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Proteins in Jumonji family function as histone demethylases and participate in cardiac development. Jumonji domain containing 5 (JMJD5) is responsible for the embryonic development through removing methyl moieties from H3K36me2 histone, and has pro‐proliferative effect on heart and eye development. However, the protective role of JMJD5 against oxygen–glucose deprivation and reperfusion (OGD/R)‐induced injury in cardiomyocytes has not been fully understood. Firstly, myocardial ischemia/reperfusion (I/R) rat model was established by ligation of left coronary artery. OGD/R was performed in non‐transfected H9C2 or H9C2 transfected with pcDNA‐JMJD5 plasmid to induce cell cytotoxicity. Data from qRT‐PCR and western blot showed that JMJD5 was reduced in the heart tissues of myocardial I/R rat model and OGD/R‐induced H9C2. Secondly, JMJD5 over‐expression attenuated OGD/R‐induced decrease in cell viability and increase in lactate dehydrogenase secretion and cell apoptosis in H9C2. Mitophagy was promoted by pcDNA‐mediated over‐expression of JMJD5 with enhanced protein expression of LC3‐I, LC3‐II, Atg5, and Beclin 1. Thirdly, knockdown of JMJD5 aggravated OGD/R‐induced decrease in hypoxia‐inducible factor‐1α (HIF‐1α), whereas JMJD5 over‐expression enhanced BNIP3 (Bcl‐2/adenovirus E1B 19‐kDa interacting protein) through upregulation of HIF‐1α. Lastly, BNIP3 silencing promoted cell apoptosis, suppressed mitophagy, and attenuated the protective effects of JMJD5 over‐expression against OGD/R‐induced injury in H9C2. In conclusion, JMJD5 exerted protective effects against OGD/R‐induced injury in cardiomyocytes through upregulation of HIF‐1α‐BNIP3. [ABSTRACT FROM AUTHOR]

Background: Spontaneous hypertension is a leading risk factor for cardiovascular diseases morbidity and mortality. Glycine betaine (GB) is a natural vitamin that has the potential to lower blood pressure. This work attempted to investigate the role and mechanisms of GB in spontaneous hypertension., Methods: Spontaneously hypertensive rats (SHRs) were administrated with 100, 200, or 400 mg/kg of GB by gavage or combined with by injection of lentivirus-mediated STIM1 overexpression vector. The heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart weight/body weight (HW/BW) of rats were monitored. The pathological changes in myocardium were examined by hematoxylin and eosin staining and Masson staining. The expression of genes and proteins was detected by quantitative real-time PCR, western blotting, and immunohistochemistry., Results: GB at 200 and 400 mg/kg reduced the HR, SBP, DBP and HW/BW in SHRs. GB decreased the cross-sectional area and fibrotic area in the myocardium and downregulated the expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC) in the myocardium of SHRs. It indicated that GB treatment effectively alleviated myocardial hypertrophy in SHRs. Additionally, GB treatment repressed the expression of stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1) in the myocardium of SHRs. STIM1 overexpression reversed GB treatment-mediated inhibition of myocardial hypertrophy in SHRs., Conclusions: In conclusion, GB repressed STIM1/Orai1 signaling pathway, which contributed to alleviating myocardial hypertrophy in SHRs. Thus, our study provides a theoretical basis for GB as an antihypertensive drug., Competing Interests: None to declare., (Copyright 2023, Xiao et al.)

Objective: To observe whether there are some differences between myocardial postconditioning and remote postconditioning, and whether there is additional cardiac protection when they are used combined during myocardial ischemia/reperfusion injury in rabbits., Methods: Thirty healthy New Zealand rabbits which were randomly divided into 5 groups (n = 5): ischemic control group (CON), sham operation group (Sham), myocardial postconditioning group (MPostC), remote postconditioning group (RPostC), myocardial postconditioning plus remote postconditioning group (MPostC + RPostC). Acute myocardial infarction was induced by 45 minutes occlusion on left circumflex coronary artery (LCX) and 2 hours reperfusion in all anesthetized open-chest rabbits except the Sham, the coronary occlusion and reperfusion were determined by changes of ECG and cardiac color. Skeletal muscle ischemia model was induced by extrinsic iliac arteries occlusion and reperfusion with artery clamps. The condition that the extrinsic iliac arteries were occluded or reperfused could be tested by according to the distal arterial pulse. Plasma creatine kinase (CPK) activity and lactate dehydrogenase (LDH) activity were measured at baseline, the end of ischemia, after 1 hour and 2 hours of reperfusion respectively. The extent of myocardial infarction was assessed by triphenyltetrazolium (TTC) staining and measured by area ratio of AN/AAR., Results: Compared with the Con, myocardial infarct size was significantly reduced in MPostC and RpostC group (P < 0.05). But there was no significant difference between MPostC and RPostC group. Combined MPostC and RPostC markedly enhanced myocardial protection (P < 0.05). The trend of CPK and LDH release was similar to the trend of myocardial infarct size., Conclusion: Both MPostC and RPostC induced cardiac protection. There was no significant difference between MPostC and RPostC. Combined MPostC and RPostC induced markedly additive effect on myocardial protection.

Objective: To investigate the effects of rabbit limbs ischemia/reperfusion on myocardial necrosis and apoptosis in vivo., Methods: Thirty-six healthy new zealand rabbits were randomly divided into 3 groups: (1) Sham group; (2) I/R(Ischemia/reperfusion) group; (3) RPostC (remote postconditioning) group. The activity of blood serum creatine kinase (CK) and lactate dehydrogenase (LDH) were measured at baseline, the end of ischemia after 60 min and 120 min of reperfusion respectively. The extent of myocardial ischemia and the scope of myocardial infarction were assessed by evans blue and Triphenyl tetrazolium chloride (TTC). The myocardial cell's apoptosis at the area of myocardial ischemia was estimated by Tunel. Protein expression of caspase-3, Bcl-2 and Bax in myocardial ischemic area were analyzed with the method of immunohistochemistry., Results: Compared with I/R group, the myocardial infarct size and the CK activity were significantly reduced in RPostC group. The Tunel positive index of RPostC group in ischemic myocardium was significantly lower than that in I/R group (21.79% +/- 1.07% vs 35.81% +/- 1.10%, P < 0.05). Caspase-3 positive cells index was calculated with randomly selected five regions in each slide and then the positive cells in per hundred cells were calculated. The RPostC group of caspase-3 positive cells was significantly lower than that in I/ R group(25.03% +/- 1.16% as 39% +/- 2.43%, P < 0.05). Compared with the sham group, the Bax protein expression index and the Bcl-2 protein expression index of I/R group and RPostC group were increased. The Bax/Bcl-2 ratio of RPostC group decreased, while it was increased in I/R. Compared with the I/R group, the Bax protein expression and Bax/Bcl-2 ratio of RPostC group significantly reduced, but the expression index of Bcl-2 ratio was significantly increased, the differences were statistically significant., Conclusion: Limbs ischemia/postconditioning could significantly reduce necrosis and apoptosis of ischemia/reperfusion myocardium. The mechanism of reducing the myocardial cell apoptosis may have relation to inhibiting the activation of pro-apoptotic gene caspase-3 and increased expression of Bcl-2.

Objective: In this study, we try to find the better protocol of limb ischemia postconditioning by observing different protective effects of limb ischemic postconditioning (different strength and time windows in rabbits)., Methods: 42 healthy New Zealand rabbits were randomly divided into 7 groups (n = 6): Sham; Control (CON); Skeletal muscle postconditioning (SP); 6 min-delayed skeletal muscle postconditioning (6M-DSP); 1 min-delayed skeletal muscle postconditioning (1M-DSP); Strengthen skeletal muscle postconditioning (SSP); Weakened skeletal muscle postconditioning (WSP). Acute ischemia/reperfusion (I/R) model was induced by 45 minutes occlusion on left circumflex coronary artery (LCX) and 2 hours reperfusion in all anesthetized open-chest rabbits except the Sham. Limb ischemia was induced by external iliac arteries occlusion and reperfusion through artery clamps. The extent of myocardial infarction was assessed by triphenyltetrazolium (TTC) staining. Blood serum creatine kinase (CK) activity and lactate dehydrogenase (LDH) activity were measured at baseline,the end of ischemia, after 1 hour and 2 hours of reperfusion respectively., Results: Compared with the CON, the weight ratio and area ratio of myocardial infarction size were significantly decreased by 49.97% and 43.78% in SP, by 42.32% and 42.68% in 1M-DSP, by 48.36% and 48.86% in SSP (P < 0.05). But there was no significant difference between SP and 1M-DSP and SSP (P > 0.05). Otherwise, compared with the CON, myocardial infarct size was not significantly reduced in 6M-DSP or WSP (P > 0.05). The change of CK was similar to the trend of myocardial infarct size., Conclusion: The limb ischemia strength of 5 mini/1 minR x 1 cycle could significantly reduce the myocardial ischemia/ reperfusion injury in rabbits, if it was achieved before myocardial reperfusion.