This review evaluates the antihypertensive potential of next-generation incretin-based therapies, including GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists. It examines their effects on blood pressure reduction, underlying mechanisms, clinical benefits, and implications for future guidelines.

Recent large-scale trials demonstrate that incretin-based therapies such as semaglutide and tirzepatide significantly reduce body weight, blood pressure, and cardiovascular outcomes. Mediation analyses indicate that weight loss explains a substantial proportion of blood pressure reduction, while direct effects on vascular function, renal sodium handling, and neurohumoral pathways also contribute. These effects are consistent across diverse populations, including individuals without overt hypertension. Incretin-based therapies represent a promising approach in hypertension management, combining metabolic and cardiovascular benefits. Despite the lack of trials with blood pressure as a primary endpoint, current evidence supports their use in selected high-risk populations and suggests an emerging role in future guideline recommendations.

The special AT-rich sequence-binding protein 2 (SATB2) is associated with human cognitive ability. Mutations in the SATB2 gene lead to SATB2-associated syndrome (SAS), characterized by severe intellectual disability. SATB2 is mainly expressed in pyramidal neurons in the cerebral cortex and hippocampus, playing a crucial role in cognitive processes. However, the function of SATB2 in the adult hippocampus remains unclear. In this study, we deleted Satb2 in the CA1 region of the adult mouse hippocampus and observed cognitive impairments along with significant changes in soma and dendrite morphology. Additionally, we identified the growth factor pleiotrophin (PTN) as a downstream target of Satb2, essential for mediating its impact on cognitive functions. Importantly, increasing PTN expression mitigated the morphological and behavioral deficits resulting from Satb2 deletion in CA1. Our findings highlight the importance of hippocampal Satb2 in regulating cognitive function in adult mice through PTN modulation.

Ischemic stroke remains a leading cause of death and long-term disability worldwide, and effective neuroprotective therapies applicable to a broad patient population are still limited. Although mesenchymal stromal cell-derived exosomes (MSC-EXO) have emerged as promising cell-free therapeutic agents, evidence regarding exosomes derived from human amnion-derived mesenchymal stromal cells (AMSC-EXO) in cerebral ischemia remains scarce.

Human AMSC-EXO were isolated from conditioned media of cultured human amnion-derived mesenchymal stromal cells and characterized by nanoparticle tracking analysis and exosomal marker expression. Male mice were subjected to middle cerebral artery occlusion and randomly assigned to receive intravenous AMSC-EXO or vehicle 24 h after ischemia. Neurological function, motor coordination, and spatial working memory were assessed at 3 and 14 days. Post-ischemic neuroinflammation, neuronal degeneration, and endothelial cell proliferation were evaluated by immunohistochemistry and enzyme-linked immunosorbent assay in a blinded manner.

Systemic administration of AMSC-EXO significantly improved neurological outcomes and motor performance after cerebral ischemia and enhanced spatial working memory. AMSC-EXO treatment markedly suppressed microglial activation and reduced the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6, in the ischemic brain. In addition, neuronal degeneration in the cortical infarct border zone was significantly attenuated. At later stages, AMSC-EXO significantly increased the number of proliferating endothelial cells, suggesting a potential involvement in neurovascular remodeling.

Human AMSC-derived exosomes exert neuroprotective and neurovascular restorative effects after cerebral ischemia by suppressing post-ischemic neuroinflammation, reducing neuronal cell death, and promoting endothelial cell proliferation. AMSC-EXO represents a promising, scalable, and cell-free therapeutic strategy for ischemic stroke.

Ultra-processed foods (UPFs) have increasingly displaced traditional diets globally and have become a significant public health concern, particularly in relation to cardiovascular (CV) diseases. UPFs are defined as food products primarily composed of cheap industrial ingredients, additives, and neo-formed compounds, often with little to no nutritional value. These foods are highly processed and contain additives that can have harmful effects on health. While traditional dietary guidelines have long emphasized the importance of limiting animal-derived fats and promoting the intake of fruits, vegetables, and unsaturated fats, recent evidence suggests that the extent and nature of food processing are also key factors in the relationship between diet and health. Studies over the past decade have highlighted that the consumption of UPFs is associated with increased CV risk, often independent of the overall diet quality. Despite growing evidence linking UPF consumption to major CV risk factors (e.g. hypertension, dyslipidaemia, obesity) and adverse CV outcomes, the role of food processing in CV health remains underrecognized in cardiology. Current dietary counselling in clinical practice tends to overlook the potential adverse impact of UPFs, with patients not receiving comprehensive nutritional guidance. This European Society of Cardiology (ESC) clinical consensus statement, developed by a multidisciplinary group of European experts, is conceived to increase awareness among clinicians about the CV risks associated with UPFs. Starting from a comprehensive review of current evidence, it provides practical, actionable advice to help the general cardiologists incorporate UPF-related assessment and counselling into their routine care. The statement also proposes a stepwise framework focused on CV prevention, including tools designed to enhance patient communication and engagement. Moreover, it discusses these clinical advices within wider strategic and policy frameworks, therefore supporting a more integrated, food-centred approach to improve CV health.

Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been implicated in cardiometabolic inflammation; however, the intracellular signaling mechanisms linking TMAO to macrophage polarization remain incompletely defined. This study aimed to investigate whether TMAO promotes macrophage M1 polarization through a Piezo1-Yes-associated protein (YAP) signaling axis. Gain- and loss-of-function approaches were performed in RAW264.7 cells and primary bone marrow-derived macrophages, including Piezo1 overexpression, small interfering RNA-mediated knockdown of Piezo1 or YAP, and pharmacological inhibition of YAP. Macrophage polarization markers were evaluated by immunofluorescence, flow cytometry, real-time quantitative polymerase chain reaction, and Western blot analysis. Intracellular Ca²⁺ levels were assessed using Fluo-4 acetoxymethyl ester fluorescence imaging. TMAO increased inducible nitric oxide synthase expression and reduced arginase-1 levels (P < .01), accompanied by elevated IL-1β and IL-6 and decreased IL-4 and IL-10 (P < .01). Piezo1 overexpression promoted M1 polarization (P < .01), whereas Piezo1 knockdown under TMAO exposure attenuated inflammatory cytokine induction (P < .001). TMAO enhanced intracellular Ca²⁺ influx (P < .001) and reduced inhibitory phosphorylation of YAP (Ser127) (P < .01). Inhibition or silencing of YAP mitigated TMAO-induced M1 marker expression and downstream kappa B/extracellular signal-regulated kinase activation (P < .05). Similar results were confirmed in primary bone marrow-derived macrophages. These findings suggest that TMAO promotes macrophage M1 polarization in association with Piezo1-dependent Ca²⁺ influx and YAP activation, identifying the Piezo1-YAP axis as a potential mechanistic interface linking microbiota-derived metabolites to inflammatory remodeling. SIGNIFICANCE STATEMENT: This study identifies the Piezo1-Yes-associated protein signaling axis as a potential drug target in trimethylamine N-oxide-induced macrophage polarization toward a proinflammatory phenotype. Inhibition of this pathway attenuates inflammatory responses, suggesting a potential pharmacological strategy for microbiota-associated cardiovascular diseases.

Myocardial infarction (MI) is the most severe clinical complication of coronary atherosclerotic heart disease (CHD), representing a leading cause of global morbidity and mortality. Qi-Blood Harmony Formula (QBHF), a traditional Chinese medicine, has shown clinical promise for managing MI; however, its underlying mechanisms remain to be fully elucidated.

This study aimed to explore the therapeutic mechanism of QBHF against MI in the context of CHD, with a specific focus on its role in angiogenesis.

QBHF chemical components were characterized by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Therapeutic efficacy was evaluated in a high-fat diet-fed ApoE^-/- mouse model with left anterior descending coronary artery ligation and in a hypoxia-induced endothelial cell model. Cardiac function and angiogenesis were assessed through histological, functional, and molecular assays, with the underlying mechanisms further investigated using bioinformatics and experimental validation.

Chemical profiling identified 67 compounds in QBHF, with eight major constituents quantified. In atherosclerosis-myocardial infarction (AS-MI) mice, QBHF dose-dependently improved cardiac function, attenuated myocardial injury, and upregulated angiogenic markers. In vitro, QBHF enhanced hypoxia-induced proliferation, migration, and tube formation in EA.hy926 cells. Mechanistically, a specific circular RNA (hsa_circ_0003296) was found to be significantly upregulated in the peripheral blood of AS and MI patients. It directly bound to eukaryotic initiation factor 4A-III (EIF4A3) to promote its ubiquitin-mediated degradation. QBHF suppressed hsa_circ_0003296 expression, thereby preventing EIF4A3 degradation. The stabilized EIF4A3 subsequently prolonged the mRNA half-lives of vascular endothelial growth factor A (VEGFA) and VEGF receptor 2 (VEGFR2), thereby promoting angiogenesis.

These results suggest that QBHF ameliorates MI in CHD by reversing hsa_circ_0003296-mediated inhibition of angiogenesis. This process is executed through the stabilization of EIF4A3, which enhances the mRNA stability of VEGFA and VEGFR2.

Adverse metabolic profile manifested as metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity affect the development and prognosis of heart failure (HF).

Whether treatments targeting metabolic derangements such as sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) are associated with improved outcomes patients with both HF and MASLD or obesity warrants investigation.

This retrospective study included 7 propensity score matched cohort analyses using deidentified electronic health record data from the TriNetX global health research network.

We evaluated the associations between MASLD, obesity, and the use of SGLT2 inhibitors or GLP-1 receptor agonists with adverse outcomes in patients with HF. Cohorts were defined based on combinations of comorbidities (HF subtype, MASLD, obesity, diabetes status) and medication exposure. Time-to-event outcomes with the Kaplain-Meier method and with Cox proportional hazards models for the calculation of hazard ratios (HRs) and 95% confidence intervals.

Among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction, MASLD was consistently linked to increased risk of nonfatal cardiovascular events, including HF (HR = 1.09, P < 0.001 and HR = 1.23, P < 0.001), myocardial infarction (HR = 1.03, P = 0.07 and HR = 1.08, P < 0.001), and stroke (HR = 1.04, P = 0.08 and HR = 1.07, P = 0.07). Use of SGLT2 inhibitors in HFpEF and MASLD patients with or without diabetes was associated with reduced all-cause mortality (HR = 0.76, P < 0.001 and HR = 0.69, P < 0.001) and major cardiovascular events. GLP-1 receptor agonists demonstrated a significant survival benefit (HR = 0.38, P < 0.001) in obese patients with HFpEF and MASLD without diabetes.

In patients with HFpEF, pharmacologic interventions targeting metabolic pathways demonstrate meaningful cardioprotective effects, especially in metabolically vulnerable subgroups.

Post-kidney transplantation hypertension is common and is frequently driven by calcineurin inhibitor (CNI)-mediated sodium retention and vasoconstriction, producing a salt-sensitive phenotype in which sodium-chloride cotransporter (NCC) inhibition remains the mechanistically aligned cornerstone of therapy. This opinion piece examines aldosterone synthase inhibitors (ASIs) as an emerging drug class that may have adjunctive relevance in selected resistant phenotypes after kidney transplantation. We summarize the class rationale, distinguish older less selective compounds from newer CYP11B2-selective agents, and position baxdrostat within the broader ASI landscape alongside lorundrostat, vicadrostat, and earlier-stage dexfadrostat data. In non-transplant populations, baxdrostat and lorundrostat have lowered blood pressure in uncontrolled or resistant hypertension, whereas vicadrostat has shown cardiorenal promise in chronic kidney disease, including combination development with empagliflozin. However, no ASI has been studied in kidney transplant recipients. This gap is especially important because transplant recipients have reduced nephron reserve, frequent CNI exposure, narrow potassium margins, and a hypertensive phenotype often dominated by NCC activation rather than uniform aldosterone excess. Accordingly, ASIs should be viewed in transplantation as hypothesis-generating investigational agents rather than therapeutic recommendations. Any transplant-specific trial should incorporate rigorous hyperkalemia monitoring, comparator arms that reflect optimized NCC-directed therapy, and formal assessment of drug-drug interactions with immunosuppressants.

Houseless trauma patients (HTPs) face triple the complications and nearly double the mortality of nonhouseless trauma patients (nHTPs), which may be related to a higher burden of undiagnosed or untreated chronic conditions. This study aims to explore whether HTPs have a longer length of stay (LOS) and encounter more difficulties in accessing rehabilitation services compared to nHTPs. We hypothesize that HTPs, as compared to nHTPs, have longer LOS and decreased access to rehabilitation services.

The 2021-2023 Trauma Quality Improvement Program database was queried for admitted adult HTPs. HTPs were compared to nHTPs. The LOS for surviving HTPs and nHTPs was compared in a variety of clinical scenarios. Chi-square and Mann-Whitney U tests were performed. A multivariable logistic regression analysis was used to determine risk of prolonged LOS (defined as ≥5 d).

From 2,474,565 patients, 26,349 (1.1%) were HTPs. HTPs exhibited higher rates of alcohol use (22.6% versus 7.4%, P< 0.001) and mental health disorders (25.1% versus 12.3%, P< 0.001). After adjusting for age, injury severity, and comorbidities, HTPs continued to have a higher risk for prolonged LOS (odds ratio 1.49, 95% confidence interval 1.44-1.54, P< 0.001). HTPs had a longer median LOS in all scenarios, most notably with severe lower extremity fractures (19 versus 10 d, P< 0.001) and severe trauma (injury severity score >15) (12 versus 8 d, P< 0.001). HTPs also had decreased discharges to short-term/intermediate/long-term care rehabilitation (6% versus 13.2%, P< 0.001) but increased rates of leaving against medical advice (10.7% vs. 1.8%, P< 0.001).

This prognostic and epidemiological analyses highlight significant disparities faced by HTPs, including longer LOS and lower rates of discharge to rehabilitation services. By focusing on integrated care models and advocating for policies that address houselessness and health disparities, hopefully we can move closer to a health-care system that serves all individuals with equity and compassion.

Older adults are disproportionately affected by suicide, yet suicidal ideation in this population remains underexplored. This study examines gender-specific risk factors and regional differences in late-life suicidal ideation across Nordic and Visegrad countries, with loneliness as a key social determinant. This study analysed data from 11,712 participants aged 50 years and older from seven European countries (Nordic and Visegrad regions), drawing on Wave 8 of the Survey of Health, Ageing and Retirement in Europe (SHARE). Logistic regression was used to examine gender- and region-specific associations with late-life suicidal ideation. Increased loneliness was strongly associated with higher odds of suicidal thoughts in both men and women. Higher education acts as a protective factor, with middle and high education reducing risk in men, and high education reducing risk in women. Living with a partner lowers suicidal thoughts for women but not for men. Age showed no consistent association, and Nordic men show a lower risk compared to their Visegrad counterparts, whereas no regional differences observed for women. Social and contextual factors, especially loneliness, education, and partnership, shape late-life suicidal ideation in gender- and region-specific ways, highlighting the need for targeted preventive interventions.