Clinical and Experimental Hypertension最新文献

Myocardial infarction (MI) is a leading cause of morbidity and mortality globally, primarily due to oxidative stress-induced cardiomyocyte apoptosis and adverse cardiac remodeling. OL-FS13, a neuroprotective peptide derived from Odorrana livida, has previously shown anti-apoptotic effects in cerebral ischemia models. However, its role in myocardial protection remains unclear. In this study, we investigated the cardioprotective effects of OL-FS13 in both in vitro and in vivo models of MI. Hydrogen peroxide (H₂O₂) was used to induce oxidative stress in primary neonatal rat cardiomyocytes, while permanent ligation of the left anterior descending (LAD) coronary artery was employed to establish a murine MI model. OL-FS13 treatment significantly attenuated cardiomyocyte apoptosis, reduced ROS accumulation, improved left ventricular function, and decreased infarct size. Mechanistically, OL-FS13 activated the Nrf2/HO-1 signaling pathway, restoring antioxidant protein levels and suppressing oxidative stress-induced apoptosis. Pharmacological inhibition of Nrf2 with ML385 abrogated the antioxidant and anti-apoptotic effects of OL-FS13 both in vitro and in vivo, confirming the central role of this pathway. These findings demonstrate that OL-FS13 exerts potent cardioprotective effects via Nrf2/HO-1 pathway activation and ROS suppression, suggesting its potential as a novel therapeutic agent for the treatment of myocardial infarction.

Background: Hypertension is thought to accelerate biological aging. However, evidence of a causal effect is lacking. This study aimed to provide evidence of a relationship between hypertension and biological aging by analyzing data from the 2005-2010 National Health and Nutrition Examination Survey (NHANES) and by Mendelian randomization (MR).

Methods: The association of hypertension with PhenoAge and PhenoAge acceleration was assessed by weighted multivariable-adjusted linear regression using the NHANES data. Two-sample MR was then performed using summary data from genome-wide association studies to determine causal associations of hypertension with accelerated DNA methylation (DNAm) and proxies of age, including telomere length, frailty index, and facial aging. Inverse variance weighting and complementary MR methods were used to confirm the causal relationship between hypertension and biological aging. The robustness of the results was confirmed by sensitivity analyses.

Results: Data for 6102 NHANES participants were analyzed. Weighted multivariable-adjusted linear regression analyses showed that hypertension increased PhenoAge (β = 12, 95% CI: 11-13, p < 0.001) and was positively associated with PhenoAge acceleration (β = 0.56, 95% CI: 0.15-0.98, p = 0.009). The MR results also suggested a potential causal association of hypertension with DNAm PhenoAge acceleration (OR 1.31, 95% CI: 1.07-1.60, p < 0.05), DNAm GrimAge acceleration (OR 1.33, 95% CI: 1.13-1.57, p < 0.05), and the frailty index (OR 1.09, 95% CI: 1.07-1.11, p < 0.05). Sensitivity analyses confirmed the robustness and reliability of these findings.

Conclusion: Hypertension increases PhenoAge and is correlated with PhenoAge acceleration. The potential causal association between hypertension and multiple biological indicators of aging provides clues to the relationship between hypertension and epigenetic aging.

Background: The high-altitude adaptation genes EPAS1 (HIF-2α) and EGLN1 (PHD2) in the HIF-PHD oxygen-sensing pathway regulate erythropoiesis and iron homeostasis and are implicated in hypoxia-related pulmonary vascular disease, yet causal roles are unclear.

Methods: This study applied a drug-target Mendelian randomization (DTMR) framework. Cis-eQTLs were used to instrument EPAS1/EGLN1 expression; gene-restricted erythroid instruments were built from genome-wide significant variants within ± 100 kb for hemoglobin (HGB), hematocrit (HCT), and red blood cell count (RBC). Primary analyses used inverse-variance weighted (IVW) and summary-data-based Mendelian randomization (SMR) with eight sensitivity approaches. Outcomes included pulmonary embolism (PE), pulmonary arterial hypertension (PAH), pulmonary-artery structural indices, and right-heart MRI traits. Two-step mediation MR evaluated iron-status traits.

Results: In SMR-DTMR, higher EPAS1 expression associated with lower PE risk (OR = 0.861; 95% CI, 0.758-0.979). In IVW-DTMR, EGLN1-mediated increases in HGB/HCT/RBC raised PE risk (HGB: OR 2.55; HCT: OR 2.45; RBC: OR 1.91) and were associated with lower systolic pulmonary artery-to-aorta ratio (PA/Ao) (HGB β-0.322; HCT β-0.282; RBC β-0.425). EPAS1-mediated HGB/HCT/RBC were associated with reduced right ventricular peak filling rate (RVP-FR; β-33.8 to -28.1). Mediation indicated serum iron partially mediated the EGLN1→(HGB/HCT)→PE pathway (3.6-3.8%), with a potential effect for RBC; ferritin potentially mediated the EPAS1→RBC→PA/Ao pathway. Multiple sensitivity analyses supported robustness.

Conclusions: EGLN1-driven erythropoietic upregulation increases PE risk and adversely affects pulmonary artery structure, whereas higher EPAS1 expression reduces PE risk. These genetic findings support targeted modulation of HIF-2α and iron metabolism.

Background: Apical muscular ventricular septal defects (mVSDs) are surgically challenging because of their location. Although transcatheter device closure is effective in many patients, large apical defects in infants present specific technical limitations and risks.

Case presentation: A 6-month-old infant (4.5 kg, 62 cm) with severe pulmonary hypertension and marked feeding and respiratory difficulties was found to have a 10 mm apical mVSD.

Intervention: The defect was closed using a 10-12 mm arterial duct occluder (PushMed, China) via a hybrid transcatheter approach.

Outcome: The procedure achieved complete defect closure without immediate complications. At 3 months' follow-up the infant demonstrated significant weight gain and clinical improvement.

Conclusions: Hybrid transcatheter closure with an arterial duct occluder can be a feasible and effective option for large apical mVSDs in select infants. Careful patient selection and close follow-up remain essential.

This prospective cohort study investigated the association between the albumin to serum creatinine ratio (sACR) and heart failure (HF) incidence in 150 chronic kidney disease (CKD) patients. Over a median 23-month follow-up, 114 HF events occurred. Multivariate Cox regression revealed a higher HF risk in the lowest versus highest sACR tertile (adjusted HR=1.742, 95% CI=1.341-2.002, p=0.023). Lower sACR correlated with worsened cardiac structure/function. The predictive AUC for HF was 0.64 for sACR alone and improved to 0.79 when combined with clinical covariates. We conclude that low sACR is independently associated with increased HF incidence in CKD patients.

Background: To evaluate the efficacy of an interdisciplinary care model with family empowerment (ICCM-FE) on clinical and psychosocial outcomes in patients with hypertension and diabetes.

Methods: This prospective randomized controlled trial (RCT) enrolled 187 patients with comorbid hypertension and diabetes from January 2023 to March 2024. Patients were randomly assigned to a control group (n = 93) receiving routine care and an intervention group (n = 94) receiving ICCM-FE intervention. Follow-up was conducted over 6 months to assess blood pressure (SBP and DBP), glucose levels (FPG and HbA1c), quality of life (SF-36 scale), psychosocial adaptation (PAIS-SR scale), and nursing satisfaction (NSNS scale) pre- and post-intervention.

Results: After 6 months, both groups exhibited significant improvements in SBP, DBP, FPG, and HbA1c (p < 0.05), with the intervention group achieving better outcomes than the control group (p < 0.05). The intervention group also demonstrated higher scores on the SF-36, General Self-Efficacy Scale (GSES), and NSNS scale, while lower scores on the PAIS-SR scale compared to the control group (p < 0.05).

Conclusion: Compared with routine care, the ICCM-FE intervention, which incorporates the COM-B model and structured family engagement, significantly improved clinical outcomes and psychosocial adaptation in patients with comorbid hypertension and diabetes. These findings highlight the model's effectiveness in promoting better health behavior, emotional coping, and care satisfaction, supporting its potential for broader clinical application.

Objective: The concurrent prevalence of major depression and hypertension represents a significant clinical concern. This study aims to investigate the potential causal relationship among these conditions from a genetic standpoint.

Methods: The genome-wide association studies (GWAS) summary data for major depression were obtained from the IEU OpenGWAS database. Concurrently, GWAS summary data for hypertension were sourced from the Finnish consortium. All the participants have European ancestry. A two-sample bidirectional Mendelian randomization (MR) study was conducted to examine the relationship between major depression and hypertension. To ensure the reliability of the results, several sensitivity analyses were performed, addressing heterogeneity, horizontal pleiotropy, outliers, the influence of individual single nucleotide polymorphisms (SNPs), and adherence to normal distribution assumptions.

Results: The findings revealed a significant positive genetic causal association between major depression and hypertension (P = 0.016, odds ratio [OR] = 1.160, 95% confidence interval [CI] = 1.029-1.308). Conversely, no genetic causal relationship was identified between hypertension and major depression (P = 0.670, OR = 1.004, 95% CI = 0.985-1.024). Our MR analysis indicated the absence of heterogeneity and horizontal pleiotropy, with no detected outliers. Additionally, the analysis was not influenced by any SNP and demonstrated a normal distribution.

Conclusion: The results of this study indicate that severe depression is a risk factor for hypertension of European ancestry. The conclusion of this study should be used with caution when applied to other populations. Clinically depressed patients should be closely monitored for the onset of hypertension.

Background: Psychological problems such as anxiety and depression in children show an increasing prevalence, but low treatment rates and few interventions have been implemented. The relationship between combined exercise and psychological interventions on anxiety, depression, and blood pressure in children has not been clearly studied. The aim of this study was to investigate the effects of a combined psychological and exercise intervention program on children's anxiety and depression conditions and blood pressure.

Methods: Thirty-nine children aged 8-15 years from a middle school in Xishui County were included in a randomized controlled trial (18 in the intervention group and 21 in the control group). Physical examinations, such as blood pressure and questionnaires on anxiety/depression and quality of life, were collected. The intervention group underwent 7 days of continuous comprehensive motor‒psychological intervention.

Results: The Self-rating Anxiety Scale(SAS) in the intervention group decreased by 11.47 ± 7.99, which is higher than the control group decreased by 5.00 ± 10.22. The difference was statistically significant (P < 0.05). The self-rated depression scale (SDS) of the intervention group decreased from 58.80 ± 6.97 to 51.73 ± 5.76, with a statistically significant difference (P <0.05).The intervention activities also had a significant effect on the children's QoL indicators of companionship, living convenience, and living environment factor (all p ≤ 0.05). The intervention activities decreased the blood pressure and BMI of the children with statistically significant differences (p < 0.05).

Conclusion: The comprehensive intervention combining exercise and psychology domonstrated an effective approach to improve anxiety-depression status and blood pressure in adolescents and children, with a positive impact on quality of life.

Background: Transcatheter adrenal artery embolization (TAAE) has emerged as a minimally invasive technique for selective adrenal ablation, offering potential therapeutic applications for various adrenal disorders. However, its safety profile remains insufficiently characterized. This preclinical study aimed to evaluate the physiological, biochemical, and histological effects of ethanol-based TAAE in a large-animal model.

Methods: Twelve Bama miniature pigs were randomized into embolization (n = 6) and sham (n = 6) groups. The embolization group underwent selective unilateral adrenal artery embolization with absolute ethanol, while the sham group received catheterization without ethanol injection. Hemodynamic parameters, plasma adrenal hormones, renal function, and cardiac function were assessed preoperatively, intraoperatively, and at 4 weeks post-procedure. Histological analysis of adrenal tissues was performed to evaluate ablation effects.

Results: TAAE induced a transient but significant rise in systolic blood pressure (from 128 ± 11 to 219 ± 13 mmHg, P < 0.01) and plasma norepinephrine levels (from 7.4 ± 0.8 to 1199 ± 247 nmol/dL, P < 0.01) during ethanol injection, which normalized by 4 weeks. No significant differences were observed in body weight, renal function, serum electrolytes, adrenal hormone levels, or echocardiographic parameters at follow-up. Histological analysis revealed localized adrenal cortical necrosis, architectural disruption, and increased interstitial fibrosis in the embolization group (P < 0.01), without evidence of systemic toxicity or off-target embolization.

Conclusion: TAAE is a feasible and well-tolerated method for targeted adrenal ablation in a porcine model. This study provides foundational preclinical evidence supporting further investigation of TAAE as a minimally invasive, organ-sparing approach for the treatment of diverse adrenal pathologies.

This study was designed to elucidate the role of circPcmtd1 in regulating pulmonary artery smooth muscle cells (PASMCs) proliferation and migration, through the HSP90AB1/AKT signaling axis, in rats with high pulmonary blood flow-induced PAH. A rat model of high pulmonary blood flow-induced PAH was established by an abdominal aorta-inferior vena cava shunt surgery. The expression of circPcmtd1 in PASMCs of rats with high pulmonary blood flow-induced PAH was verified by qRT-PCR. The effects of circPcmtd1 on the proliferation and migration of PASMCs were explored by lentiviral transfection, cell proliferation assay, and scratch assay. RNA pull-down assay, mass spectrometric analysis, lentiviral transfection, and western blot were used to explore the molecular mechanisms by which circPcmtd1 regulated the proliferation and migration of PASMCs in rats with high pulmonary blood flow-induced PAH. We found that the expression of circPcmtd1 was down-regulated in PASMCs of rats with high pulmonary blood flow-induced PAH. Functional experiments showed that overexpression of circPcmtd1 inhibited the proliferation and migration of PASMCs. RNA pull-down assay and mass spectrometric analysis revealed that circPcmtd1 could bind to HSP90AB1 protein. Further, we found that high expression of HSP90AB1 could promote the proliferation and migration of PASMCs in rats with high pulmonary blood flow-induced PAH. Mechanistic investigation demonstrated that the binding of circPcmtd1 to HSP90AB1 could regulate the phosphorylation of AKT. In conclusion, circPcmtd1 directly bound to the HSP90AB1 protein to mediate the phosphorylation of AKT, thereby regulating the proliferation and migration of PASMCs.