Hypertension combined with atherosclerosis increases the risk of heart failure in patients with diabetes.

The increase in heart failure risk in the diabetic population when hypertension and atherosclerosis are both present is still inconclusive. The aim of this study was to explore the effects of hypertension combined with atherosclerosis in diabetic population on the risk of heart failure. We selected 10,711 patients with diabetes who participated in the Kailuan study and completed brachial-ankle pulse wave velocity (baPWV) testing for statistical analysis. The subjects were divided into the non-hypertensive non-atherosclerotic, hypertensive, atherosclerotic, and hypertensive atherosclerotic groups based on their history of hypertension and atherosclerosis. At a median follow-up of 4.15 years, 227 cases of heart failure occurred. Compared with the non-hypertensive non-atherosclerotic group, the multifactorial Cox proportional risk regression model showed that the hazard ratio (HR) for heart failure in the hypertensive atherosclerotic group was 3.08 (95% confidence interval [CI]: 1.32-7.16), whereas the HR decreased to 2.38 (95% CI: 1.01-5.63) after gradual correction of lipid-lowering, glucose-lowering, and antihypertensive drugs. The subgroup analysis and sensitivity analysis were consistent with that of total population. In conclusion, patients with diabetes exposed to both hypertension and atherosclerosis had an increased heart failure risk, which was attenuated by the use of lipid-lowering, glucose-lowering, and antihypertensive drugs.

Increased arterial stiffness elevates the risk of heart failure in diabetic patients.

BACKGROUND: Previous studies have shown that arterial stiffness (AS) was a risk factor for heart failure (HF) in nondiabetic patients. We aimed to analyze this impact in a community-based diabetic population. METHODS: Our study excluded those who had HF before brachial-ankle pulse wave velocity (baPWV) measurement and included 9041 participants finally. Subjects were divided into the normal (<14 m/s), intermediate (14-18 m/s), and elevated baPWV groups (>18 m/s) based on baPWV values. Multivariate Cox proportional hazard model was used to analyze the effect of AS on HF risk. RESULTS: During the median follow-up of 4.19 years, 213 patients had HF. The results of Cox model showed that HF risk in the elevated baPWV group was 2.25 times higher than that in the normal baPWV group (95% confidence interval [CI]: 1.24-4.11). HF risk increased by 18% (95% CI:1.03-1.35) for every 1 additional standard deviation(SD)of baPWV. Restricted cubic spline results showed statistically significant overall and non-linear associations between AS and HF risk (P < 0.05). The subgroup analysis and sensitivity analysis were consistent with that of total population. CONCLUSIONS: AS is an independent risk factor for developing HF in the diabetic population, and AS exhibits a dose-response relationship with HF risk.

Colchicine for prevention of post-operative atrial fibrillation: Meta-analysis of randomized controlled trials.

Objective: This study intended to assess the efficacy of colchicine for prevention of post-operative atrial fibrillation (AF). Background: Post-operative AF is a common complication of surgery operations. Inflammation plays a crucial role in the pathogenesis of post-operative AF. Colchicine, a potent anti-inflammatory drug, may have a role in mitigating the incidence of post-operative AF. Methods: We searched Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Database of Chinese sci-tech periodicals (COVIP), and Wanfang Database for randomized controlled trials (RCTs) comparing colchicine versus placebo, or usual care for prevention of post-operative AF. The main outcome was the occurrence of AF post operation, which includes cardiac surgery, lung surgery, or pulmonary vein isolation. The estimated risk ratio (RR) for the occurrence of post-operative AF was evaluated using a random-effects model. The safety end point was the development of any side effects. Results: A total of 12 RCTs with 2274 patients were eventually included in this meta-analysis, where 1141 patients received colchicine and 1133 patients received placebo or usual care. Perioperative colchicine treatment was related to a decreased incidence of post-operative AF (RR: 0.65; 95% confidence interval [CI]: 0.56 to 0.75, p<0.001). Although the incidence of gastrointestinal side effects was increased with colchicine therapy when compared to placebo (RR = 2.49, 95% CI 1.85 to 3.34, p < 0.001), the incidence of major adverse events was not increased (RR = 0.86, 95% CI 0.46 to 1.60, p = 0.64). Conclusion: In conclusion, the results of our meta-analysis suggest that colchicine treatment could lower the incidence of post-operative AF. Further studies are needed to determine the optimal colchicine treatment regime to minimize the incidence of adverse events.

RCAN1 deficiency aggravates sepsis-induced cardiac remodeling and dysfunction by accelerating mitochondrial pathological fission.

OBJECTIVE: Cardiac dysfunction and remodeling are serious complications of sepsis and are the main causes of death in sepsis. RCAN1 is a feedback regulator of cardiac hypertrophy. Here, we aim to investigate the role of RCAN1 in septic cardiomyopathy. METHODS: Mice were randomly divided into control-WT, control-RCAN1-/-, LPS-induced WT and LPS-induced RCAN1-/- groups, some with Midiv-1 or KN93 treatment. The protein levels of RCAN1, p-ERK1/2, NFAT3, Drp1, p-Drp1, p-CaMKII in mouse hearts or cultured cardiomyocytes were determined by Western blotting. Myocardial function was assessed by echocardiography. Cardiac hypertrophy and fibrosis were detected by H&E and Masson's trichrome staining. Mitochondrial morphology was examined by transmission electron microscope. Serum level of LDH was detected by ELISA. RESULTS: Our data show that RCAN1 was downregulated in septic mouse heart and LPS-induced cardiomyocytes. RCAN1-/- mice showed a severe impairment of cardiac function, and increased myocardial hypertrophy and fibrosis. The protein levels of NFAT3 and p-ERK1/2 were significantly increased in the heart tissues of RCAN1-/- mice. Further, RCAN1 deficiency aggravated sepsis-induced cardiac mitochondrial injury as indicated by increased ROS production, pathological fission and the loss of mitochondrial membrane potential. Inhibition of fission with Mdivi-1 reversed LPS-induced cardiac hypertrophy, fibrosis and dysfunction in RCAN1-/- mice. Moreover, RCAN1 depletion promoted mitochondrial translocation of CaMKII, which enhanced fission and septic hypertrophy, while inhibition of CaMKII with KN93 reduced excessive fission, improved LPS-mediated cardiac remodeling and dysfunction in RCAN1-/- mice. CONCLUSIONS: Our finding demonstrated that RCAN1 deficiency aggravated mitochondrial injury and septic cardiomyopathy through activating CaMKII. RCAN1 serves as a novel therapeutic target for treatment of sepsis-related cardiac remodeling and dysfunction.

Corrigendum: Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells.

[This corrects the article DOI: 10.3389/fphys.2019.00223.].

Corrigendum: Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells.

[This corrects the article DOI: 10.3389/fphys.2019.00223.].

Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells.

Ischemia/reperfusion (I/R) injury induces irreversible oxidative stress damage to the cardiac myocytes. Many studies have revealed that propofol alleviates the important organelle-mediated injury from oxidative stress in vitro. However, it remains unclear whether propofol prevents I/R-induced DNA damage in cardiomyocytes. In our study, we established an oxygen glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells and found that propofol decreased reactive oxygen species (ROS) levels and suppressed cell apoptosis induced by OGD/R in H9c2 cells. In addition, propofol significantly reduced the molecular marker of DNA damage and inhibited double-strand breaks of DNA damage induced by OGD/R in H9c2 cells in a dose-dependent manner. Furthermore, we investigated the molecular mechanisms and demonstrated that propofol inhibited forkhead box O 1 (FoxO1) phosphorylation and increased FoxO1 nuclear translocation through inhibition of protein kinase B (Akt) and adenosine 5'-monophosphate-activated protein kinase (AMPK) pathways. The protective effects of propofol against oxidative stress-induced DNA damage were reversed by silencing FoxO1. Taken together, our results suggest that oxidative stress aggravates DNA damage and apoptosis in H9C2 cells, which can be reversed by propofol via FoxO1 nuclear translocation.

Propofol Ameliorates H9c2 Cells Apoptosis Induced by Oxygen Glucose Deprivation and Reperfusion Injury via Inhibiting High Levels of Mitochondrial Fusion and Fission.

Background: The cardioprotective effect of propofol on ischemia-reperfusion injury (I/R injury) is partly due to suppressing apoptosis. Mitochondrial dynamics are also involved in apoptosis. Mitochondrial fusion and fission lead to mitochondrial morphological changes. However, whether suppressing apoptosis effect of propofol against ischemia-reperfusion injury in the heart is via regulating mitochondrial morphology remains unclear. Methods: H9c2 cells underwent oxygen glucose deprivation (OGD) followed by reperfusion to simulate cardiomyocytes ischemia/reperfusion injury. Cell viability, apoptosis ratio and intracellular reactive oxygen species (ROS) were assessed, respectively. Mitochondrial membrane dynamin family proteins, extracellular signal regulated kinase 1 and 2 (ERK1/2), phosphorylated extracellular signal regulated kinase 1 and 2 (p-ERK1/2) and proteins related to intrinsic apoptosis pathways were detected by western blotting. The mitochondrial morphology and the distribution of dynamin-related protein 1 (Drp1) were observed by using laser confocal microscopy. Results: Propofol enhanced the survival of H9c2 cells, decreased ROS levels and inhibited apoptosis during oxygen glucose deprivation/reperfusion (OGD/R) injury. Mitochondrial fission in H9c2 cells was inhibited by propofol during OGD injury. Propofol alleviated high levels of mitochondrial fusion and fission during OGD/R in H9c2 cells, by regulating mitochondrial membrane remodeling dynamin family proteins. Propofol inhibited Drp1 colocalization with mitochondria in H9c2 cells during OGD/R injury. Moreover, Drp1 phosphorylation was inhibited by propofol through decreasing ERK activation during OGD/R injury. We found that propofol ameliorated H9c2 cells apoptosis during OGD/R via inhibiting mitochondrial cytochrome c release and caspase-9, caspase-6, caspase-7 and caspase-3 activation. Conclusion: Propofol suppresses H9c2 cells apoptosis during OGD/R injury via inhibiting intrinsic apoptosis pathway, which may be partly due to reducing high levels of mitochondrial fusion and fission induced by OGD/R injury.

Stepwise extraction of valuable components from red mud based on reductive roasting with sodium salts.

The feasibility of an integrated technological route for comprehensive utilization of red mud was verified in this study. Valuable components in the mud, including Fe2O3, Al2O3 and SiO2 were stepwise extracted by magnetic separation and sulfuric acid leaching from reduced red mud, and meanwhile TiO2 was enriched in the leaching residue. Sodium salts were proved to be favorable for the magnetic separation of metallic iron and the subsequent acid leaching of Al and Si, through facilitating the reduction of iron oxides and the growth of metallic iron grains, together with enhancing the activation of Al and Si components during the roasting process. After reductive roasting in the presence of 6% Na2CO3 and 6% Na2SO4, a magnetic concentrate containing 90.2% iron with iron recovery of 95.0% was achieved from the red mud by magnetic separation. Subsequently, 94.7% Fe, 98.6% Al and 95.9% Si were extracted by dilute sulfuric acid leaching from the upper-stream non-magnetic material, yielding a TiO2-rich material with 37.8% TiO2. Furthermore, value-added products of silica gel and Al(OH)3 were prepared from the leachate by ripening and neutralizing.