Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway.

Long noncoding RNAs (lncRNAs) are known to participate in the pathological process of cardiac hypertrophy. This study aimed to investigate the function of the lncRNA, myosin heavy-chain associated RNA transcript (Mhrt), in cardiac hypertrophy and its possible mechanism of action. Adult mouse cardiomyocytes were treated with angiotensin II (Ang II) and transfected with Mhrt; cardiac hypertrophy was evaluated by estimating atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy-chain levels, and cell surface area by reverse transcription-quantitative polymerase chain reaction, western blotting, and immunofluorescence staining. The interaction between the Mhrt/Wnt family member 7B (WNT7B) and miR-765 was assessed using a luciferase reporter assay. Rescue experiments were performed by analyzing the role of the miR-765/WNT7B pathway underlying the function of Mhrt. The results indicated that Ang II induced hypertrophy of cardiomyocytes; however, overexpression of Mhrt alleviated the Ang II-induced cardiac hypertrophy. Mhrt acted as a sponge for miR-765 to regulate the expression of WNT7B. Rescue experiments revealed that the inhibitory effect of Mhrt on myocardial hypertrophy was abolished by miR-765. Additionally, the knockdown of WNT7B reversed the suppression of myocardial hypertrophy induced by downregulating miR-765. Taken together, Mhrt alleviated cardiac hypertrophy by targeting the miR-765/WNT7B axis.

Co-simulation of hypertensive left ventricle based on computational fluid dynamics and a closed-loop network model.

OBJECTIVE: Hypertension is one of the most common chronic and cardiovascular diseases, with the largest number of deaths. According to clinical experience, long-term hypertension will cause cardiac hypertrophy and other complications, and heart structure remodeling will significantly change the energy characteristics of the heart chambers, and impair heart function. Research shows that, early hypertension can be diagnosed by the blood flow and energy loss in the left ventricle. Therefore, it is important to choose an appropriate method to simulate and predict the flow domain of this ventricle. METHODS: This study took the left ventricular flow field of patients with hypertensive myocardial hypertrophy as the research object, used MATLAB-SIMULINK to establish a closed-loop network cardiovascular model, provided flow boundary conditions for the computational fluid dynamics (CFD) numerical simulation method, and, finally, completed a co-simulation. RESULTS: This article compared the degree of agreement between the energy loss in different phases of the heart cavity and clinical experimental data and summarized the characteristics of the flow field in patients with hypertensive myocardial hypertrophy. The analysis of three simulation groups (control group, non-left ventricular hypertrophy group, and left ventricular hypertrophy [LVH] group) showed that the vortices in the LVH group were irregular and not fully developed, accompanied by significant energy loss. CONCLUSION: The simulation method used in this study is basically consistent with the clinical data. Myocardial hypertrophy has a significant influence on the blood flow of the left ventricle. Changes in the blood flow make the left ventricular vortex distribution abnormal during the rapid systole and rapid ejection periods, leading to a series of dangerous factors, including increased energy loss and a low cardiac ejection fraction.

A systematic review for the efficacy of coenzyme Q10 in patients with chronic kidney disease.

BACKGROUND: The effects of coenzyme Q10 (CoQ10) supplementation in chronic kidney disease (CKD) patients remain controversial. OBJECTIVE: A systematic review of current evidence was performed to systematically and comprehensively summarize the effects of CoQ10 on cardiovascular outcomes, oxidative stress, inflammation, lipid profiles, and glucose metabolism. METHODS: MEDLINE, EMBASE, and the Cochrane Library database (Cochrane Central Register of Controlled Trials) were searched to identify eligible studies investigating the effects of CoQ10 supplementation on patients with CKD. RESULTS: Twelve independent studies (including seventeen publications) were included in this systematic review. For CKD patients, six studies reported variable cardiovascular outcomes, which yielded inconsistent results. Regarding oxidative stress and inflammation, pooled analysis showed that CoQ10 supplementation significantly reduced malonaldehyde (WMD: - 1.15 95% CI - 1.48 to - 0.81) and high-sensitivity C reactive protein levels (WMD: - 1.18 95% CI - 2.21 to - 0.15). Regarding glucose metabolism, we found that CoQ10 supplementation resulted in significant improvements in HbA1c (WMD: - 0.80; 95% CI: - 1.35 to - 0.24) and QUICKI (WMD: 0.02; 95% CI: 0.01 to 0.03). The pooled results indicated that CoQ10 supplementation had no effects on total cholesterol, or LDL-cholesterol, or on HDL-cholesterol, and triglycerides. CONCLUSIONS: Our systematic review demonstrated that CoQ10 supplementation might have promising effects on oxidative stress. This work provided some clues that CoQ10 supplementation might have the potential to improve inflammation levels, glucose metabolism, cardiac structure, and cardiac biomarkers. However, the effects of CoQ10 supplementation should be confirmed in larger high-quality studies.

Sinomenine ameliorates cardiac hypertrophy by activating Nrf2/ARE signaling pathway.

Cardiac hypertrophy (CH) is a result of the physiological adaptation of the heart to coronary heart disease, hypertension, and other cardiovascular diseases. Sinomenine is extracted from Caulis Sinomenii. This study aimed to explore the specific mechanism of the action of sinomenine in cardiac hypertrophy (CH) via Nrf2/ARE signaling pathway in vivo and in vitro. To establish a model of CH, H9C2 cells were treated with angiotensin II (Ang II) and intraperitoneally injected with isoproterenol. Then the cells were treated with 50 and 100 µM sinomenine. TUNEL, HE, rhodamine-labeled phalloidin, and immunohistochemical staining were performed. Flow cytometry was used to measure apoptosis rates. mRNA expression of ANP, BNP, and ß-MHC was determined by qRT-PCR. Furthermore, western blotting was performed to analyze protein expression. After sinomenine treatment, the surface area and apoptosis rates were decreased. Furthermore, the mRNA expression of ANP, BNP, and ß-MHC, levels of reactive oxygen species and malondialdehyde, and protein expression of Caspase3 and Bax were down-regulated, and the protein expression of Bcl-2 was upregulated. Sinomenine activates the Nrf2/ARE signaling pathway, and inhibition of this signaling pathway reversed the effects of sinomenine. In animal experiments, sinomenine decreased the heart weight and left ventricular weight indices, as well as the expression of ANP, BNP, and ß-MHC. Furthermore, sinomenine reduced the apoptosis rate and relieved CH-related oxidative stress by activating the Nrf2/ARE signaling pathway. Together, these findings reveal that sinomenine is a potential candidate drug for CH treatment and further research is required to generalize the result in human subjects.

Vector Flow Mapping Application in Local Cardiac Function in Hypertension Assessment.

OBJECTIVE: This study aims to investigate the clinical significance of vector flow mapping (VFM) by observing and quantifying energy loss (EL) during different phases and in different left ventricle (LV) segments. METHODS: 42 healthy physical examination subjects and 89 patients with hypertension (HTN) were enrolled in the present study. The patients with HTN were divided into two groups: the left ventricular hypertrophy group (LVH) (n = 51) and the non-left ventricular hypertrophy group (NLVH) (n = 38), while the healthy patients were control group. VFM analysis software DSA-RS1 was used to calculate EL during the rapid filling phase (P1), slow filling phase (P2), atrial contraction phase (P3), and rapid ejection phase (P4). The energy loss of basal segment (EL-B), middle segment (EL-M) and apical segment (EL-A) of left ventricle in different phases was calculated and compared among the three groups. RESULTS: In controls, segmental EL showed a gradual increase from the apex to the base during diastole; however, the regularity was not found in the HTN patients. During both P1 and P2 EL-B, EL-M and EL-A were significantly higher in the NLVH group and the LVH group compared with the control group (P < 0.05). EL in LVH group was the highest among the three groups (P < 0.05). During P3, EL-B, EL-M and EL-A were increased in the NLVH group and LVH group compared with the control group. However, EL-M and EL-A in LVH group were significantly lower than the NLVH group (P < 0.05). During P4, EL of all segments was significantly higher in the NLVH group and LVH group compared with the control group (P < 0.05). CONCLUSION: VFM can visually quantify hydrodynamic LV changes in healthy subjects. The EL levels in the different LV segments during different phases were significantly higher in the patients with HTN compared with the healthy subjects.

Associations of coenzyme Q10 with endothelial function in hemodialysis patients.

BACKGROUND: Endothelial dysfunction is common in patients undergoing hemodialysis (HD). However, little is known about the relationship between endothelial dysfunction and coenzyme Q10 (CoQ10) levels in HD patients. METHODS: Eligible HD patients were enrolled in this study according to prespecified inclusion and exclusion criteria. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Plasma CoQ10, serum malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. The potential confounders identified by univariate analyses (P < 0.15) were selected in a stepwise multiple regression model. RESULTS: In total, 111 HD patients were enrolled in this study. The mean CoQ10 level was 633.53 ± 168.66 ng/mL, and endothelial dysfunction was prevalent (91.0%) using a cut-off value of 10% FMD. A significant correlation was observed between FMD and plasma CoQ10 level (r = 0.727, P < 0.001). After adjusting for potential parameters, a stepwise multivariate linear regression analysis revealed that CoQ10 level was an independent predictor of FMD (ß = 0.018, P < 0.001). When CoQ10 was dichotomized using the median value (639.74 ng/mL), the conclusion remained unchanged (ß = 0.584, P < 0.001). Pearson's correlation analyses revealed that plasma CoQ10 level was negatively correlated with MDA (r = -0.48, P < 0.001) and 8-OHdG (r = -0.43, P < 0.001) levels. CONCLUSION: Our data demonstrate that impaired brachial artery FMD was common in HD patients. CoQ10 level was independently associated with FMD, and oxidative stress may constitute a link between CoQ10 level and endothelial dysfunction in these patients.

Effects of coenzyme Q10 on endothelial and cardiac function in patients undergoing haemodialysis: study protocol for a pilot randomised controlled trial.

INTRODUCTION: Endothelial and cardiac dysfunction are highly prevalent and are associated with cardiovascular morbidity and mortality among patients undergoing dialysis. For patients undergoing dialysis, no study has explored the effect of supplementation of coenzyme Q10 (CoQ10) on endothelial function. To our best of knowledge, only two small sample studies focused on the efficacy of supplementation of CoQ10 on cardiac function. However, the effect of CoQ10 supplementation on cardiac function remains uncertain in patients who undergo haemodialysis. The aim of this study is to explore whether CoQ10 supplementation can improve endothelial and cardiac function in patients undergoing haemodialysis. METHODS AND ANALYSIS: This is a pilot randomised controlled study. Eligible patients undergoing haemodialysis in our haemodialysis centre will be randomly allocated to the CoQ10 and control groups. The follow-up time is 12 months. The primary outcome is to assess the change of brachial artery endothelial-dependent flow-mediated dilation, left ventricular systolic function, diastolic function and Myocardial Performance Index at 12 months from baseline. Secondary outcomes are death or hospitalisation due to cardiovascular events, all-cause mortality, change of CoQ10 concentration, the ratio of ubiquinol to ubiquinone, the change of oxidative stress markers (including malondialdehyde and 8-hydroxy-deoxyguanosine) and Left Ventricular Mass Index. ETHICS AND DISSEMINATION: Risks associated with CoQ10 are minor, even at doses as high as 1800 mg according to previous studies. The trial has received ethics approval from the Medical Ethics Committee for Clinical Trials of Drugs, the 306th Hospital of Chinese PLA. The results of the study are expected to be published in a peer-reviewed journal and presented at academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900022258.