μmol/l) increased ( Ps = 0.001). Reductions in systolic ABP ( r = 0.780, P < 0.001), diastolic ABP ( r = 0.713, P < 0.001), and cfPWV ( r = 0.542, P = 0.002) were positively associated with decreases in TMAO and inversely associated with changes in SCFAs levels. In adults with HTN, HIIT was associated with improvements in ABP, arterial stiffness, and gut microbiota-derived metabolites level. These findings support an integrated relationship between exercise-related metabolic adaptation and vascular function, highlighting the potential relevance of the gut-vascular axis in BP regulation.

Night shift work (NSW) is associated with increased cardiovascular risk, but its impact on vascular function and the role of lifestyle factors in healthy individuals remain unclear. We aimed to compare vascular function between NSW and day workers (DW) and to examine associations with objectively measured lifestyle behaviors. In this cross-sectional study, 40 healthy adults (20 DW, 20 NSW) underwent assessments of flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI). Physical activity and sleep status were objectively measured using triaxial accelerometry for 7 consecutive days. Group comparisons and correlation analyses were conducted to evaluate the effects of NSW and its association with lifestyle factors. FMD was significantly lower in the NSW group than in the DW group (4.0% vs. 7.0%, P < 0.01), while baPWV and ABI showed no between-group differences. In the overall cohort, FMD was positively correlated with time in bed, total sleep time, and sleep efficiency, and negatively correlated with nocturnal awakening. Subgroup analysis revealed that FMD was associated with sleep quality in DW and with physical activity patterns in NSW. Chronic night shift work is associated with impaired endothelial function in healthy adults, potentially driven by disrupted sleep and reduced physical activity. Early assessment using FMD and targeted behavioral interventions may help preserve vascular health among shift workers. This study shows that healthy adults who regularly work night shifts have poorer blood vessel function than people who only work daytime hours, and that sleep and physical activity patterns may help explain this difference.

Chikusetsusaponin V improves vascular endothelial dysfunction by binding to ITGB1 and mediating PURA-eNOS activation in mice with diabetes mellitus.

ObjectiveTo evaluate the clinical outcomes and safety of a triple percutaneous treatment protocol involving mechanical thrombolysis, direct thromboaspiration, and low-dose tPA thrombolysis in patients with moderate to high or high-risk pulmonary embolism (PE).DesignSingle-center retrospective cohort study.MethodsWe included patients aged 18years or older with moderate to high or high-risk PE, as determined by a chest vascular scan. The primary outcome was survival. Secondary outcomes included functional capacity (FC), systolic pulmonary artery pressure (sPAP), right ventricle (RV) dilation, and tricuspid annular plane systolic excursion (TAPSE). All outcomes were assessed at 48-h post-procedure and at the 6-month follow-up. Additionally, the incidence of adverse events was evaluated during the 48-h following the procedure.ResultsThirty-five patients were included, comprising 51.43% males, with a mean age of 55years (SD 18). Survival at 48-h post-procedure was 97%. Of the 19 patients who followed up for 6months, 95% survived. Eight patients (23%) had FC I-II at admission, which increased to 91% at 48-h post-procedure and 100% at 6months of follow-up. At admission, 25 patients (71%) had moderate to severe RV dilation. In contrast, 33 patients (94%) had a normal or slightly dilated RV at 48-h post-procedure, and 100% (n/N 19/19) at 6months of follow-up. In addition, there was a significant reduction in mean baseline sPAP to 36mmHg (SD 10.3) at 48-h post-procedure and to 29mmHg (SD 4.9) at 6-month follow-up (P < .001). TAPSE increased significantly to 20.8mm (SD 4.8) at 48-h post-procedure and to 22.3mm (SD 2.8) at 6-month follow-up (P < .001). No adverse events occurred.ConclusionIn patients with moderate to high or high-risk PE, the triple percutaneous treatment protocol appears to be an effective and safe intervention. This strategy achieves high survival and adequate FC, normalizing pulmonary vascular pressures and RV function.

Role of alpha-terpineol modulating pathway nitric oxide into coronary tissues: A confluent mechanism for the cardioprotection?

Kisspeptin-54 confers renal protection in diabetic nephropathy by ameliorating endothelial permeability through ZEB1 inhibition.

Interpreting central hemodynamics in durable biventricular circulatory support patients.

Sweroside ameliorates endothelial dysfunction via the KLF2-mediated repression of the FABP4/CCL20 signaling axis.

Skeletal muscle-derived Metrnl induced by exercise displays the roles of endothelioprotective and anti-atherosclerosis in male mice through KIT/NFκB signaling.

Feasibility and acceptability of remote ischemic conditioning combined with low-intensity resistance training in older adults with mobility impairments: A randomized controlled pilot trial protocol.

Pinto bean supplementation prevents vascular dysfunction by modulating the gut microbiome in an interleukin-10-dependent manner in mice fed an atherogenic diet.

Loss of erythrocyte arginase-1 impairs vasorelaxation due to endothelial GSNOR overexpression and denitrosylation of G protein subunits.

Obesity is a chronic, progressive, relapsing and treatable multifactorial, neurobehavioral disease and leads to adverse effects on health. The leading basis of obesity is long term energy inequality between consumed calories and expended calories. Excess adiposity contributes to alterations in vascular function and blood pressure regulation, increasing the likelihood of developing hypertension. The objective of this study was to assess the blood pressure and glycated hemoglobin in obese and non-obese male. This cross-sectional type of observational study was carried out in the Department of Physiology in co-operation with the outpatient Department of Medicine units of Mymensingh Medical College Hospital, Mymensingh to assess the blood pressure and glycated hemoglobin in obese and non-obese male from January 2024 to December 2024. A total number of 200 male subjects were included in this study among them 100 were adult obese male and 100 were healthy non obese males. The data was analyzed using SPSS software, version 29.0. To see the significant differences between groups, we used the unpaired Students 't' test and shared results as mean ±SD. Laboratory analysis of serum glycated hemoglobin was done. The mean±SD of glycated hemoglobin of adult non obese group and adult obese group were 5.44±0.579 and 6.64±0.505% respectively. In adult obese group, glycated hemoglobin was increased in comparison to non obese adult group. In this study, glycated hemoglobin was statistically highly significant (p<0.001) in study group in comparison to control group. Routine monitoring of glycated hemoglobin is recommended to prevent obesity related complications to promote healthy life.

L-type CaV1.2 channels are key regulators of cellular function in diverse cell types, controlling processes that range from gene expression to muscle contraction. In arterial myocytes, CaV1.2 channels traffic to the plasma membrane and assemble into clusters that control Ca2+ influx. Changes in the size and number of these CaV1.2 clusters have been linked to altered channel and vascular function in diabetic hyperglycaemia, angiotensin II (AngII) signalling and hypertension. Yet, the dynamics governing the distribution of vascular CaV1.2 at the plasma membrane remain poorly understood. Here, we found that microtubule-mediated transport actively shapes CaV1.2 distribution under hyperglycaemia and AngII signalling. Employing high-resolution imaging, we tracked live CaV1.2 trafficking in male arterial myocytes using a dual approach: unpassaged cells expressing vascular CaV1.2-and freshly isolated cells from a CaV1.2-mClover2 knock-in mouse, which enabled endogenous channel visualization in native tissue. By recreating diabetic hyperglycaemia (20mM d-glucose) and enhancing AngII signalling in vitro, we uncovered distinct CaV1.2 trafficking patterns in both cultured and freshly isolated arterial myocytes that were dependent on an intact microtubular network. Importantly, microtubule disruption abolished CaV1.2 dynamics and prevented AngII-induced calcium elevations in both isolated myocytes and intact arteries. These findings identify microtubule-dependent CaV1.2 trafficking as a key mechanism by which hyperglycaemia and AngII signalling may drive channel reorganization and calcium dysregulation. The results have implications for vascular dysfunction in diabetes and hypertension, and open new potential therapeutic avenues targeting the cellular transport machinery. Moreover, the CaV1.2-mClover2mouse provides a useful tool for investigating native channel behaviour in living tissues across physiological and pathological contexts. KEY POINTS: Live-cell total internal reflection fluorescence and spinning-disk confocal imaging revealed that vascular CaV1.2 channels exhibit distinct perimembrane behaviours in male arterial myocytes, including kiss-and-stay, kiss-and-run, and homotypic fusion and fission events. Microtubules are essential for vascular CaV1.2 structural dynamics, with nocodazole-induced microtubule disruption significantly reducing channel mobility, speed and displacement. Hyperglycaemic or angiotensin II-stimulated environments rapidly increased vascular CaV1.2 clustering at the plasma membrane, and microtubule disruption abolished these pathological elevations in clustering and intracellular Ca2+ in both isolated myocytes and intact arteries. A CRISPR/Cas9-generated CaV1.2-mClover2 knock-in mouse enabled endogenous channel visualization in native tissue, providing a transformative tool for investigating CaV1.2 behaviour in physiological and pathological contexts.

Dietary organosulfur compounds and the H2S-polysulfide redox axis: Current evidence and limitations.

Metabolic dysfunction-associated steatotic liver disease (MASLD) increases cardiovascular and kidney disease risk. Insulin-like growth factor 1 (IGF-1) regulates metabolic and vascular function, but its role in long-term cardio-kidney outcomes (CKO) in MASLD remains unclear. This study examined the association between MASLD, IGF-1 levels and CKO. In this prospective cohort study, we used data from 214 512 UK Biobank participants without baseline cardiovascular or chronic kidney disease (CKD). Participants were categorized into four groups: no-MASLD and MASLD stratified by age- and sex-specific tertiles of serum IGF-1 (T1-T3). The primary outcome was a composite CKO; secondary outcomes were incident CKD and 3-point major adverse cardiovascular events (3P-MACE). Over a median 13-year follow-up, 20 395 CKOs occurred. MASLD increased event rates across all IGF-1 tertiles (p < 0.001), with a significant interaction observed between MASLD and IGF-1 levels (P for interaction = 0.014). In multivariable Cox models, MASLD remained independently associated with CKO risk, strongest in the lowest IGF-1 tertile (T1: adjusted hazards ratio [aHR], 1.24 [95% CI: 1.18-1.30] vs. no-MASLD). Similar trends were observed for incident CKD (T1: aHR, 1.35 [95% CI: 1.22-1.49]) and 3P-MACE (T1: aHR, 1.26 [95% CI: 1.18-1.35]). Subgroup analyses indicated consistent associations across sex, BMI and diabetes, with stronger effects in participants < 65 years and markedly greater CKD risk among those with baseline albuminuria. MASLD independently predicted CKO, particularly among individuals with low IGF-1 levels. Incorporating IGF-1 into clinical evaluations may improve risk stratification beyond conventional metabolic factors.

Targeted endothelial GTPCH1/BH4 pathway activation reverses vascular dysfunction in smoking-associated obesity.

Supervised In-Person versus Home-Based Exercise in Peripheral Artery Disease: A Pilot Comparative Study.

Cellular senescence-an age-associated state characterized by irreversible cell cycle arrest and proinflammatory signaling-contributes to vascular dysfunction and cardiovascular disease. However, the molecular mechanisms linking senescence to vascular impairment remain incompletely defined. Progranulin (PGRN) is a multifunctional protein involved in inflammation, lysosomal function, and cellular homeostasis, but its role in vascular aging is not well understood. We assessed PGRN expression in human and mouse arteries and in senescent vascular smooth muscle cells (VSMCs). Vascular function was examined in PGRN-deficient (PGRN-/-) mice. Cellular senescence was pharmacologically targeted using the senolytic agents navitoclax (ABT-263) and fisetin, and vascular phenotypes were evaluated in adult (6-mo-old) and aged (18-mo-old) mice. PGRN expression increased with age in human and mouse arteries and strongly correlated with p21 expression. In adult mice, PGRN deficiency induced endothelial dysfunction, enhanced vasoconstriction, and promoted vascular inflammation and remodeling. Transcriptomic profiling of PGRN-/- VSMCs revealed a senescence-associated signature characterized by impaired oxidative phosphorylation, epigenetic dysregulation, and enrichment of collagen-related pathways. Senolytic treatment improved endothelial-dependent relaxation but increased vascular contractility in PGRN-/- mice. In aged mice, PGRN deficiency exacerbated vascular dysfunction, remodeling, and renal injury without further increases in senescence markers, consistent with premature rather than progressive vascular senescence. PGRN deficiency promotes premature vascular dysfunction through coordinated mitochondrial, epigenetic, inflammatory, and structural mechanisms. These findings identify PGRN as a key modulator of vascular homeostasis and suggest that impaired PGRN signaling may predispose to early-onset vascular and cardiorenal dysfunction.NEW & NOTEWORTHY This study identifies progranulin (PGRN) as a key regulator of premature vascular dysfunction. Using human and mouse arteries and integrated multi-omics analyses, we show that PGRN deficiency induces early vascular senescence, mitochondrial dysfunction, epigenetic remodeling, and fibrosis. Senolytic treatment uncovers divergent roles of endothelial versus smooth muscle cell senescence in vascular function, highlighting PGRN as an important modulator of vascular homeostasis during aging.

Endothelial dysfunction is a risk factor for lipid metabolism disorders: underlying mechanisms and potential treatments.