Vildagliptin improves high glucose-induced endothelial mitochondrial dysfunction via inhibiting mitochondrial fission.

The dipeptidyl peptidase 4 inhibitor vildagliptin (VLD), a widely used anti-diabetic drug, exerts favourable effects on vascular endothelium in diabetes. We determined for the first time the improving effects of VLD on mitochondrial dysfunction in diabetic mice and human umbilical vein endothelial cells (HUVECs) cultured under hyperglycaemic conditions, and further explored the mechanism behind the anti-diabetic activity. Mitochondrial ROS (mtROS) production was detected by fluorescent microscope and flow cytometry. Mitochondrial DNA damage and ATP synthesis were analysed by real time PCR and ATPlite assay, respectively. Mitochondrial network stained with MitoTracker Red to identify mitochondrial fragmentation was visualized under confocal microscopy. The expression levels of dynamin-related proteins (Drp1 and Fis1) were determined by immunoblotting. We found that VLD significantly reduced mtROS production and mitochondrial DNA damage, but enhanced ATP synthesis in endothelium under diabetic conditions. Moreover, VLD reduced the expression of Drp1 and Fis1, blocked Drp1 translocation into mitochondria, and blunted mitochondrial fragmentation induced by hyperglycaemia. As a result, mitochondrial dysfunction was alleviated and mitochondrial morphology was restored by VLD. Additionally, VLD promoted the phosphorylation of AMPK and its target acetyl-CoA carboxylase in the setting of high glucose, and AMPK activation led to a decreased expression and activation of Drp1. In conclusion, VLD improves endothelial mitochondrial dysfunction in diabetes, possibly through inhibiting Drp1-mediated mitochondrial fission in an AMPK-dependent manner.

Alpinetin enhances cholesterol efflux and inhibits lipid accumulation in oxidized low-density lipoprotein-loaded human macrophages.

Alpinetin is a natural flavonoid abundantly present in the ginger family. Here, we investigated the effect of alpinetin on cholesterol efflux and lipid accumulation in oxidized low-density lipoprotein (ox-LDL)-treated THP-1 macrophages and human peripheral blood monocyte-derived macrophages (HMDMs). After exposing THP-1 macrophages to alpinetin, cholesterol efflux was determined by liquid scintillator. The mRNA and protein levels of peroxisome proliferator-activated receptor gamma (PPAR-γ), liver X receptor alpha (LXR-α), ATP-binding cassette transporter A1 (ABCA1), and ABCG1 and scavenger receptor class B member 1 were determined by reverse-transcriptase PCR (RT-PCR) and Western blot analysis, respectively. Alpinetin promoted apolipoprotein A-I- and high-density-lipoprotein-mediated cholesterol efflux and elevated PPAR-γ and LXR-α mRNA and protein expression in a dose-dependent fashion in ox-LDL-treated THP-1 macrophages and HMDMs. Small interfering RNA-mediated silencing of PPAR-γ or LXR-α dose dependently reversed alpinetin-increased cholesterol efflux in THP-1 macrophages, indicating the involvement of PPAR-γ and LXR-α in alpinetin-promoted cholesterol efflux. Alpinetin inhibited ox-LDL-induced lipid accumulation and enhanced the expression of ABCA1 and ABCG1 mRNA and protein, which was reversed by specific knockdown of PPAR-γ or LXR-α. Taken together, our results reveal that alpinetin exhibits positive effects on cholesterol efflux and inhibits ox-LDL-induced lipid accumulation, which might be through PPAR-γ/LXR-α/ABCA1/ABCG1 pathway.

Cost-utility analysis of add-on dapagliflozin in heart failure with preserved or mildly reduced ejection fraction.

AIMS: The DELIVER study demonstrates a significant improvement in cardiovascular death or hospitalization for heart failure among heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF).Cost-utility of the adjunct use of dapagliflozin to standard therapy among patients with HFpEF or HFmrEF remains unclear. METHODS AND RESULTS: A five-state Markov mode was constructed to project health and clinical outcomes of the adjunct use of dapagliflozin to standard therapy among 65-year-old patients with HFpEF or HFmrEF. A cost-utility analysis was performed based on the DELIVER study and national statistical database. The cost and utility was inflated to 2022 by the usual discount rate of 5%. The primary outcomes were total cost and quality-adjusted life-years (QALYs) per patients as well as the incremental cost-effectiveness ratio. Sensitivity analyses were also applied. Over a 15 year lifetime horizon, the average cost per patient was $7245.77 and $5407.55 in the dapagliflozin group and the standard group, along with an incremental cost of $1838.22. The average QALYs per patient was 6.00 QALYs and 5.84 QALYs in the dapagliflozin group and the standard group, along with an incremental QALYs of 0.15 QALYs, resulting in the incremental cost-effectiveness ratio of $11 865.33/QALY, which was below the willingness-to-pay (WTP) of $12 652.5/QALY. The univariate sensitivity analysis indicated the cardiovascular death in both group was the most sensitive variable. Probability sensitivity analysis revealed that when the WTP thresholds were $12 652.5/QALY and $37 957.5/QALY, the probabilities of being cost-effective with dapagliflozin as an add-on were 54.6% and 71.6%, respectively. CONCLUSIONS: From a public healthcare system perspective, the adjunct use of dapagliflozin to standard therapy among patients with HFpEF or HFmrEF generated advantages in cost-effectiveness in China at a WTP of $12 652.5/QALY, which promoted the rational use of dapagliflozin for heart failure.

Acute myocardial infarction post-gastrointestinal bleeding: A clinical dilemma with poor prognosis.

Background: Gastrointestinal bleeding (GIB) complicating acute myocardial infarction (AMI) is a severe clinical condition with treatment contradiction and poor prognosis. This study aimed to evaluate the rate of in-hospital mortality in patients with GIB who subsequently suffered from AMI and to explore the potential risk factors for this condition. Methods: In this retrospective study, a total of 77 patients diagnosed with GIB, who subsequently suffered from AMI, were enrolled from January 2013 to March 2022. Demographic, laboratory, and clinical data were collected. The in-hospital mortality was the outcome of interest. Logistic regression analysis was used to investigate the potential risk factors of in-hospital mortality. Results: Among the 77 patients included in this study, 62 (80.52%) were males. The mean age of patients was 65.88 ± 12.15 years, and 48 patients (62.34%) were non-ST-segment elevation myocardial infarction (NSTEMI). There were 16 (20.78%) cases of in-hospital deaths. The subjects who died showed higher levels of white blood cell count (13.05 ± 5.76 vs. 9.31 ± 4.07 × 109/L, P = 0.003) and troponin I (TnI) (9.23 ± 9.17 vs. 4.12 ± 5.03 µg/L, P = 0.003). Besides, there were higher proportions of cardiogenic shock (81.25% vs. 26.23%, P < 0.001) and mechanical ventilator usage (75.0% vs. 11.48%, P < 0.001) among the patients who died. The multivariate logistic regression analysis showed that white blood cell count (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.02-1.39, P = 0.030), cardiogenic shock (OR 12.18, 95% CI 3.06-48.39, P = 0.017), and mechanical ventilator usage (OR 7.21, 95% CI 1.28-40.51, P = 0.025) were independently associated with in-hospital mortality. Conclusions: The in-hospital mortality of patients with GIB who subsequently develop AMI is high. White blood cell count, cardiogenic shock, and mechanical ventilator usage are independent predictors of in-hospital mortality.

Composite dietary antioxidant index was negatively associated with the prevalence of diabetes independent of cardiovascular diseases.

AIM: The association between composite dietary antioxidant index (CDAI) and diabetes remains unknown. Our study was to investigate the association of CDAI with diabetes. METHODS: A total of 11,956 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). The CDAI was calculated from the intake of six dietary antioxidants. Multivariable logistic regressions were performed to explore the associations between CDAI and the prevalence of diabetes and glycemic index. Non-linear associations were explored using restricted cubic splines. RESULTS: In the multivariate logistic regression model, the odds ratio (95% confidence interval) of CDAI associating with obesity was 0.98 (0.97-1.00; p = 0.033). Compared with the lowest quartile, the highest quartile was related to 0.84-fold risk of diabetes (0.71-0.99; p = 0.035). However, CDAI was not independently associated with fasting glucose and hemoglobin A1c. CONCLUSION: CDAI was negatively associated with diabetes and the relationship was independent of other traditional risk factors.

Mannose binding lectin-associated serine protease-1 is a novel contributor to myocardial ischemia/reperfusion injury.

BACKGROUND: The lectin pathway has been demonstrated to play a critical role in the pathological process of myocardial ischemia/reperfusion injury (IRI). Mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1), especially different from other components of the lectin pathway, mediates proinflammatory and procoagulant reactions independent of complement cascades. However, the role of MASP-1 in myocardial IRI remains unknown so far. METHODS: Myocardial IRI was established with 45 min ischemia and 24 h reperfusion in mice. C1 inhibitor, as the natural inhibitor of MASP-1, was administrated at 20 IU/Kg via tail vein 5 min before surgical operation. Cardiac function and myocardial infarct size were assessed. Myocardial histology and fibrosis were evaluated by H&E and Masson staining, respectively. Deposition of MASP-1, expression of PAR-1/4 and neutrophil extracellular traps (NET) were investigated on myocardium tissue by IHC staining. Cell apoptosis was detected by TUNEL assay. Levels of myocardial enzymes and proinflammatory cytokines were determined by ELISA. RESULTS: Inhibition of MASP-1 with C1 INH improved cardiac function and alleviated myocardium tissue injury (infarct size, enzymes, histology and fibrosis) after myocardial IRI. Deposition of MASP-1 and expression PAR-1, as well as NET formation in myocardial tissue were suppressed by MASP-1 inhibitor, while PAR-4 was elevated. Levels of apoptosis, HMGB-1 and IL-6 were lower after blocking MASP-1. Yet, IL-8 and TNF-α remained unchanged. CONCLUSIONS: MASP-1, as a new contributor, played a critical role in myocardial IRI. Inhibition of MASP-1 protected myocardial tissue from IRI probably via regulation of PARs/NET pathway. This may provide a novel target strategy against myocardial IRI.

Cost-utility analysis of empagliflozin in heart failure patients with reduced and preserved ejection fraction in China.

Objective: EMPEROR-Reduced and EMPEROR-Preserved studies showed the benefits of empagliflozin along with a reduction in cardiovascular death or hospitalisation for heart failure (HF). Our aim was to evaluate the economics and effectiveness of adding empagliflozin to the standard therapy for HF with reduced ejection fraction (HFrEF) and HF preserved ejection fraction (HFpEF) in China. Methods: A multistate Markov model was constructed to yield the clinical and economic outcomes of adding empagliflozin to the standard therapy for 65-year-old patients with HFrEF and HFpEF. A cost-utility analysis was conducted, mostly derived from the EMPEROR-Reduced study, EMPEROR-Preserved study, and national statistical database. All costs and outcomes were discounted at the rate of 5% per annum. The primary outcomes were total and incremental costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Sensitivity analyses were also performed. Results: In the HFrEF population, the 10-year incremental cost was $827.52 and the 10-year incremental QALY was 0.15 QALYs, resulting in an ICER of $5,612.06/QALY, which was below the WTP of $12,652.5/QALY. In the HFpEF population, compared with the control group, the incremental cost was $1,271.27, and the incremental QALY was 0.11 QALYs, yielding an ICER of 11,312.65 $/QALY, which was also below the WTP of $12,652.5/QALY. In the HFrEF and HFpEF populations, the results of a one-way sensitivity analysis showed that the risk of cardiovascular death in both groups was the most influential parameter. In the HFrEF population, a probability sensitivity analysis (PSA) revealed that when the WTP thresholds were $12,652.5/QALY and $37,957.5/QALY, the probabilities of being cost-effective with empagliflozin as an add-on were 59.4% and 72.6%, respectively. In the HFpEF population, the PSA results revealed that the probabilities of being cost-effective with empagliflozin as an add-on were 53.1% and 72.2%, respectively. Conclusion: Considering that the WTP threshold was $12,652.5/QALY, adding empagliflozin to standard therapy was proven to be a slightly more cost-effective option for the treatment of HFrEF and HFpEF from a Chinese healthcare system perspective, which promoted the rational use of empagliflozin for HF.

Research on the Damage of Adrenal Pheochromocytoma to Patients' Cardiovascular Vessels and Its Correlation with Hypertension.

Chromaffin cell-centered pheochromocytoma (Pheo) is a rare tumour. Pheochromocytoma and how it affects the heart will be the topic of this article. Due to the comparable symptoms and indications of the sympathetic nervous system, a pheochromocytoma might be difficult to detect early. There are also other frequent differential diagnoses that might delay the detection of a pheochromocytoma. One of the most common side effects of pheochromocytoma is unmanageable hypertension. Hypertensive crisis (extreme increases in blood pressure) can develop, which is a life-threatening condition that leads to strokes or arrhythmia. Estimated to affect African Americans significantly, they frequently go undetected due to a lack of resources or accessibility of services. Because this tumour is difficult to identify and its symptoms often resemble those of other diseases, it is frequently overlooked. A pheochromocytoma's long-term consequences can include cardiac muscle deterioration, congestive heart failure (CHF), a higher diabetes risk and possibly death. Masked hypertension (MH) is more common in people with adrenal pheochromocytoma, which has been related to an increased risk of heart disease. With the use of ambulatory blood pressure monitoring, this research set out to find out how common mental health issues are among people with APs. There were 85 participants in all, 43 of whom had APs and 42 of whom had the same age, gender, BMI, smoking and diabetes as the AP patients. Measurements were made of the BP and AP in both the diseased and control groups. Retrospective data collection was used to gather biochemical, hormonal and radiological information on the patients. The Pearson-Boltzmann CNN method was then used to assess risk based on the diagnosis results. Furthermore, depending on the risk score, more nonselective blockers (e.g., prazosin, doxazosin, terazosin, and metyrosine) have been used to lower perioperative catecholamine levels, hence reducing illness risk. After a successful surgical excision of the tumour, the recommended therapy can usually be stopped quickly.

Cost-effectiveness of empagliflozin for the treatment of heart failure with reduced ejection fraction in China.

Aim: To determine the pharmacoeconomics of empagliflozin for the treatment of heart failure (HF) with reduced ejection fraction in China and to provide evidence-based reference for clinical rational drug selection and medical decision-making. Research design and methods: We used the Markov model to evaluate the cost-effectiveness of empagliflozin for the treatment of HF with reduced ejection fraction (HFrEF). We evaluated the cost-effectiveness of the standard treatment in addition to empagliflozin (empagliflozin group) vs. the cost-effectiveness of the standard treatment alone (standard treatment group). Results: We found that each additional quality-adjusted life year (QALY) in the empagliflozin group costed $3,842.20 more, which was less than China's gross domestic product (GDP) per capita in 2021 ($11,981). The steady-state mortality in the two groups was the key factor affecting the incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analysis revealed that when the willingness-to-pay (WTP) threshold was one time the GDP per capita in 2021 ($11,981) and three times the GDP per capita in 2021 ($35,943), the probability of the empagliflozin group being cost-effective was 85.8 and 91.6%, respectively. Conclusion: Compared with the standard treatment alone, the addition of empagliflozin to the standard treatment was more cost-effective for the treatment of HFrEF in China.

An integration-free iPSC line ZZUNEUi028-A derived from a patient with hypertrophic cardiomyopathy carrying a heterozygous mutation (c. 1504 C > T) in MYBPC3 gene.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease often caused by sarcomeric gene mutations. MYBPC3 is one of the most common genes associated with HCM. In this study, we generated a human induced pluripotent stem cell line ZZUNEUi028-A from a 19-year-old male HCM patient with c. 1504C â†’ T in MYBPC3 gene using non-integrative Sendai viral reprogramming technology. This cell line expresses pluripotency markers, exhibits a normal male karyotype (46, XY) and can differentiate into all three germ layers in vitro. ZZUNEUi028-A can serve as a cell disease model in the understanding of HCM pathogenesis.

Clinical Characteristics and Risk Factors of In-Hospital Mortality in Patients With Acute Myocardial Infarction With Subsequent Gastrointestinal Bleeding: A Single-Center Experience.

Objective: Gastrointestinal bleeding (GIB) post acute myocardial infarction (AMI) is a severe clinical condition with a poor prognosis. The purpose of the study was to evaluate the rate of in-hospital mortality in patients with GIB post-AMI and to identify the potential risk factors of this situation. Methods: In this single-center retrospective study, a total of 154 patients diagnosed with AMI who subsequently suffered GIB were enrolled from October 2013 to December 2021. Demographic, laboratory, and clinical data were collected. The in-hospital mortality was the outcome of interest. Logistic regression analysis was used to investigate the potential risk factors of in-hospital mortality. Results: Among the 154 subjects included in the final analysis, the mean age was 65.58 ± 11.20 years, and 104 (67.53%) were males. GIB occurred in 11 patients after thrombolytic therapy, 50 patients after percutaneous coronary intervention (PCI), and 93 patients during drug conservative treatment. A total of 41 patients died in the hospital. The in-hospital mortality rate of the thrombolysis group, PCI group, and drug conservative treatment group was 27.27% (3/11), 28.00% (14/50), and 25.81% (24/93), respectively. There was no difference in the in-hospital mortality among the three groups. The multivariate logistic regression analysis showed that the peak levels of TnI (OR 1.07, 95% CI 1.02-1.12, P = 0.011), condition of cardiogenic shock after admission (OR 14.52, 95% CI 3.36-62.62, P < 0.001), and the use of the mechanical ventilator (OR 8.14, 95% CI 2.03-32.59, P = 0.003) were significantly associated with in-hospital mortality. Conclusion: Regardless of the treatment strategy for AMI, once GIB occurred, the prognosis was poor. High in-hospital mortality in patients with GIB post-AMI was independently associated with the peak levels of TnI, condition of cardiogenic shock, and the use of a mechanical ventilator.

Cost-Effectiveness of Adding SGLT2 Inhibitors to Standard Treatment for Heart Failure With Reduced Ejection Fraction Patients in China.

Objective: To evaluate the economics and effectiveness of adding dapagliflozin or empagliflozin to the standard treatment for heart failure (HF) for patients with reduced ejection fraction (HFrEF) in China. Methods: A Markov model was developed to project the clinical and economic outcomes of adding dapagliflozin or empagliflozin to the standard treatment for 66-year-old patients with HFrEF. A cost-utility analysis was performed based mostly on data from the empagliflozin outcome trial in patients with chronic heart failure and a reduced ejection fraction (EMPEROR-Reduced) study and the dapagliflozin and prevention of adverse outcomes in heart failure (DAPA-HF) trial. The primary outcomes were measured via total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Results: In China, compared to the standard treatment, although adding dapagliflozin to the standard treatment in the treatment of HFrEF was more expensive ($4,870.68 vs. $3,596.25), it was more cost-effective (3.87 QALYs vs. 3.64 QALYs), resulting in an ICER of $5,541.00 per QALY. Similarly, adding empagliflozin was more expensive ($5,021.93 vs. $4,118.86) but more cost-effective (3.66 QALYs vs. 3.53 QALYs), resulting in an ICER of $6,946.69 per QALY. A sensitivity analysis demonstrated the robustness of the model in identifying cardiovascular death as a significant driver of cost-effectiveness. A probabilistic sensitivity analysis indicated that when the willingness-to-pay was $11,008.07 per QALY, the probability of the addition of dapagliflozin or empagliflozin being cost-effective was 70.5 and 55.2%, respectively. A scenario analysis showed that the cost of hospitalization, diabetes status, and time horizon had a greater impact on ICER. Conclusion: Compared with standard treatments with or without empagliflozin, adding dapagliflozin to the standard treatment in the treatment of HFrEF in China was extremely cost-effective.

Serum extracellular vesicles containing MIAT induces atrial fibrosis, inflammation and oxidative stress to promote atrial remodeling and atrial fibrillation via blockade of miR-485-5p-mediated CXCL10 inhibition.

BACKGROUND: Atrial fibrillation (AF), a supraventricular arrhythmia that impairs cardiac function, is a main source of morbidity and mortality. Serum-derived extracellular vesicles (EVs) have been identified to carry potential biomarker or target for the diagnosis and treatment of AF. We intended to dissect out the role of lncRNA MIAT enriched in serum-derived EVs in AF. METHODS: MIAT expression was quantified in EVs isolated from serum samples of AF patients. Mouse and cell models of AF were developed after angiotensin II (Ang II) induction. Relationship between MIAT, miR-485-5p, and CXCL10 was identified. Ectopic expression and depletion assays were implemented in Ang II-treated mice or HL-1 cells, or those co-cultured with serum-derived EVs to explore the roles of EV-carried MIAT. RESULTS: MIAT was upregulated in EVs from serum samples of AF patients. Further analysis indicated that MIAT enriched in serum-derived EVs promoted atrial fibrosis, inflammation and oxidative stress, and aggravated the atrial remodeling and resultant AF. Mechanistically, MIAT bound to miR-485-5p and weakened its inhibitory role on the target CXCL10, which was responsible for the role of serum-derived EV containing MIAT in cellular fibrosis, oxidative stress and inflammation, and atrial remodeling in vivo. CONCLUSIONS: In conclusion, serum-derived EV containing MIAT facilitates atrial remodeling and exacerbates the AF by abolishing the miR-485-5p-mediated CXCL10 inhibition. This finding aids in the deeper understanding about the pathophysiology of AF.

The protective role of DPP4 inhibitors in atherosclerosis.

Diabetes is a chronic non-communicable disease whose incidence continues to grow rapidly, and it is one of the most serious and critical public health problems. Diabetes complications, especially atherosclerosis-related chronic vascular complications, are a serious threat to human life and health. Growing evidence suggests that dipeptidyl peptidase 4 (DPP4) inhibitors, beyond their role in improving glycemic control, are helpful in ameliorating endothelial dysfunction in humans and animal models of T2DM. In fact, DPP4 inhibitors have been shown by successive studies to play a protective effect against vascular complications. On one hand, in addition to their hypoglycemic effects, DPP4 inhibitors participate in the control of atherosclerotic risk factors by regulating blood lipids and lowering blood pressure. On the other hand, DPP4 inhibitors exert anti-atherosclerotic effects directly through multiple mechanisms, including improving endothelial cell dysfunction, increasing circulating endothelial progenitor cell (EPCs) levels, regulating mononuclear macrophages and smooth muscle cells, inhibiting inflammation and oxidative stress and improving plaque instability. Herein, we review the beneficial roles of DPP4 inhibitors in atherosclerosis as detailed.

IL-6-miR-210 Suppresses Regulatory T Cell Function and Promotes Atrial Fibrosis by Targeting Foxp3.

The aim of this study was to explore the role of IL-6-miR-210 in the regulation of Tregs function and atrial fibrosis in atrial fibrillation (AF). The levels of interleukin (IL)-6 and IL-10 in AF patients were detected by using ELISA. Proportions of Treg cells were detected by fluorescence activated cell sorting analysis in AF patients. The expression of Foxp3, α-SMA, collagen I and collagen III were determined by western blot. The atrial mechanocytes were authenticated by vimentin immunostaining. The expression of miR-210 was performed by quantitative real-time polymerase chain reaction (qRT-PCR). TargetScan was used to predict potential targets of miR-210. The cardiomyocyte transverse sections in AF model group were observed by H&E staining. The myocardial filaments were observed by masson staining. The level of IL-6 was highly increased while the level of IL-10 (Tregs) was significantly decreased in AF patients as compared to normal control subjects, and IL-6 suppressed Tregs function and promoted the expression of α-SMA, collagen I and collagen III. Furthermore, miR-210 regulated Tregs function by targeting Foxp3, and IL-6 promoted expression of miR-210 via regulating hypoxia inducible factor-1α (HIF-1α). IL-6-miR-210 suppresses regulatory T cell function and promotes atrial fibrosis by targeting Foxp3.

Nighttime blood pressure decline as a predictor of renal injury in patients with hypertension: a population-based cohort study.

We explored whether the nighttime blood pressure (BP) decline predicts renal function decline in a population-based cohort with primary hypertension. We measured the baseline ambulatory BP and glomerular filtration rate (GFR) in a cohort of 1,042 primary hypertensive patients. We repeated the GFR measurements and calculated the rate of GFR decline after a median follow-up of 5.8 years. The estimated GFR (eGFR) declined by -0.23 to -0.20 mL/min per year as the nighttime systolic BP (SBP), diastolic BP (DBP), and mean BP decline rates increased by 1% (P < 0.001). In the fully adjusted model, the nighttime SBP, DBP, and mean BP were all related to a steeper rate of eGFR decline by -0.25 to -0.22 mL/min per 1% increase. The adjusted multivariable results indicated that the odds of an eGFR decline were reduced by 46% when the nighttime SBP decline rate increased by 1% (OR= 0.54, 95% CI: 0.46-0.62). The restricted cubic spline model indicated a non-linear dose-response relationship with the nighttime SBP, DBP, and mean BP. Nighttime BP may be an important biomarker of renal function injury in hypertensive patients.

MicroRNA-133a improves the cardiac function and fibrosis through inhibiting Akt in heart failure rats.

OBJECTIVE: MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, have been implicated in the development and progression of heart failure. METHODS: The present study was undertaken to determine the roles of miR-133a on the anatomical, hemodynamic and fibrosis of heart in the chronic heart failure rats, and the downstream signaling pathway. RESULTS: The expression of miR-133a in the heart of chronic heart failure from patients or rats was decreased. The miR-133a mimic and miR-133a overexpression caused a decrease in the heart weight/body weight (HW/BW) and LVEDP, and an increase in the LVSP and +LV dP/dt(max) in the chronic heart failure rats. However, the miR-133a inhibitor promoted the HW/BW and LVEDP, and caused a decrease in the LVSP and LV dP/dt(max) in the chronic heart failure rats. The miR-133a mimic and miR-133a overexpression significantly caused a decrease in the fibrosis of heart in chronic heart failure rats. The Akt inhibitor TCN abolished the effects of miR-133a on the HW/BW and LVEDP decrease, LVSP and LV dP/dt(max) increase in the chronic heart failure rats. The miR-133a increased the expression of phosphorylated Akt in the heart of chronic heart failure rats. CONCLUSION: These results demonstrated that miR-133a improves the cardiac function and fibrosis through inhibiting Akt in heart failure rats.

The relations of abnormal pulse pressure to the cardiovascular risk factors and the cardiac function in adults from Hebei, Zhejiang, and Guangxi province of China.

To explore the correlations of abnormal pulse pressure (PP) with the cardiovascular risk factors and cardiac functions by analyzing the distributions of abnormal PP in Han adults aged 18-74 years in Hebei, Zhejiang, and Guangxi province to provide evidence for health management. A cross-sectional study was carried out in three provinces of China. Multi-phase, stratified, unequal proportional and cluster sampling was adopted to investigate the data obtained from 12,795 Han adults aged 18-74 years. The prevalence of cases with abnormal PP in the three provinces was 6.7 %. Abnormal PP was significantly associated with a number of cardiovascular risk factors including location, age, gender, and education (P < 0.05). Results from multivariable logistic regression analysis showed that abnormal PP was positively associated with age and BMI. Compared with the normal subjects, there was a statistically significant difference in the mean of high-normal blood pressure, IFG divided by gender and LCW (P < 0.05). There was no significant difference in the mean of high-normal TC, TG, and LDL-C and low-normal HDL-C (P > 0.05). Age has also been found to be a statistically significant factor (P < 0.05). Abnormal PP was common in Chinese Han adults aged 18-74 years, which was independently associated with cardiovascular risk factors and cardiac functions. Health management for Han adults with abnormal PP was strongly suggested.

The protective effect of Smilax glabra extract on advanced glycation end products-induced endothelial dysfunction in HUVECs via RAGE-ERK1/2-NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra Roxb. (SGR) is a traditional Chinese herb that has been used in folk for the treatment of diabetic vascular complications. Advanced glycation end products (AGEs)-induced endothelial dysfunction has been thought to be a major cause of diabetic vascular complications. The present study was conducted to investigate the protective effect of SGR extract on AGEs-induced endothelial dysfunction and its underlying mechanisms. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to 200 µg/ml AGEs to induce endothelial dysfunction. Acridine orange/ethidium bromide (AO/EB) fluorescence assay and Annexin-V/PI double-staining were performed to determine endothelium apoptosis. Dihydroethidium (DHE) fluorescence probe, SOD and MDA kits were used to evaluate oxidative stress. The effect of SGR extract on AGEs-induced TGF-beta1 expression was determined by immunocytochemistry and western blotting. Attenuations of SGR extract on receptor for AGEs (RAGE) expression, extracellular regulated protein kinases (ERK1/2) activation and NF-κB phosphorylation were determined by immunofluorescence assay and western blotting. The blockade assays for RAGE and ERK1/2 were carried out using a specific RAGE-antibody (RAGE-Ab) or a selective ERK1/2 inhibitor PD98059 in immunofluorescence assay. RESULTS: The pretreatment of SGR extract (0.125, 0.25 and 0.5 mg crude drug/ml) significantly attenuated AGEs-induced endothelium apoptosis, and down-regulated TGF-beta1 protein expression in HUVECs. It was also well shown that SGR extract could down-regulate dose-dependently ROS over-generation, MDA content, TGF-beta1 expression, ERK1/2 and NF-κB activation whereas increase significantly SOD activity. Furthermore, the AGEs-induced ERK1/2 activation could be attenuated by the blockade of RAGE-Ab (5 µg/ml) while the NF-κB activation was ameliorated by ERK1/2 inhibitor PD98059 (10 µM). CONCLUSION: These results indicated that SGR extract could attenuate AGEs-induced endothelial dysfunction via RAGE-ERK1/2-NF-κB pathways. Our findings suggest that SGR extract may be beneficial for attenuating endothelial dysfunction in diabetic vascular complications.