Deleterious effect in endothelin receptor-mediated coronary artery smooth muscle contractility in high-salt diet rats.

BACKGROUND AND AIMS: High-salt diet has been suggested to increase the risk of heart disease. However, the mechanisms underlying coronary artery tension dysfunction caused by high-salt diet are unclear. Previous studies have shown that coronary artery spasm is often induced by endothelin-1 (ET-1) and thromboxane, leading to myocardial ischemia, while the store-operated Ca2+ entry (SOCE) function of coronary smooth muscle is very important in this process. METHODS AND RESULTS: Tension measurements of endothelium-denuded coronary artery ring segments showed that vasocontraction induced by U46619, ET-1, orSTIM1/Orai1-mediated SOCE was significantly lower in 4% high-salt diet rats than in control rats fed a regular diet. The results of western blotting and immunohistochemistry assays showed lower expression levels of endothelial receptors ETA and ETB, STIM1 and Orai1 in coronary artery of high-salt intake rats compared with control rats. Fibrosis was observed by using Masson's trichrome staining and picrosirius red staining. The plasma ET-1 concentration in high-salt diet rats was significantly higher than that of controls. The interventricular septum and posterior wall of high-salt diet rats were significantly thickened. CONCLUSION: Our findings indicated that coronary artery tension was significantly decreased in 4% high-salt diet rats and that this decrease may be due to the change of endothelin receptor and its downstream pathway SOCE related protein expression in coronary artery. Coronary fibrosis was observed in rats fed with high-salt diet. This study provides potential mechanistic insights into high-salt intake-induced heart disease.

Normal Values of Magnetic Resonance T1ρ Relaxation Times in the Adult Heart at 1.5 T MRI.

BACKGROUND: T1ρ mapping is a new quantitative MRI technique in recent years. In order to use T1ρ mapping as a noncontrast method to assess myocardial fibrosis, it is necessary to establish a range of normal values. PURPOSE: To establish a potential normal range of cardiac T1ρ values in healthy adults and to explore the influence of slice location and gender on T1ρ values. STUDY TYPE: Prospective. POPULATION: A total of 57 healthy volunteers without cardiovascular risk factors (age 26.7 ± 11.8 years; 29 males). FIELD STRENGTH/SEQUENCE: 1.5 T; modified Look-Locker inversion recovery (MOLLI) (T1 mapping), multiecho gradient-spin-echo (GraSE) (T2 mapping) and T1ρ -prepared steady-state free precession (T1ρ mapping) sequences. ASSESSMENT: Basal, mid, and apical short-axis left ventricular T1 , T2 , and T1ρ maps were acquired. T1ρ maps at spin-locking frequencies of 5 and 400 Hz were subtracted to create myocardial fibrosis index (mFI) maps. Slice-average and global average T1 , T2 , T1ρ , and mFI values were determined. STATISTICAL TESTS: Shapiro-Wilk test, Independent t-test, ANOVA test, Pearson correlation coefficient (r). SIGNIFICANCE: P value < 0.05. RESULTS: The global average values of T1 , T2 , T1ρ, and mFI were 1053 ± 34 msec, 51.9 ± 2.3 msec, 47.9 ± 2.8 msec, and 4.4 ± 1.6 msec. T1ρ values showed a significant gradual increase from the basal slice to the apical slice of the heart (basal 46.5 ± 2.7 msec, mid 48.0 ± 2.9 msec, apical 49.2 ± 3.3 msec). The T1ρ and mFI values of females (49.7 ± 2.4 msec and 5.1 ± 1.2 msec, respectively) were significantly higher than those of males (46.2 ± 1.9 msec and 3.7 ± 1.7 msec, respectively). In addition, there was a moderate positive correlation between global T1ρ values and global T1 values (r = 0.44, P < 0.05) and a moderate positive correlation between global T1ρ values and global T2 values (r = 0.42, P < 0.05). DATA CONCLUSION: In this study, the global T1ρ values of healthy adults' hearts were 47.9 ± 2.8 msec. This study found that gender and slice location of myocardium can affect the T1ρ values. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

Association of the P441L KCNQ1 variant with severity of long QT syndrome and risk of cardiac events.

Dysfunction of potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is a primary cause of long QT syndrome type 1 (LQT1). Here, we report a missense mutation P441L in KCNQ1 C-terminus of a 37-year-old woman with severe LQT1 phenotype. Variant P441L transporting to the plasma membrane and interacting with KCNE1 were both markedly decreased, leading to potassium efflux disorder and eventually LQT1. Mutations between the C-terminal helix A and helix B of KCNQ1 have linked with low cardiac event risk, however, we firstly find variant P441L causing a severe LQT1 phenotype with a high risk of cardiac events.

Britanin relieves ferroptosis-mediated myocardial ischaemia/reperfusion damage by upregulating GPX4 through activation of AMPK/GSK3ß/Nrf2 signalling.

CONTEXT: Ferroptosis was described as an important contributor to the myocardial ischaemia/reperfusion (MIR) injury, and britanin (Bri) was reported to exert antitumor and anti-inflammatory activities. OBJECTIVE: Our study explores the effect and mechanism of Bri on MIR damage. MATERIALS AND METHODS: The rat model of MIR was established by ligation of the left anterior descending coronary artery. Male Sprague-Dawley (SD) rats were divided into three groups: sham group (n = 6), MIR group (n = 6) and MIR + Bri group (n = 6; 50 mg/kg). Rats were intragastrically pre-treated with Bri or normal saline once daily for 3 days. To further verify the role and mechanism of Bri, H9C2 cells were subjected to hypoxia plus reoxygenation (H/R) to induce the in vitro model of MIR. RESULTS: Compared with MIR rats, Bri significantly decreased infarct area (22.50% vs. 38.67%), myocardial apoptosis (23.00% vs. 41.5%), creatine phosphokinase (0.57 U/mL vs. 0.76 U/mL), and lactate dehydrogenase levels (3.18 U/mL vs. 5.17 U/mL), concomitant with alleviation of ferroptosis. Mechanistically, Bri treatment induced the activation of the adenosine monophosphate activated protein kinase (AMPK)/glycogen synthase kinase 3ß (GSK3ß)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in vivo. In addition, the AMPK/GSK3ß/Nrf2 pathway participated in the regulation of glutathione peroxidase 4 (GPX4) expression, and silencing of Nrf2 attenuated the effect of Bri on H/R-induced cell injury. DISCUSSION AND CONCLUSIONS: Bri protected against ferroptosis-mediated MIR damage by upregulating GPX4 through activation of the AMPK/GSK3ß/Nrf2 signalling, suggesting that Bri might become a novel therapeutic agent for MIR.