Astaxanthin Alleviates the Process of Cardiac Hypertrophy by Targeting the METTL3/Circ_0078450/MiR-338-3p/GATA4 Pathway.

Astaxanthin (ASX) is a natural antioxidant with preventive and therapeutic effects on various human diseases. However, the role of ASX in cardiac hypertrophy and its underlying molecular mechanisms remain unclear.Cardiomyocytes (AC16) were used with angiotensin-II (Ang-II) to mimic the cardiac hypertrophy cell model. The protein levels of hypertrophy genes, GATA4, and methyltransferase-like 3 (METTL3) were determined by western blot analysis. Cell size was assessed using immunofluorescence staining. The expression of circ_0078450, miR-338-3p, and GATA4 were analyzed by quantitative real-time PCR. Also, the interaction between miR-338-3p and circ_0078450 or GATA4 was confirmed by dual-luciferase reporter and RIP assays, and the regulation of METTL3 on circ_0078450 was verified by MeRIP and RIP assays.ASX reduced the hypertrophy gene protein expression and cell size in Ang-II-induced AC16 cells. Circ_0078450 was promoted under Ang-II treatment, and ASX reduced circ_0078450 expression in Ang-II-induced AC16 cells. Circ_0078450 could sponge miR-338-3p to positively regulate GATA4 expression, and GATA4 overexpression overturned the suppressive effect of circ_0078450 knockdown on Ang-II-induced cardiomyocyte hypertrophy. Also, the inhibitory effect of ASX on Ang-II-induced cardiomyocyte hypertrophy could be reversed by circ_0078450 or GATA4 overexpression. In addition, METTL3 mediated the m6A methylation of circ_0078450 to enhance circ_0078450 expression. Moreover, METTL3 knockdown suppressed Ang-II-induced cardiomyocyte hypertrophy by inhibiting circ_0078450 expression.Our data showed that ASX repressed cardiac hypertrophy by regulating the METTL3/circ_0078450/miR-338-3p/GATA4 axis.

Intravenous insulin preparation administration for myocardial viability 18F-FDG imaging has the potential to reduce radiation exposure dose.

OBJECTIVE: Fluorine-18-fluorodeoxyglucose (18F-FDG) injection activity is positively associated with radiation dose and positron emission tomography (PET) image count. Measurement error is greater with smaller counts; therefore, precise analysis is needed to avoid high doses of radiation exposure caused by high 18F-FDG injection. We aimed to identify and validate the optimal 18F-FDG injection activity and acquisition time for cardiac viability imaging with intravenous insulin preparation administration based on fixed 18F-FDG activity. MATERIALS AND METHODS: Cardiac PET images from 30 patients with coronary artery disease (CAD) were retrospectively reconstructed into different durations. An optimal product of the maximum standardized uptake value (SUV) of the myocardium, and segmental uptake (SU), and acquisition time (MSAT) was determined through a receiver operating characteristic curve. RESULTS: The optimal acquisition time (OAT) was equal to MSAT divided by mean SUV of the myocardium (MyoSUV) and was validated in another 26 patients with CAD. The optimal MSAT was 848.2s. In the validation group, the OAT was 129±76s (95% confidence interval, 99-160s), approximately one-third of the usual acquisition time. The MyoSUV and SU were equivalent between PET image duration of OAT and 600s (7.71±3.01 vs. 7.56±2.94; 67.1±15.4% vs. 67.7±15.6%). CONCLUSION: Intravenous insulin preparation administration has the potential to decrease the radiation exposure or acquisition time in cardiac viability 18F-FDG imaging to one-third, without losing the accurate measurement of MyoSUV or SU when reaching an OAT.

Elevated standardised uptake value of the free wall of the right ventricular myocardium is correlated with enlarged left ventricular end-diastolic volume among patients with heart failure with reduced ejection fraction: A retrospective study.

This study aimed to investigate the relationship between the standardised uptake value of the free wall of the right ventricular myocardium (SUVrv) and left ventricular end-diastolic volume (LVEDV) among patients with heart failure with reduced ejection fraction (HFrEF) with coronary artery disease (CAD). This retrospective study included 50 patients with CAD and HFrEF scheduled for cardiac viability imaging with electrocardiography-gated fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). The maximal SUVrv was measured. The LVEDV and left ventricular ejection fraction (LVEF) were automatically measured using quantitative gated single-photon emission computed tomography. Plasma brain natriuretic peptide (BNP) levels were obtained from medical records.The LVEF (0.24±0.06) was markedly reduced while the LVEDV (201.5±59.9mL) and BNP level (1348.1±1382.9pg/mL) were remarkably elevated. The SUVrv was 3.7±1.7 and was similar between patients with and without diabetes. The SUVrv was significantly positively correlated with the LVEDV and BNP level (r=0.35, 0.45; P=0.01, ≤0.01, respectively) but was unrelated to the LVEF (r=0.11, P=0.44). Herein, SUVrv was elevated and significantly positively correlated with LVEDV and BNP levels among patients with CAD and HFrEF but was unrelated to LVEF and diabetic status.

CYP2C19 metabolizer phenotypes may affect the efficacy of statins on lowering small dense low-density lipoprotein cholesterol of patients with coronary artery disease.

Background: Dyslipidemia is a major cause of arteriosclerotic cardiovascular disease (ASCVD), and low-density lipoprotein cholesterol (LDL-C) is the profile to be reduced to prevent disease progression. Small dense low-density lipoprotein cholesterol (sdLDL-C) has been proven to be a more effective biomarker than LDL-C for ASCVD primary and secondary prevention. CYP2C19 is an important drug metabolism gene. This study aimed to investigate the relationship between sdLDL-C and coronary artery disease (CAD) risk factors and explore the influence of CYP2C19 metabolizer phenotypes on the sdLDL-C lowering efficacy of statins. Methods: This study recruited 182 patients with CAD and 200 non-CAD controls. Baseline laboratory indices of fasting blood were detected, including blood lipids, glucose, and creatinine. In addition, LDL-C subfractions were separated and quantified. Gene polymorphisms of SLCO1B1 and CYP2C19 were detected in patients with CAD. The LDL-C subfractions levels of patients with CAD were followed up after statin drug treatment. Results: Total cholesterol, LDL-C, LDLC-2, LDLC-3, LDLC-4, LDLC-5, LDLC-6, LDLC-7, and sdLDL-C levels of patients with CAD were significantly higher than those in non-CAD controls. Meanwhile, sdLDL-C (AUC = 0.838) and LDLC-4 (AUC = 0.835) performed outstandingly in distinguishing patients with CAD from controls. Based on CYP2C19 metabolizer phenotypes, 113 patients with CAD were divided into the extensive metabolizer (EM, n = 49), intermediate metabolizer (IM, n = 52), and poor metabolizer (PM, n = 12) groups. The patients with IM and PM metabolizer phenotypes had better sdLDL-C lowering efficacy after taking statin drugs than patients with EM phenotype (P = 0.0268, FDR = 0.0536). The SLCO1B1 genotype had no significant impact on the efficacy of statins (P = 0.1611, FDR = 0.1611). Conclusion: sdLDL-C and LDLC-4 outperformed other blood lipids such as LDL-C for CAD risk screening. CYP2C19 metabolizer phenotypes had the potential to predict the efficacy of statins in lowering sdLDL-C.

Mechanism of Isosorbide Dinitrate Combined with Exercise Training Rehabilitation to Mobilize Endothelial Progenitor Cells in Patients with Coronary Heart Disease.

it was to explore effect of isosorbide dinitrate combined with exercise training and rehabilitation on endothelial progenitor cells (EPCs) in coronary heart disease. EPCs were isolated and cultured from peripheral blood of coronary heart disease patients, and morphology and surface markers were detected. Then, 116 patients were rolled into treatment group (isosorbide dinitrate + exercise rehabilitation training) and control group (isosorbide dinitrate). Characteristics of EPCs cells after treatment were compared. The mononuclear cells were round and small in size and were not evenly distributed in the culture plate. EPCs cells grew as colonies after 8d-culture, and the surrounding cells grew outward in a germinating manner with colonies as the center, forming multiple cell populations. Positive rates of EPCs surface markers CD133, CD34, and vascular endothelial growth factor receptor (KDR) were 11.25±3.07%, 48.18±9.13%, and 76.36±8.27%, respectively. Proliferation activity of EPCs in the treatment group was dramatically higher versus controls at day three, five, and seven (P<0.05). Adhesion ability of EPCs in treatment group was dramatically higher than controls at day three, five, and seven (P<0.05). Migration ability of EPCs in treatment group was dramatically higher versus control group at day three, five, and seven (P<0.05). In short, isosorbide dinitrate plus exercise rehabilitation greatly enhanced the proliferation activity, adhesion ability, and migration ability of EPCs cells, which also played a beneficial role in the repair of endothelial injury, with notable effects.