Clinical and Experimental Hypertension最新文献

Background: Obesity, especially visceral obesity, plays an important role in the progression of cardiovascular disease (CVD). The body roundness index (BRI) is a new measure of obesity that is considered to reflect visceral obesity more comprehensively than other measures. This study aims to evaluate the relationship between BRI and CVD risk in hypertensive patients with obstructive sleep apnea (OSA) and explore its superiority in predicting CVD.

Methods: The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD. The area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to assess which measures of obesity had the best predictive value for CVD risk.

Results: During a median follow-up period of 6.8 years, 324 participants suffered a CVD event. After multivariable adjustment, compared with the reference group (the first tertile), the HRs (95% CI) of CVD were 1.25 (95% CI, 0.93-1.70) and 1.74 (95% CI, 1.30-2.33) for subjects in the tertile 2 and tertile 3 groups, respectively. Compared with other measurement indicators, BRI has the highest predictive value for CVD risk [AUC: 0.627, 95% CI: 0.593-0.661]. The addition of the BRI to the fully adjusted multivariate model improved the predictive power for CVD, which was validated in the continuous NRI and the IDI (all P < .05).

Conclusions: BRI was significantly associated with the risk of CVD in hypertensive patients with OSA. Furthermore, BRI may improve CVD risk prediction in hypertensive patients with OSA.

Background: The relationship of cumulative non high-density lipoprotein-cholesterol (Cum-non-HDL-C) concentration with the risk of cardiovascular disease (CVD) in individuals with hypertension remains unclear.

Methods: In total 27 234 participants for whom three consecutive total cholesterol and HDL-C concentrations were available, and who did not have CVD, comprising 13 617 with hypertension and 13 617 without from 2006 to 2010. Participants were placed into four groups according to Cum-non-HDL-C. Cox proportional hazards models were used to evaluate the relationship between Cum-non-HDL-C and the risk of CVD.

Results: Over a median 11 years, 1,298 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, compared with participants with hypertension and Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios and 95% confidence intervals of CVD associated with Cum-non-HDL-C values of 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.23 (1.01, 1.34), 1.27 (1.04, 1.56), and 1.51 (1.13, 2.01), respectively. Compared with participants without hypertension and a Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios (95% confidence intervals) for the participants with hypertension and Cum-non-HDL-Cs < 130 mg/dl, 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.84 (1.55, 2.18), 2.16 (1.81, 2.59), 2.17 (1.73, 2.70), and 2.45 (1.12, 3.29), respectively.

Conclusions: A consistently high non-HDL-C concentration increases the risk of CVD in individuals with hypertension, as does prolonged exposure to a high non-HDL-C concentration. Thus, the achievement of target blood pressure and non-HDL-C concentrations should help reduce the risk of CVD in individuals with hypertension.

Objective: Excessive proliferation and migration of pulmonary arterial smooth muscle cell (PASMC) is a core event of pulmonary hypertension (PH). Regulators of G protein signaling 10 (RGS10) can regulate cellular proliferation and cardiopulmonary diseases. We demonstrate whether RGS10 also serves as a regulator of PH.Methods: PASMC was challenged by hypoxia to induce proliferation and migration. Adenovirus carrying Rgs10 gene (Ad-Rgs10) was used for external expression of Rgs10. Hypoxia/SU5416 or MCT was used to induce PH. Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were used to validate the establishment of PH model.Results: RGS10 was downregulated in hypoxia-challenged PASMC. Ad-Rgs10 significantly suppressed proliferation and migration of PASMC after hypoxia stimulus, while silencing RGS10 showed contrary effect. Mechanistically, we observed that phosphorylation of S6 and 4E-Binding Protein 1 (4EBP1), the main downstream effectors of mammalian target of rapamycin complex 1 (mTORC1) as well as phosphorylation of AKT, the canonical upstream of mTORC1 in hypoxia-induced PASMC were negatively modulated by RGS10. Both recovering mTORC1 activity and restoring AKT activity abolished these effects of RGS10 on PASMC. More importantly, AKT activation also abolished the inhibitory role of RGS10 in mTORC1 activity in hypoxia-challenged PASMC. Finally, we also observed that overexpression of RGS10 in vivo ameliorated pulmonary vascular wall thickening and reducing RVSP and RVHI in mouse PH model.Conclusion: Our findings reveal the modulatory role of RGS10 in PASMC and PH via AKT/mTORC1 axis. Therefore, targeting RGS10 may serve as a novel potent method for the prevention against PH."

Background: The vitamin D level in the blood is associated with the incidence of hypertension. The present study investigated whether or not calcitriol, an active form of vitamin D, reverses age-related hypertension.

Methods: Young (3-month-old) and aged (12-month-old) C57BL/6 male mice were administered with or without calcitriol at 150 ng/kg per day by oral gavage for 8 weeks. Blood pressure was measured by tail-cuff plethysmography and telemetry, and superoxide production in renal tissue was assessed by fluorescence imaging, and the protein expression of AP1/AT₁R signaling pathway was examined by Western blot.

Results: We showed that 24-hour renal sodium excretion was impaired and blood pressure was increased in aged mice, which was related to the enhancement of renal AT₁R expression and function. In addition, the expression of transcription factor AP1 (a dimer of c-Fos and c-Jun) and the binding of AP1 to the AT₁R promoter region was significantly enhanced, accompanied by decreased nuclear translocation of Nrf2, abnormal mitochondrial function including decreased ATP production, NAD⁺/NADH ratio and mtDNA copy numbers, and increased reactive oxygen species. Calcitriol increased 24-hour urinary sodium excretion and reduced blood pressure in aged mice. Mechanically, calcitriol increased the nuclear translocation of Nrf2, improved mitochondrial function, reduced AP1 binding ability to AT₁R promoter, which reversed enhanced AT₁R expression and function, and lowered blood pressure in aged mice.

Conclusions: Our findings indicated that calcitriol reversed age-related hypertension via downregulating renal AP1/AT₁R pathway through regulating mitochondrial function. Thus, calcitriol may be a valuable therapeutic strategy for age-related hypertension.

Objective: Endothelial dysfunction is a critical initiating factor in the development of hypertension and related complications. Follistatin-like 1 (FSTL1) can promote endothelial cell function and stimulates revascularization in response to ischemic insult. However, it is unclear whether FSTL1 has an effect on ameliorating endothelial dysfunction in spontaneously hypertensive rats (SHRs).

Methods: Wistar Kyoto (WKY) and SHRs were treated with a tail vein injection of vehicle (1 mL/day) or recombinant FSTL1 (100 μg/kg body weight/day) for 4 weeks. Blood pressure was measured by tail-cuff plethysmograph, and vascular reactivity in mesenteric arteries was measured using wire myography.

Results: We found that treatment with FSTL1 reversed impaired endothelium-dependent relaxation (EDR) in mesenteric arteries and lowered blood pressure of SHRs. Decreased AMP-activated protein kinase (AMPK) phosphorylation, elevated endoplasmic reticulum (ER) stress markers, increased reactive oxygen species (ROS), and reduction of nitric oxide (NO) production in mesenteric arteries of SHRs were also reversed by FSTL1 treatment. Ex vivo treatment with FSTL1 improved the impaired EDR in mesenteric arteries from SHRs and reversed tunicamycin (ER stress inducer)-induced ER stress and the impairment of EDR in mesenteric arteries from WKY rats. The effects of FSTL1 were abolished by cotreatment of compound C (AMPK inhibitor).

Conclusions: These results suggest that FSTL1 prevents endothelial dysfunction in mesenteric arteries of SHRs through inhibiting ER stress and ROS and increasing NO production via activation of AMPK signaling.

Background: Atherosclerosis has been recognized as a chronic inflammation initiated by dysfunction of endothelial cell that contributes to the increased morbidity and mortality of severe cardiovascular events. The reported important role of microRNA-98 (miR-98) in regulation of endothelial cell behaviors prompt us to hypothesize that miR-98 could be involved in the process of atherosclerosis.

Methods and results: The current research showed the miR-98 expression was gradually down-regulated in atherosclerotic mouse arteries isolated from ApoE ablation mice subjected to high fat diet. Additionally, a dramatically reduced miR-98 expression in endothelial cells administrated to oxidized low-density lipoprotein (Ox-LDL) but a slight down-regulated level was found in macrophages. Functionally, attenuated miR-98 expression promoted secretion of chemokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs) induced by Ox-LDL, which subsequently increased infiltration and pro-inflammatory genes expression of macrophages, as well as the foam cell formation. Mechanistically, in vitro experiments indicated that the endothelial cell dysfunction regulated by miR-98 knockdown was partially contributed by upregulated expression of HMGB1. Furthermore, the animal experiment with ApoE^-/- mice administrated with miR-98 inhibitor demonstrated that miR-98 silencing enhanced the atherosclerotic lesions in aorta and aortic sinus that were accompanied with increased adhesion molecules, chemokines, and pro-inflammatory markers expression.

Conclusion: MicroRNA-98 knockdown promoted endothelial cell dysfunction to affect the inflammatory state of macrophage and the development of atherosclerosis, at least partially, through direct targeting HMGB1. Collected, these data suggested that miR-98 could be a novel drug target for atherogenesis management.

Background: Thrombospondins (TSPs) play important roles in several cardiovascular diseases. However, the association between circulating (plasma) thrombospondin 2 (TSP2) and essential hypertension remains unclear. The present study was aimed to investigate the association of circulating TSP2 with blood pressure and nocturnal urine Na⁺ excretion and evaluate the predictive value of circulating TSP2 in subjects with hypertension.

Methods and results: 603 newly diagnosed essential hypertensive subjects and 508 healthy subjects were preliminarily screened, 47 healthy subjects and 40 newly diagnosed essential hypertensive subjects without any chronic diseases were recruited. The results showed that the levels of circulating TSP2 were elevated in essential hypertensive subjects. The levels of TSP2 positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and other clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity, and serum triglycerides, but negatively associated with nocturnal urine Na⁺ concentration and excretion and high-density lipoprotein cholesterol. Results of multiple linear regressions showed that HOMA-IR and nocturnal Na⁺ excretion were independent factors related to circulating TSP2. Mantel-Haenszel chi-square test displayed linear relationships between TSP2 and SBP (χ² = 35.737) and DBP (χ² = 26.652). The area under receiver operating characteristic curve (AUROC) of hypertension prediction was 0.901.

Conclusion: Our study suggests for the first time that the circulating levels of TSP2 may be a novel potential biomarker for essential hypertension. The association between TSP2 and blood pressure may be, at least in part, related to the regulation of renal Na⁺ excretion, insulin resistance, and/or endothelial function.

Background: Microcirculatory endothelial dysfunction is a complex phenomenon that contributes to the development of cardiovascular disease. However, the relationship between microcirculatory endothelial dysfunction and macrovascular disease remains incompletely understood. Fluid overload is a risk factor for cardiovascular mortality in patients undergoing peritoneal dialysis. Therefore, we investigated the effects of chronic fluid overload on both the microcirculation and macrocirculation in these patients.

Methods: Thirty patients undergoing peritoneal dialysis were included in this cross-sectional study. We measured their central blood pressure and pulse wave velocity, assessed their microvascular endothelial function using drug-induced iontophoresis with laser Doppler flowmetry, and determined the amount of fluid overload using bioimpedance. We conducted a Spearman correlation analysis, univariate analysis, and stepwise multivariate regression models to determine the associations among the hemodynamic parameters.

Results: Acetylcholine-induced iontophoresis with laser Doppler flowmetry showed a correlation with both brachial and central pulse pressure (PP), but not with pulse wave velocity. Fluid overload was associated with both central and brachial PP and remained an independent predictor of central PP even after adjusting for multiple factors. However, fluid overload was not associated with microcirculatory endothelial function.

Conclusion: In peritoneal dialysis patients, we observed a significant association between central PP and microvascular endothelial function, indicating a connection between macrocirculation and microcirculation. However, conclusive evidence regarding fluid overload as a mediator between these circulatory systems is lacking. Further research is needed to investigate this relationship.

Objectives: Hypertension is a chronic disease with multiple causative factors that involve metabolic disturbances and can cause various complications. However, the metabolic characteristics of hypertension at different stages are still unclear. This study aimed to explore the metabolic changes induced by hypertension at different ages.

Methods: Spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were divided into four groups according to age: 5-week-old SHR (n = 6), 5-week-old WKY rats (n = 6), 32-week-old SHR (n = 6), and 32-week-old WKY rats (n = 6). Metabolites were analyzed in primary tissues (serum, heart, lung, kidney, brain, and brown adipose) using a non-targeted metabolomics approach.

Results: Thirty-five metabolites and nine related metabolic pathways were identified in 5-week-old SHR, mainly related to the metabolism of amino acids. Fifty-one metabolites and seven related metabolic pathways were identified in the 32-week-old SHR, involving glycolysis, lipid, and amino acid metabolisms.

Conclusion: This experiment elucidates the metabolic profile of SHR at different ages and provides a basis for predicting and diagnosing hypertension. It also provides a reference for the pathogenesis of hypertension.

Introduction: Preeclampsia (PE) is a serious pregnancy syndrome. Advanced maternal age (≥ 35 years old) is one of the major risk factors of PE and placental aging is considered to be related to this disease. However, the mechanisms underlying these phenomena remain obscured.

Methods: Gene expression profiles of PE and non-PE placental samples were curated from the GSE75010 dataset. A diagnostic model was constructed and immune characteristics of PE subtypes were estimated.

Results: A total of 58 aging-related genes, which may be associated with PE, were identified. Among them, LEP and FLT1 may be key aging-related genes. Based on 5 top genes (PIK3CB, FLT1, LEP, PIK3R1, CSNK1E), a diagnostic nomogram for PE was built (AUC = 0.872 in the GSE75010 dataset). Three molecular subtypes were clustered, which had different immune and angiogenesis characteristics.

Conclusion: The present study suggests the potential implications of aging-related genes in diagnosing PE. Diverse immune characteristics may be involved in the placental aging of PE.