Phosphorylation of CaMK and CREB-Mediated Cardiac Aldosterone Synthesis Induced by Arginine Vasopressin in Rats with Myocardial Infarction

Both aldosterone and arginine vasopressin (AVP) are produced in the heart and may participate in cardiac fibrosis. However, their relationship remains unknown. This study aims to demonstrate the regulation and role of AVP in aldosterone synthesis in the heart. Rats were subjected to a sham operation or myocardial infarction (MI) by ligating the coronary artery. Cardiac function and fibrosis were assessed using echocardiography and immunohistochemical staining, respectively. In addition, the effects of AVP stimulation on cardiac microvascular endothelial cells (CMECs) were studied using ELISA, real-time PCR, and Western blotting. Compared with the rats having undergone a sham operation, the MI rats had an increased LVMI, type I collagen composition, and concentrations of aldosterone and AVP in the heart but decreased cardiac function. As the MI rats aged, the LVMI, type I collagen, aldosterone, and AVP increased, while the LVMI decreased. Furthermore, AVP time-dependently induced aldosterone secretion and CYP11B2 mRNA expression in CMECs. The p-CREB levels were significantly increased by AVP. Nevertheless, these effects were completely blocked by SR49059 or partially inhibited by KN93. This study demonstrated that AVP could induce the secretion of local cardiac aldosterone, which may involve CaMK and CREB phosphorylation and CYP11B2 upregulation through V1 receptor activation

I Ks Protects from Ventricular Arrhythmia during Cardiac Ischemia and Reperfusion in Rabbits by Preserving the Repolarization Reserve

Introduction: The function of the repolarization reserve in the prevention of ventricular arrhythmias during cardiac ischemia/reperfusion and the impact of ischemia on slowly activated delayed rectifier potassium current (IKs) channel subunit expression are not well understood. Methods and Results: The responses of monophasic action potential duration (MAPD) prolongation and triangulation were investigated following an L-768,673-induced blockade of I Ks with or without ischemia/reperfusion in a rabbit model of lef

Associations of Renal Function Trajectories and Long‐Term Cardiovascular Risks Among a Population Without Chronic Kidney Disease

Background The longitudinal trajectories of renal function have been associated with cardiovascular events in patients with chronic kidney disease (CKD). However, the change pattern of renal function in those without CKD has not yet been reported. We aim to explore patterns of renal function change in a non‐CKD population and its associated risks with cardiovascular outcomes. Methods and Results The present study analyzed data from 4 prospective cohorts and was restricted to participants without baseline CKD. The primary outcome was major adverse cardiovascular events, defined as a composite of myocardial infarction, chronic heart failure, stroke, and cardiovascular deaths. We used a group‐based trajectory model to identify latent groups and analyzed the associated risk with Cox regression models. The complete dates of this study were June 1, 2020, through January 1, 2021. The final sample comprised 23 760 participants (mean age, 58.63 [9.12] years, 10 618 men, and 17 799 White participants). During 20.56 years follow‐up, 8328 (35.05%) first major adverse cardiovascular events happened. Four trajectories in estimated glomerular renal function and 3 patterns of CKD progression were identified. Compared with subjects assigned to class I trajectory (high to mildly decreased group), the adjusted hazard ratios of major adverse cardiovascular events for class II (normal to mildly decreased group), class III (normal to moderately decreased group), and class IV (mildly to severely decreased group) were 1.11 (95% CI, 1.01–1.23), 1.27 (95% CI, 1.14–1.40), and 1.56 (95% CI, 1.38–1.77), respectively. Likewise, participants assigned to the slow and rapid progression groups had elevated HRs for major adverse cardiovascular events (1.75 [95% CI, 1.39–2.21] and 2.19 [95% CI, 1.68–2.86], respectively) when compared with the stable group. Findings were generally consistent in stratification analysis, but significant interaction effects by age and smoking status were detected. Conclusions In this study, we identified unique trajectory groups for renal function. These findings may signal an underlying high‐risk population and inspire future studies on individualized risk management

Role of TRPM7 Channels in Hyperglycemia-Mediated Injury of Vascular Endothelial Cells

<div><p>This study investigated the change of transient receptor potential melastatin 7 (TRPM7) expression by high glucose and its role in hyperglycemia induced injury of vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were incubated in the presence or absence of high concentrations of D-glucose (HG) for 72h. RT-PCR, Real-time PCR, Western blotting, Immunofluorescence staining and whole-cell patch-clamp recordings showed that TRPM7 mRNA, TRPM7 protein expression and TRPM7-like currents were increased in HUVECs following exposure to HG. In contrast to D-glucose, exposure of HUVECs to high concentrations of L-glucose had no effect. HG increased reactive oxygen species (ROS) generation, cytotoxicity and decreased endothelial nitric oxide synthase protein expression, which could be attenuated by knockdown of TRPM7 with TRPM7 siRNA. The protective effect of silencing TRPM7 against HG induced endothelial injury was abolished by U0126, an inhibitor of the extracellular signal-regulated kinase signaling pathway. These observations suggest that TRPM7 channels play an important role in hyperglycemia-induced injury of vascular endothelial cells.</p> </div

Comparison of waveforms between the Sham (2-d) and Infarct (2-d) groups after bolus injection of epinephrine.

<p>The only morphological differences in peri-infarct MAP were identified in the Infarct (2-d) group. (<b>A</b>) ECG Lead II waveforms showing that both groups had a comparable degree of heart rate increase. (<b>B</b>) MAP recorded at the peri-infarct epicardial zone showing that after the adrenergic challenge, the MAP of the Infarct (2-d) group had a dramatic shortening of MAPD30, whereas the MAPD90 was only minimally changed. (<b>C</b>) Direct overlapping of MAP showing that the MAP of the Infarct (2-d) group demonstrates more prominent triangulation.</p

Study protocol 1 of experiments.

<p>Monophasic action potentials were recorded after the equilibration at both the middle of the infarct zone and the unaffected zone of the epicardium. For L-768,673, The infusion rate of the initial dose was 0.5 µg/kg/h for 30 min, and the maintenance rate was 0.25 µg/kg/h for two hours. MAP duration data were expressed as MAPD90/60/30_{Baseline, Initial Dose, I5, I10, I15, I20, R5, R10, R15, R20, R25, R30, R45, R60, R75, R90, R105, R120}, which stood for MAPD90/60/30 recorded at baseline, after initial dose, at ischemia for 5 min, 10 min, 15 min, 20 min and at reperfusion for 5 min, 10 min, 15 min, 20 min, 25 min, 30 min, 45 min, 60 min, 75 min, 90 min, 105 min, 120 min, respectively.</p

MAPDs, triangulations and MAP waveforms comparison between the IR+L-768,673 and IR+vehicle groups.

<p>(<b>A</b>) Epicardial MAPDs and triangulation recorded from the ischemia/reperfusion zone (apical) in the IR+L-768,673 group and the IR+vehicle group. Triangulations of the IR+L-768,673 group were increased compared with those of the IR+vehicle group by 31.1%, 26.5%, and 19.3% at R45, R60, and R75 respectively. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031545#s2" target="_blank">Results</a> are mean ± standard deviation (STD). * P<0.05 vs. IR+vehicle. (<b>B</b>) Comparison of monophasic action potential (MAP) waveforms between the IR+L-768,673 and IR+vehicle groups at R45, R60, and R75.</p

Epicardial MAPD90/60/30 and triangulation (MAPD90 - MAPD30) recorded from the remote zone (basal).

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031545#s2" target="_blank">Results</a> were means ± STD. There were no significant differences between groups.</p