Preventive Effects of Vanillic Acid on Lipids, Bax, Bcl-2 and Myocardial Infarct Size on Isoproterenol-Induced Myocardial Infarcted Rats: A Biochemical and In Vitro Study

2010 ◽  
Vol 11 (1) ◽  
pp. 58-66 ◽  
Author(s):  
P. Stanely Mainzen Prince ◽  
K. Dhanasekar ◽  
S. Rajakumar
Keyword(s):  
Infarct Size ◽  
Vanillic Acid ◽  
Myocardial Infarct ◽  
In Vitro Study ◽  
Vitro Study ◽  
Myocardial Infarct Size ◽  
Preventive Effects

scholarly journals Overexpression of SERCA2a Alleviates Cardiac Microvascular Ischemic Injury by Suppressing Mfn2-Mediated ER/Mitochondrial Calcium Tethering

2021 ◽  
Vol 9 ◽  
Author(s):  
Feng Tian ◽  
Ying Zhang
Keyword(s):  
Endoplasmic Reticulum ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemic Injury ◽  
Calcium Overload ◽  
Mitochondrial Calcium ◽  
Myocardial Infarct Size ◽  
Hypoxic Injury

Our previous research has shown that type-2a Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) undergoes posttranscriptional oxidative modifications in cardiac microvascular endothelial cells (CMECs) in the context of excessive cardiac oxidative injury. However, whether SERCA2a inactivity induces cytosolic Ca2+ imbalance in mitochondrial homeostasis is far from clear. Mitofusin2 (Mfn2) is well known as an important protein involved in endoplasmic reticulum (ER)/mitochondrial Ca2+ tethering and the regulation of mitochondrial quality. Therefore, the aim of our study was to elucidate the specific mechanism of SERCA2a-mediated Ca2+ overload in the mitochondria via Mfn2 tethering and the survival rate of the heart under conditions of cardiac microvascular ischemic injury. In vitro, CMECs extracted from mice were subjected to 6 h of hypoxic injury to mimic ischemic heart injury. C57-WT and Mfn2KO mice were subjected to a 1 h ischemia procedure via ligation of the left anterior descending branch to establish an in vivo cardiac ischemic injury model. TTC staining, immunohistochemistry and echocardiography were used to assess the myocardial infarct size, microvascular damage, and heart function. In vitro, ischemic injury induced irreversible oxidative modification of SERCA2a, including sulfonylation at cysteine 674 and nitration at tyrosine 294/295, and inactivation of SERCA2a, which initiated calcium overload. In addition, ischemic injury-triggered [Ca2+]c overload and subsequent [Ca2+]m overload led to mPTP opening and ΔΨm dissipation compared with the control. Furthermore, ablation of Mfn2 alleviated SERCA2a-induced mitochondrial calcium overload and subsequent mito-apoptosis in the context of CMEC hypoxic injury. In vivo, compared with that in wild-type mice, the myocardial infarct size in Mfn2KO mice was significantly decreased. In addition, the findings revealed that Mfn2KO mice had better heart contractile function, decreased myocardial infarction indicators, and improved mitochondrial morphology. Taken together, the results of our study suggested that SERCA2a-dependent [Ca2+]c overload led to mitochondrial dysfunction and activation of Mfn2-mediated [Ca2+]m overload. Overexpression of SERCA2a or ablation of Mfn2 expression mitigated mitochondrial morphological and functional damage by modifying the SERCA2a/Ca2+-Mfn2 pathway. Overall, these pathways are promising therapeutic targets for acute cardiac microvascular ischemic injury.

scholarly journals Nod-like Receptor Protein 3 (Nlrp3) Inflammasomes Inhibition by Metformin Limits Myocardial Ischemia/reperfusion Injury

2020 ◽  
Author(s):  
Jing Zhang ◽  
Liu Yang ◽  
Qin Zhang ◽  
Xing Shi ◽  
Fuzhou Hua ◽  
...  
Keyword(s):  
Infarct Size ◽  
Nlrp3 Inflammasome ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Inflammasome Activation ◽  
Myocardial Infarct Size ◽  
Ampk Phosphorylation ◽  
Nlrp3 Inflammasome Activation ◽  
Cardioprotective Effects

Abstract Background Ischemia/reperfusion (I/R) injury is a life-threatening vascular emergency following myocardial infarction. Our previous study showed cardioprotective effects of metformin against myocardial I/R injury. In this study, we further examined the involvement of AMPK mediated activation of NLRP3 inflammasome in this cardioprotective effect of metformin. Methods Myocardial I/R injury was simulated in a rat heart Langendorff model and neonatal rat ventricle myocytes (NRVMs) were subjected to hypoxi/reoxygenation (H/R) to establish an in vitro model. Outcome measures included myocardial infarct size, hemodynamic monitoring, myocardial tissue injury, myocardial apoptotic index and the inflammatory response. myocardial infarct size and cardiac enzyme activities. Results First, we found that metformin postconditioning can not only significantly alleviated myocardial infarct size, attenuated cell apoptosis, and inhibited myocardial fibrosis. Furthermore, metformin activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and decreased NLRP3 inflammasome activation. In isolated NRVMs metformin increased cellular viability, decreased LDH activity and inhibited cellular apoptosis and inflammation. Importantly, inhibition of AMPK phosphorylation by Compound C (CC) resulted in decreased survival of cardiomyocytes mainly by inducing the release of inflammatory cytokines and increasing NLRP3 inflammasome activation. Finally, in vitro studies revealed that the NLRP3 activator nigericin abolished the anti-inflammatory effects of metformin in NRVMs, but it had little effect on AMPK phosphorylation. Conclusions Collectively, our study confirmed that metformin exerts cardioprotective effects by regulating myocardial I/R injury-induced inflammatory response, which was largely dependent on the enhancement of the AMPK pathway, thereby suppressing NLRP3 inflammasome activation.

scholarly journals Therapeutic Effect of Local Injection of VX765 Sodium Alginate Nanogel on Myocardial Infarction

2021 ◽  
Author(s):  
Qingxin Tian ◽  
Jianlong Liu ◽  
Qin Chen ◽  
Mingxiao Zhang
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Infarct Size ◽  
Sodium Alginate ◽  
Cardiac Fibrosis ◽  
Myocardial Infarct ◽  
Morphological Observation ◽  
Myocardial Infarct Size ◽  
Sprague Dawley

Abstract Objectives: To determine the effect of polyethyleneimine/sodium alginate composite nano-gel (AG/PEI-VX765NGs) coated with VX765 on cardiac function in rats with myocardial infarction (MI). Methods: VX765-polyethyleneimine nano-microspheres (PEI-VX765 NP) were encapsulated by sodium alginate (AG) nanogel (NGs) to construct AG/PEI-VX765 NGs. The morphological observation was performed under scanning electron microscope (SEM). The viability was evaluated by using CCK-8 assay in vitro. Then, 24 male SPF Sprague-Dawley rats were randomly divided into 4 groups: Sham, MI, PEI-VX765NP, and AG/PEI-VX765NGs. After 28 days, rats in each group were subjected to assessment of cardiac function by echocardiography. The myocardial infarct size was evaluated by TTC test, and the differences in cardiac fibrosis and cardiomyocyte apoptosis between groups were analyzed by histological methods. Results: The prepared NGs shows a porous structure, while PEI-VX765 NP is uniformly distributed in the AG NGs samples. AG/PEI-VX765 NGs with a concentration of VX765 (range: 0-1000 μM) displayed no significant toxicity to cells. Meanwhile, we observed a relatively more persistent release of VX765 from AG/PEI-VX765 NGs compared with PEI-VX765. LVIDs and LVIDd in both PEI-VX765 and AG/PEI-VX765NGs groups were significantly smaller than those in MI group, while ejection fraction (EF) and short-axis shortening rate (FS) were markedly increased in the above-mentioned two groups. Compared with MI group, PEI-VX765 and AG/PEI-VX765NGs groups exhibited a significant reduction in the infarct size, degree of fibrosis, and the rate of TUNEL positive cells. Conclusion: AG/PEI-VX765NGs can significantly improve the cardiac function of rats with MI.

Preventive effects of iontophoresis on bovine enamel decalcification through enhancing uptake and transportation of fluoride - in vitro study

2018 ◽  
Vol 28 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Toshiko Tanaka ◽  
Ayaka Saito ◽  
Koji Watanabe ◽  
Katsura Saeki ◽  
Hideaki Nakashima ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Vitro Study ◽  
Bovine Enamel ◽  
Preventive Effects

Sex differences in myocardial infarct size are abolished by sarcolemmal KATP channel blockade in rat

2006 ◽  
Vol 290 (6) ◽  
pp. H2644-H2647 ◽  
Author(s):  
Micah S. Johnson ◽  
Russell L. Moore ◽  
David A. Brown
Keyword(s):  
At Risk ◽  
Sex Differences ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Female Rats ◽  
Male Rats ◽  
Myocardial Infarct Size ◽  
Sprague Dawley

This study was conducted to examine the relationship between myocardial ATP-sensitive potassium (KATP) channels and sex differences in myocardial infarct size after in vitro ischemia-reperfusion (I/R). Hearts from adult male and female Sprague-Dawley rats were excised and exposed to an I/R protocol (1 h of ischemia, followed by 2 h of reperfusion) on a modified Langendorff apparatus. Hearts from female rats showed significantly smaller infarct sizes than hearts from males (23 ± 4 vs. 40 ± 5% of the zone at risk, respectively; P < 0.05). Administration of HMR-1098, a sarcolemmal KATP channel blocker, abolished the sex difference in infarct size (42 ± 4 vs. 45 ± 5% of the zone at risk in hearts from female and male rats, respectively; P = not significant). Further experiments showed that blocking the KATP channels in ischemia, and not reperfusion, was sufficient to increase infarct size in female rats. These data demonstrate that sarcolemmal KATP channels are centrally involved in mechanisms that underlie sex differences in the susceptibility of the intact heart to I/R injury.

scholarly journals Luteolin Modulates SERCA2a Leading to Attenuation of Myocardial Ischemia/ Reperfusion Injury via Sumoylation at Lysine 585 in Mice

2018 ◽  
Vol 45 (3) ◽  
pp. 883-898 ◽  
Author(s):  
Yinping Du ◽  
Ping Liu ◽  
Tongda Xu ◽  
Defeng Pan ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background/Aims: The myocardial sarcoplasmic reticulum calcium ATPase (SERCA2a) is a pivotal pump responsible for calcium cycling in cardiomyocytes. The present study investigated the effect of luteolin (Lut) on restoring SERCA2a protein level and stability reduced by myocardial ischemia/reperfusion (I/R) injury. We verified a hypothesis that Lut protected against myocardial I/R injury by regulating SERCA2a SUMOylation. Methods: The hemodynamic data, myocardial infarct size of intact hearts, apoptotic analysis, mitochondrial membrane potential (ΔΨm), the level of SERCA2a SUMOylation, and the activity and expression of SERCA2a were examined in vivo and in vitro to clarify the cardioprotective effects of Lut after SUMO1 was knocked down or over-expressed. The putative SUMO conjugation sites in mouse SERCA2a were investigated as the possible regulatory mechanism of Lut. Results: Initially, we found that Lut reversed the SUMOylation and stability of SERCA2a as well as the expression of SUMO1, which were reduced by I/R injury in vitro. Furthermore, Lut increased the expression and activity of SERCA2a partly through SUMO1, thus improving ΔΨm and reducing apoptotic cells in vitro and promoting the recovery of heart function and reducing infarct size in vivo. We also demonstrated that SUMO acceptor sites in mouse SERCA2a involving lysine 585, 480 and 571. Among the three acceptor sites, Lut enhanced SERCA2a stability via lysine 585. Conclusions: Our results suggest that Lut regulates SERCA2a through SUMOylation at lysine 585 to attenuate myocardial I/R injury.

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