Clinical and Experimental Hypertension最新文献

Background: Non-dipper hypertension, defined by reduced nocturnal blood pressure (BP) decline, increases cardiovascular risk. Calcium-phosphate metabolism (parathyroid hormone [PTH], vitamin D [25(OH)D]) may influence circadian BP rhythms, but their independent roles remain unclear.

Objective: To investigate associations between PTH, 25(OH)D, and nocturnal BP dipping in primary hypertension, addressing prior inconsistencies.

Methods: This retrospective cohort included 585 hypertensive adults stratified by nocturnal systolic BP dipping (dippers [≥10% decline, n = 250]; non-dippers [<10%, n = 335]) using 24-hour ambulatory monitoring. Serum PTH, 25(OH)D, renal/metabolic parameters, and vascular indices were analyzed. Multivariate linear regression assessed associations with dipping, adjusted for age, sex, renal function, and arterial stiffness.

Results: Non-dippers showed elevated PTH (median: 5.23 vs. 4.70 pmol/L, p = .011) and lower 25(OH)D (30.89 vs. 36.79 nmol/L, p < .001). Adjusted models confirmed PTH (β=-0.21, 95% CI:-0.34--0.08; p = .002) and 25(OH)D (β = 0.03, 95% CI:0.01-0.04; p < .001) as associated factors of dipping. Although statistically significant, these correlations were modest and suggested possible trends rather than strong causal relationships. Age/sex effects on BP patterns became nonsignificant after adjusting for calcium-phosphate markers.

Conclusion: Calcium-phosphate dysregulation (elevated PTH, low vitamin D) independently contributes to non-dipping, suggesting biomarker-guided approaches for circadian BP control. Demographic disparities in dipping may reflect underlying mineral metabolism disturbances. Prospective trials should explore calcium-modulating therapies (e.g. vitamin D supplementation) in non-dipper hypertension.

Hypertension is one of the major risk factors for cardiovascular diseases and end-organ damage worldwide. Traditionally, it has been linked to factors such as genetics, diet, and lifestyle. However, increasing research indicates that the immune system also plays an important role in the initiation and progression of hypertension. In the initiation phase, pro-hypertensive stimuli including chronic sympathetic nervous system (SNS), high salt intake and imbalanced gut microbes all influence the function of immune cells, contributing to the development of elevated blood pressure. As hypertension progresses, many immune cells, such as macrophages, dendritic cells, NK cells, B and T lymphocytes, accumulate in organs such as the heart, blood vessels, and kidneys. These cells release effector cytokines and reactive oxygen species, exacerbating tissue damage and organ dysfunction. Meanwhile, numerous studies suggest that intervening in immune inflammatory processes has the potential to regulate blood pressure and prevent damage to vital organs. This review aims to explore the role of immune regulation in various stages of hypertension and the progress of research on immune interventions for hypertension treatment, with the aim of providing new perspectives and approaches for future research and treatment of hypertension.

Purpose: This study aimed to examine the impact of CA on DN and elucidate its underlying molecular mechanisms of inflammation.

Methods: We fed C57BL/6 mice injected with streptozotocin to induce diabetes. In addition, we stimulated NRK-52E cells with 20 mmol/L d-glucose to mimic the diabetic condition.

Results: Our findings demonstrated that CA effectively reduced blood glucose levels, and improved DN in mice models. Additionally, CA reduced kidney injury and inflammation in both mice models and in vitro models. CA decreased high glucose-induced ferroptosis of NRK-52E cells by inducing GSH/GPX4 axis. Conversely, the ferroptosis activator or the PI3K inhibitor reversed positive effects of CA on DN in both mice and in vitro models. CA suppressed PAQR3 expression in DN models to promote PI3K/AKT activity. The PAQR3 activator reduced the positive effects of CA on DN in vitro models. Moreover, CA directly targeted the PAQR3 protein to enhance the ubiquitination of the PAQR3 protein.

Conclusion: Overall, our study has uncovered that CA promotes the ubiquitination of PAQR3, leading to the attenuation of ferroptosis in DN. This effect is achieved through the activation of the PI3K/AKT signaling pathways by disrupting the interaction between PAQR3 and the P110α pathway. These findings highlight the potential of CA as a viable therapeutic option for the prevention of DN and other forms of diabetes.

Objective: This study aims to explore the current cognitive status and identify risk factors associated with cognitive function in Tibetan hypertensive patients living at various altitudes.

Methods: The Simple Mental Status Scale (MMSE) was used to evaluate the cognitive function of 611 Tibetan hypertensive patients at various altitudes in Gannan Tibetan Autonomous Prefecture. Afterward, we conducted an analysis to identify the factors influencing their cognitive function.

Results: The study found that the prevalence of cognitive dysfunction was 22.3%, with a higher incidence at high altitude (group D 29.0%) compared to low altitude (group A 16.0%). The study conducted a binary logistic regression analysis to identify the risk factors for cognitive dysfunction. The analysis revealed that altitude, age, body mass index, marital status, education, income level, and blood pressure control level were all significant risk factors. After controlling for age, body mass index, marital status, educational level, income level, and blood pressure control level, the risk of developing cognitive dysfunction was 2.773 times higher (p < .05) for individuals in group C at high altitude and 2.381 times higher (p < .05) for individuals in group D at high altitude compared to those in group A at low altitude.

Conclusions: Altitude plays a role in the development of cognitive dysfunction in hypertensive patients. Tibetan hypertensive patients living at high altitudes may be at a higher risk of cognitive dysfunction compared to those living at lower altitudes. Therefore, interventions should be targeted to prevent or mitigate potential cognitive impairment.

To investigate the research levels, hotspots, and development trends regarding microRNAs in hypertension, this study conducted a visual analysis of studies on miRNA in hypertension based on the Web of Science core collection database using CiteSpace and VOSviewer analysis software along with literature from 2005-2023 as information data. Using citation frequency, centrality, and starting year as metrics, this study analyzed the research objects. It revealed the main research bodies and hotspots and evaluated the sources of literature and the distribution of knowledge from journals and authors. Finally, the potential research directions for miRNAs in hypertension are discussed. The results showed that the research field is in a period of vigorous development, and scholars worldwide have shown strong interest in this research field. A comprehensive summary and analysis of the current research status and application trends will prove beneficial for the advancement of this field.

Purpose: Hyperuricemia (HUA) is an important factor leading to chronic kidney disease (CKD). The kidney tubular inflammatory response is activated in HUA. This study aimed to investigate whether lactate dehydrogenase A (LDHA) is involved in mediating uric acid-induced kidney tubular inflammatory response.

Methods: In vivo, an HUA mouse model was established by continuous intraperitoneal injection of potassium oxonate (PO) for one week. A total of 18 C57BL/6J male adult mice were divided into three groups: control group, HUA group, and HUA+oxamate group, with six mice in each group. Oxamate was intraperitoneally injected into the mice one hour after PO injection. In vitro, an HUA model was simulated by stimulating HK-2 cells with uric acid. Oxamate and tempol inhibited LDHA and reactive oxygen species (ROS) in HK-2 cells.

Results: In HUA mice, blood uric acid levels were significantly elevated. LDHA in kidney tubular cells was significantly increased in both in vivo and in vitro HUA models, accompanied by an increase in kidney tubular inflammation and ROS. Mechanistically, LDHA mediates uric acid-induced inflammation to kidney tubular cells through the ROS/NLRP3 pathway. Pharmacologic inhibition of LDHA or ROS in kidney tubular cells can significantly ameliorate inflammation response caused by uric acid.

Conclusions: LDHA in kidney tubular cells significantly was increased in HUA models. LDHA mediates kidney inflammation response induced by uric acid through the ROS/NLRP3 pathway. This study may provide a new intervention target for preventing kidney tubular inflammation caused by uric acid.

Purpose: Hypertensive disorder complicating pregnancy (HDCP) is a serious clinical disorder syndrome during pregnancy. This study aims at finding novel targets for HDCP therapy.

Methods: HDCP-related mRNAs were firstly screened out and subjected to gene enrichment analysis. We chose protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) as the research object. Thirty-nine HDCP patients at 32 to 40 weeks of gestation were selected as the HDCP group, and 39 normal controls who received cesarean section delivery at 37-42 weeks of pregnancy were enrolled in this study. Chorionic villi samples were collected within 30 min of delivery. The apoptosis of isolated placental trophoblasts was monitored to investigate the regulatory role of PRKAA2.

Results: PRKAA2 expression was further proven to be enhanced in the placental tissues of HDCP patients compared with that of normal puerpera. Subsequently, the results of flow cytometry analysis and western blot indicated that PRKAA2 overexpression accelerated primary placental cell apoptosis, while its knockdown attenuated cell apoptosis. Mechanistically, we determined that the level of PRKAA2 succinylation was elevated in the placental tissue of HDCP patients. Through in vitro succinylation assay and mutagenesis, we confirmed that sirtuin 5 (SIRT5) interacts with PRKAA2 at K69 and K260 to induce PRKAA2 desuccinylation. SIRT5 regulated primary HDCP cell apoptosis through PRKAA2. Finally, the animal study revealed that PRKAA2 elevates the systolic blood pressure of HDCP rat model.

Conclusion: Our findings indicated that SIRT5-mediated PRKAA2 succinylation modulates placental cell apoptosis in HDCP, suggesting that PRKAA2 is a potential therapeutic target for HDCP treatment.

Objectives: Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl^-1/mIU∙l^-1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD).

Methods: Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995-1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl^-1/mIU∙l^-1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening.

Results: In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19-1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41-3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62-1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension.

Conclusions: The CVD risk-based optimal ARR cutoff is 1.0 ng·dl^-1/mIU∙l^-1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk.

Clinical trial registration: ClinicalTrials.gov (NCT03224312).

Background: Fibroblast growth factor 21 (FGF21) has a protective effect against cardiovascular disease. However, the role of FGF21 in hypertension remains elusive.

Methods: Ten-week-old male C57BL/6 mice were randomly divided into normal-salt (NS) group, NS+FGF21 group, deoxycorticosterone acetate-salt (DOCA) group and DOCA+FGF21 group. The mice in NS group underwent uninephrectomy without receiving DOCA and 1% NaCl and the mice in DOCA group were subjected to uninephrectomy and DOCA-salt (DOCA and 1% NaCl) treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF) or FGF21 (1 mg/kg) into the bilateral paraventricular nucleus (PVN) of mice.

Results: Here, we showed that FGF21 treatment lowered DOCA salt-induced inflammation and oxidative stress in the PVN, which reduced sympathetic nerve activity and hypertension. Mechanistically, FGF21 treatment decreased the expression of HNF4α and inhibited the binding activity of HNF4α to the promoter region of ACE2 in the PVN of DOCA salt-treated mice, which further up-regulated ACE2/Ang (1-7) signals in the PVN. In addition, ACE2 deficiency abolished the protective effect of FGF21 in DOCA salt-treated mice, suggesting that FGF21-mediated antihypertensive effect was dependent on ACE2.

Conclusions: The results demonstrate that FGF21 protects against salt-sensitive hypertension via regulating HNF4α/ACE2/Ang (1-7) axis in the PVN of DOCA salt-treated mice via multi-organ crosstalk between liver, brain and blood vessels.