Clinical and Experimental Hypertension最新文献

Objective: To introduce bilateral hypertensive retinopathy (HR) (grade 4) complicated with macular edema (ME) patients with binocular intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) treatment.

Methods: Three cases of hypertensive retinopathy were observed. The fundus examination was consistent with HR (grade 4). The patients received anti-VEGF intraocular injection.

Results: The patient's ME and optic nerve edema were significantly reduced, visual acuity was significantly improved, and a case of secondary choroidal neovascularization (CNV) in the fundus of HR (grade 4) was also noted.

Conclusions: The use of intravitreal anti-VEGF agents in stage IV hypertensive retinopathy appears satisfactory but not perfect. In severe cases with vitreous hemorrhage, early injection avoids vitrectomy.

Regular exercise training can significantly improve the gut environment and influence the metabolic activity of the gut microbiota. These changes promote the production of beneficial metabolites, which may modulate blood pressure regulation through multiple mechanisms. The beneficial microbial species including Faecalibacterium prausnitzii, Bifidobacterium spp., Lactobacillus spp., Roseburia spp.,and Bacteroides spp. These beneficial microbes produce various metabolites during metabolism, including short-chain fatty acids, vitamins, lactic acid, bileacids, and gamma-aminobutyric acid. These metabolites are not only essential for maintaining gut health but also positively influence hypertension by modulating the nervous system, immune system, and improving metabolic function. This review aims to elucidate the complex interactions among exercise training, gut microbiota, and hypertension.

Background: Circulating microRNA-210-3p (miR-210-3p) is a hypoxia-related regulator implicated in placental maladaptation. Its longitudinal behavior across hypertensive disorders of pregnancy (HDP), and whether low-dose aspirin modifies its trajectory, remain insufficiently understood.

Methods: This prospective case-control study was conducted between October 2021 and November 2024. Circulating miR-210-3p was measured in the first trimester and at delivery. Aspirin use followed routine clinical practice for preeclampsia prevention. Longitudinal trajectories were examined using generalized estimating equations (GEE) as the primary analytic approach and linear mixed effects models (LMM) as a secondary method.

Results: Ninety-four women were enrolled, including 73 controls, 11 with gestational hypertension, and 10 with preeclampsia. miR-210-3p increased significantly from the first trimester to delivery in gestational hypertension (p = 0.003) and preeclampsia (p = 0.006), with no significant change in controls. In the first trimester, gestational hypertension exceeded controls (p = 0.006), and preeclampsia exceeded both groups (both p < 0.001). At delivery, gestational hypertension and preeclampsia remained higher than controls (both p < 0.001), and preeclampsia exceeded gestational hypertension (p = 0.036). GEE demonstrated a significantly slower rise in miR-210-3p among aspirin users with gestational hypertension (p = 0.042), and this association strengthened in sensitivity analysis (p = 0.001). LMM showed a similar, non-significant trend.

Conclusion: miR-210-3p exhibited disorder-specific longitudinal patterns across HDP. Aspirin-associated changes were observed in gestational hypertension but not in preeclampsia, suggesting differences in molecular expression trajectories between the two conditions over the course of gestation, while the underlying biological mechanisms remain to be clarified.

Background: Malignant hypertension (mHTN) is a severe hypertensive emergency, often associated with renal deterioration. Kidney length may be of useful to identify patients with renal dysfunction. Whether kidney length in mHTN patients is associated with renal prognosis is unclear.

Methods: The study enrolled 280 mHTN patients with renal thrombotic microangiopathy (TMA) who underwent renal biopsy between 2008 and 2023. Linear regression was used to explore patient characteristics of kidney length. The association between kidney length and ≥15% increase in estimated glomerular filtration rate (eGFR), and end-stage renal disease (ESRD) was analyzed using Cox regression and logistic regression, respectively. Kidney length was analyzed in tertiles, using the first tertile as reference.

Results: Patients with larger kidney length had higher levels of body mass index (BMI) and eGFR, but lower levels of urea nitrogen, serum creatinine, uric acid, global sclerosis ratio, and tubular atrophy/interstitial fibrosis ratio. Kidney length was strongly positively correlated with BMI, and negatively related to tubular atrophy/interstitial fibrosis ratio. During the follow-up, 72 patients experienced a ≥15% increase in eGFR and 172 patients progressed to ESRD. Patients in the third tertile of kidney length had a better renal recovery outcome of ≥15% increase in eGFR and lower odds of ESRD.

Conclusions: In mHTN patients with renal TMA, large kidney length is associated with better renal function improvement of ≥15% increase in eGFR, and lower risk of ESRD. In clinical practice, the measurement of kidney length may serve as a non-invasive indicator to assess renal prognosis and inform timely treatment interventions in mHTN patients.

Heart failure (HF) is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. Globally, the morbidity and mortality of HF are still on the rise, especially in elderly individuals, and the low 5-year survival rate of HF is a major social and health management problem. The pathogenesis of heart failure involves genetic factors and persistent cardiac inflammation. Genetic factors typically increase a patient's susceptibility to specific diseases. Notably, persistent cardiac inflammation is also a significant contributor to heart failure. Whether it is spontaneous aseptic inflammation of the heart or inflammation caused by infection, both can lead to excessive activation of the immune system, thereby triggering adverse cardiac remodeling. This review focuses on describing the inflammatory/immune activation mechanisms involved in heart failure and explores targeted drugs for inflammatory/immune activation. Additionally, we focused on the NLRP3 inflammasome (a cellular signaling protein complex), whose excessive activation produces large number of inflammatory factors, including IL-1β and IL-18, ultimately leading to persistent inflammation and excessive immune activation in the myocardium, which in turn triggers myocardial cell death and adverse remodeling. We have revealed the pathogenic role of NLRP3 in heart failure, providing a theoretical basis for further research into heart failure.

The unregulated use of highly purified arachidonic acid (AA) supplements among Chinese fitness enthusiasts raises concerns about cardiovascular safety. To evaluate these risks, we integrated population-based, genetic, and experimental evidence. Cross-sectional analysis of NHANES data demonstrated a higher risk of hypertension in individuals within the highest AA intake quartile (OR = 1.262, 95% CI: 1.109-1.438, P < 0.001). Two-sample Mendelian randomization confirmed causal effects of AA metabolites, including thromboxane (OR = 1.006, P < 0.001), eicosanoid C20H28O4 (OR = 1.305, P = 0.009), and 20-HETE-related C20H32O3 (OR = 1.290, P = 0.043). Single-cell transcriptomic profiling revealed increased renal expression of CYP4A11 in hypertensive patients, supporting a mechanistic link between AA metabolism and blood pressure regulation. In vivo, Wistar-Kyoto and spontaneously hypertensive rats fed a high-dose AA diet for six weeks exhibited significant elevations in systolic, diastolic, and mean arterial pressure, accompanied by increased renal vascular resistance. Mechanistic analyses showed that AA upregulated CYP4A1 expression and enhanced 20-HETE production without altering thromboxane synthase activity. Histological assessments revealed glomerular edema, tubular injury, and marked cardiac and renal fibrosis in AA-treated animals. Together, these convergent findings indicate that chronic high-dose AA intake promotes hypertension and multiorgan fibrosis via CYP4A/20-HETE activation. These results highlight the translational importance of AA metabolism in cardiovascular disease and underscore the need for regulatory oversight of AA supplements and therapeutic targeting of this pathway.

Background: Renal denervation (RDN) has emerged as a potential therapeutic option for resistant hypertension (HT), which remains a major clinical challenge due to poor blood pressure (BP) control despite optimized pharmacotherapy. This study aimed to assess the safety and effectiveness of catheter-based RDN in resistant hypertension patients, based on our center's experience.

Methods: This retrospective, single-center study included 120 patients with resistant HT who were eligible for RDN and underwent the procedure using the Symplicity Spyral system between January 2023 and December 2024. Office systolic and diastolic BP were assessed at baseline and 6 months after RDN. The primary endpoint was the reduction in BP, while secondary endpoints included changes in the number of antihypertensive medications.

Results: At 6 months, office systolic BP decreased significantly from 156 ± 7.7 mmHg to 143 ± 3.7 mmHg, while diastolic BP declined from 93.5 ± 5.5 mmHg to 90 ± 3.9 mmHg (both p < 0.001). Median per-patient reductions were 13 mmHg systolic and 3.5 mmHg diastolic. The mean number of antihypertensive medications decreased from 4.88 ± 0.9 to 4.47 ± 1.1 (p < 0.001). Minor adverse events included acute kidney injury in two patients (1.7%) and femoral artery injury in one patient (0.8%).

Conclusion: Catheter-based RDN using the Symplicity Spyral system was safe and effective in reducing BP and medication burden in patients with resistant HT. These results support RDN as a potential therapeutic option in appropriately selected patients.

Objective: Perivascular adipose tissue (PVAT) is closely related to the pathogenesis of vascular remodeling in hypertension. The objective of this study was to explore the specific molecular mechanisms underlying the role of PVAT in the onset and progression of hypertensive vascular remodeling.

Methods: Thoracic aorta PVAT from male spontaneously hypertensive rats (SHRs) and male Wistar-Kyoto (WKY) rats was used for proteomic analysis, and the differential expression of the identified target proteins was verified by western blotting, immunohistochemistry and transmission electron microscopy (TEM). In vitro, FUN14 domain-containing 2 (FUNDC2) expression was knocked down in 3T3-L1 adipocytes to assess its effects on mitochondrial dynamics, ferroptosis, and adipokine secretion. Next, vascular smooth muscle cells (VSMCs) were cultured in the supernatant of the adipocytes to detect changes in their phenotypic switching and migration.

Results: The proteomic results revealed that the expression of the outer mitochondrial membrane protein FUNDC2 was significantly upregulated in the PVAT of SHRs. Additionally, the expression of key proteins that regulate mitochondrial dynamics and ferroptosis was altered significantly in the PVAT of SHRs compared with the PVAT of WKY rats. Upon FUNDC2 knockdown in 3T3-L1 adipocytes, proteins related to mitochondrial dynamics, ferroptosis, and adipokines reversed the changes in their expression. Moreover, in VSMCs cultured with the supernatant of FUNDC2-knockdown adipocytes, the VSMC phenotype and migration changed.

Conclusion: Our findings indicated that increased FUNDC2 expression might lead to PVAT dysfunction and abnormal adipokine secretion, potentially through its link to mitochondrial dynamics and ferroptosis in PVAT adipocytes, therefore leading to hypertensive vascular remodeling.

Background: Atherosclerosis (AS) is a complex cardiovascular disorder driven by endothelial cell dysfunction and immune microenvironment dysregulation. We identified novel endothelial-related diagnostic biomarkers through multi-omics integration and machine learning approaches.

Methods: Single‑cell atlas of AS was constructed from scRNA-seq data using the Seurat. Endothelial cell‑specific co‑expression modules and hub genes were identified via high-dimensional WGCNA (hdWGCNA), and key endothelial‑associated differentially expressed genes (DEGs) were obtained by integrating these modules with differential expression analysis. Diagnostic genes were screened using LASSO regression and SVM-RFE using glmnet and caret packages, respectively. Their correlations with immune cell infiltration were assessed by single-sample GSEA (ssGSEA) and the CIBERSORT algorithm. Finally, the binding capacity of the encoded proteins to potential therapeutic agents was evaluated through drug-target prediction using the Enrichr platform and the DSigDB database, followed by molecular docking simulations.

Results: A total of 66 endothelial cell-associated DEGs were identified, from which four core feature genes (ANXA2, DBN1, ZNF385D, and IL6ST) were screened using machine learning approaches. Immune infiltration analysis revealed a global increase in immune cell infiltration (e.g., activated B cells, T cells, and macrophages) in atherosclerotic lesions, with the four genes showing significant correlations with specific immune subsets, while single-cell data further confirmed T cells, macrophages, and B cells as the predominant cellular components in the plaque microenvironment. Molecular docking results demonstrated strong binding capabilities of ANXA2 with thalidomide and IL6ST with resveratrol, with binding energies of -6.7 kcal/mol and -7.4 kcal/mol, respectively.

Conclusion: Our findings provided new insights for the targeted AS therapy.

Objective: To evaluate the apolipoprotein B (ApoB) to apolipoprotein A-I (ApoA-I) ratio as a biomarker for coronary heart disease (CHD) and its clinical phenotypes, beyond traditional lipid parameters.

Methods: This single-center, case-control study analyzed 7,277 patients undergoing coronary angiography. Multivariable logistic regression assessed the independent association of the ApoB/ApoA-I ratio with CHD, acute myocardial infarction (AMI), multivessel disease (MVD), and percutaneous coronary intervention (PCI). Predictive performance was evaluated via ROC curve analysis, with prespecified subgroup analyses.

Results: The ApoB/ApoA-I ratio was the strongest independent lipid predictor of CHD (adjusted OR 4.49, 95% CI 1.98-10.19). It significantly predicted severe clinical phenotypes: AMI (OR 1.94, 95% CI 1.44-2.62), MVD (OR 1.67, 95% CI 1.24-2.26), and PCI requirement (OR 1.95, 95% CI 1.43-2.66). The ratio showed significant discriminatory power for all endpoints (AUCs 0.569-0.608). Subgroup analyses revealed markedly stronger associations in males, older adults (≥60 years), and hypertensive patients, but substantially attenuated predictive value in diabetic patients.

Conclusion: The ApoB/ApoA-I ratio is a superior biomarker for CHD risk stratification, particularly for identifying severe disease manifestations and guiding revascularization decisions in specific patient subgroups. Its integration into clinical practice could enable more precise cardiovascular risk management.