Antiischemic effect of trimetazidine: Enzymatic and electric response in a model of in-vitro myocardial ischemia

1990 ◽  
Vol 4 (S4) ◽  
pp. 808-809 ◽  
Author(s):  
C. Libersa ◽  
E. Honor� ◽  
M. Adamantidis ◽  
E. Rouet ◽  
B. Dupuis
Keyword(s):  
Myocardial Ischemia ◽  
Electric Response ◽  
Antiischemic Effect

scholarly journals iPLA2β Contributes to ER Stress-Induced Apoptosis during Myocardial Ischemia/Reperfusion Injury

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1446
Author(s):  
Tingting Jin ◽  
Jun Lin ◽  
Yingchao Gong ◽  
Xukun Bi ◽  
Shasha Hu ◽  
...  
Keyword(s):  
Cell Death ◽  
Heart Disease ◽  
Myocardial Ischemia ◽  
Ischemic Heart Disease ◽  
Er Stress ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion ◽  
Induced Apoptosis

Both calcium-independent phospholipase A2 beta (iPLA2β) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2β is increased during myocardial ischemia/reperfusion (I/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2β in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I/R injury models are significantly elevated. Further, iPLA2β knockout mice and siRNA mediated iPLA2β knockdown are employed to evaluate the ER stress and cell apoptosis during I/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2β. Our data demonstrate the increase of iPLA2β augments ER stress and enhances cardiomyocyte apoptosis during I/R injury in vitro and in vivo. Inhibition of iPLA2β ameliorates ER stress and decreases cell death. Mechanistically, iPLA2β promotes ER stress and apoptosis by translocating to ER upon myocardial I/R injury. Together, our study suggests iPLA2β contributes to ER stress-induced apoptosis during myocardial I/R injury, which may serve as a potential therapeutic target against ischemic heart disease.

Study on the Effects of Kuanxiong Aerosol on the Isolated Artery and Rabbits Acute Myocardial Ischemia Model

2021 ◽  
Vol 24 ◽  
Author(s):  
Xia Liu ◽  
Feihua Huang ◽  
Xiao Lu ◽  
Yuji Wang ◽  
Tingting Cai ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Troponin T ◽  
Pharmacological Study ◽  
Acute Myocardial Ischemia ◽  
Chinese Herbal Compound ◽  
Long Acting ◽  
Traditional Chinese Medicine Preparation ◽  
T Waves

Background: Kuan xiong aerosol (KXA) is a kind of Chinese herbal compound used to regulating qi-flowing for relieving pain and improving angina. However, little pharmacological study of this traditional Chinese medicine preparation has been reported to confirm these activities. Objective: This article aims to observe the effect of resisting acute myocardial ischemia (AMI) in vivo and dilating vessel in vitro of KXA. Materials: The AMI model involves intravenously injecting pituitary (2 U.kg-1) into the ear of rabbits. Electrocardiograph (ECG) T waves were then recorded after administration and the falling range was calculated. Following this, the level of serum Cardiac troponin T (cTn-T) and the histopathology of the cardiac muscle tissue was evaluated. In vitro, the effect of KXA on vasodilation of isolated aortic rings that had been pre-contracted with KCl (30 mM) was observed. Results: It was found KXA reduced ECG ST-T waves and serum cTn-T in the rabbit AMI model, protected myocardial tissue from fracturing and loss of myocardial fibers, and inhibited inflammatory cell infiltration, cavitation degeneration and karyopyknosis of the myocardial matrix. Furthermore, the administration of 0.215, 1.075 and 2.150 mg.mL-1 KXA resulted in significant relaxation of the aortic rings at a rate of 69.63 %, 90.14 % and 118.72 % (p < 0.01) of the untreated ones, and a second shrinkage ratio of 20.17 %, 4.29 %, and 4.54 % (p < 0.01) of the untreated ones, respectively. Conclusions: these results suggest KXA protects against AMI, contributes to dilation of blood vessels and has long-acting effectiveness.

Abstract 423: Proteasome Priming by Protein Kinase G Protects Against Myocardial Ischemia-reperfusion Injury

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Xuejun Wang ◽  
Erin J Terpstra ◽  
Eduardo Callegari ◽  
Chengjun Hu ◽  
Hanming Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
26S Proteasome ◽  
Transgenic Mouse Line ◽  
Pde5 Inhibition ◽  
Myocardial Ischemia Reperfusion

Cardiac proteasome functional insufficiency is implicated in a large subset of heart disease and has been experimentally demonstrated to play an essential role in cardiac proteotoxicity, including desmin-related cardiomyopathy and myocardial ischemia-reperfusion (I-R) injury. Pharmacological inhibition of phosphodiesterase 5 (PDE5) via sildenafil for example, which can stabilize cGMP and thereby increase cGMP-dependent protein kinase (PKG) activity, is consistently reported to protect against I-R injury; however, the underlying mechanism is not fully understood. We have recently discovered that PKG activation enhances proteasomal degradation of misfolded proteins (Ranek, et al. Circulation 2013), prompting us to hypothesize that proteasome-priming may contribute to cardioprotection-induced by PDE5 inhibition. Here we used a cardiomyocyte-restricted proteasome inhibition transgenic mouse line (Tg) and non-Tg (Ntg) littermates to interrogate the action of sildenafil on I-R injury created by left anterior descending artery (LAD) ligation (30 min) and release (24 hr). Sildenafil was administered 30 min before LAD ligation. Results showed that (1) the 26S proteasome activity of the Ntg I-R hearts was significantly elevated by sildenafil but this elevation was blocked in the Tg line; (2) the infarct size reduction by sildenafil treatment in Ntg mice was completely abolished in the Tg mice with the same treatment; and (3) systolic and diastolic function impairment after I/R was markedly attenuated in sildenafil-treated Ntg mice, but not in the sildenafil-treated Tg mice. Additionally, immunoprecipitation assays show that PKG interacted with the proteasome in cultured cardiomyocytes, and this interaction appeared to be augmented by sildenafil treatment. Moreover, in vitro incubation of active PKG with purified human 26S proteasomes increased proteasome peptidase activities and the phosphorylation at specific serine residues of a 19S proteasome subunit as revealed by “gel-free” nano-LC-MS/MS. We conclude that active PKG directly interacts with, phosphorylates, and increases the activities of, the proteasome and that proteasome priming mediates to cardioprotection of PDE5 inhibition against I-R injury.

scholarly journals LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes

2021 ◽  
Vol 8 ◽  
Author(s):  
Cuizhi Li ◽  
Huafeng Song ◽  
Chunlin Chen ◽  
Shaoxian Chen ◽  
Qiyu Zhang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cell Viability ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
H9c2 Cells ◽  
Myocardial Ischemia Reperfusion ◽  
Tissue Specimens ◽  
Masson Staining

Objective: Myocardial ischemia reperfusion (I/R) damage is a life-threatening vascular emergency after myocardial infarction. Here, we observed the cardioprotective effect of long non-coding RNA (lncRNA) PVT1 knockdown against myocardial I/R damage.Methods: This study constructed a myocardial I/R-induced mouse model and a hypoxia/reoxygenation (H/R)-treated H9C2 cells. PVT1 expression was examined via RT-qPCR. After silencing PVT1 via shRNA against PVT1, H&amp;E, and Masson staining was performed to observe myocardial I/R damage. Indicators of myocardial injury including cTnI, LDH, BNP, and CK-MB were examined by ELISA. Inflammatory factors (TNF-α, IL-1β, and IL-6), Gasdermin D (GSDMD), and Caspase1 were detected via RT-qPCR, western blot, immunohistochemistry, or immunofluorescence. Furthermore, CCK-8 and flow cytometry were presented for detecting cell viability and apoptosis.Results: LncRNA PVT1 was markedly up-regulated in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Silencing PVT1 significantly lowered serum levels of cTnI, LDH, BNP, and CK-MB in myocardial I/R mice. H&amp;E and Masson staining showed that silencing PVT1 alleviated myocardial I/R injury. PVT1 knockdown significantly lowered the production and release of inflammatory factors as well as inhibited the expression of GSDMD-N and Caspase1 in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Moreover, silencing PVT1 facilitated cell viability and induced apoptosis of H/R-treated H9C2 cells.Conclusion: Our findings demonstrated that silencing PVT1 could alleviate myocardial I/R damage through suppressing GSDMD-mediated pyroptosis in vivo and in vitro. Thus, PVT1 knockdown may offer an alternative therapeutic strategy against myocardial I/R damage.

Abstract 11710: Poloxamer 188 Protects Coronary Artery Endothelial Cells After Extended Hypoxia and Reoxygenation in an in vitro Model of Simulated Ischemia/Reperfusion Injury

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
zhu li ◽  
Matthew J Hampton ◽  
Matthew B Barajas ◽  
Matthias L Riess
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Calcium Influx ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Membrane Function ◽  
Ldh Release

Reperfusion restores blood flow after myocardial ischemia but can cause additional cellular injury by the sudden reintroduction of oxygen and nutrients. There is still no effective remedy for myocardial ischemia/reperfusion (IR) injury. Our previous study using cardiomyocytes (CMs) found that, after 3 hrs hypoxia followed by 2 hrs reoxygenation, viability decreased, and release of lactate dehydrogenase (LDH), calcium influx, membrane leakage (insertion of fluorescent probe FM1-43) significantly increased, indicating that cell membrane function was negatively affected. This was attenuated by the triblock copolymer Poloxamer (P)188. Here, we first hypothesized that endothelial cells are also susceptible to simulated IR injury, albeit requiring longer hypoxia times. We further hypothesized that P188 can also attenuate simulated IR injury in endothelial cells when given upon reoxygenation. Mouse coronary artery endothelial cells (MCAECs) were exposed to different durations of hypoxia (2, 3, 12 and 24 hrs) in serum- and glucose-free media +/- reoxygenation for 2 hrs in regular media. P188 was administered upon reoxygenation at 0, 100, 300 or 1,000 μM in experiments of 24 hrs hypoxia / 2 hrs reoxygenation. LDH release was measured and compared to appropriately timed normoxic control experiments. Reoxygenation and hypoxia times significantly longer than 3 hrs were required to elicit sufficient injury (panel A). When P188 was given upon reoxygenation after 24 hrs hypoxia, it dose-dependently attenuated LDH release (panel B). These findings contrast to the higher susceptibility of CMs to IR injury that only allowed shorter hypoxia durations. They also confirm a protective effect of P188 on the endothelium, not just on CMs. These findings have important implications for co-culture models with MCAECs and CMs to elucidate the interplay of both cell types on each other when studying mechanisms of cardioprotective strategies and compounds like P188.

An Original Aspirin-Containing Carbonic Anhydrase 9 Inhibitor Overcomes Hypoxia-induced Drug Resistance to Enhance The Efficacy of Myocardial Protection

2021 ◽  
Author(s):  
Wen Zhou ◽  
Bin Zhang ◽  
Keyu Fan ◽  
Xiaojian Yin ◽  
Jinfeng Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Carbonic Anhydrase ◽  
Myocardial Ischemia ◽  
Ph Value ◽  
Acquired Resistance ◽  
Vital Role ◽  
Carbonic Anhydrase 9 ◽  
Myocardial Hypoxia

Abstract Purpose Hypoxic microenvironment plays a vital role in myocardial ischemia injury, generally leading to the resistance of chemotherapeutic drugs. This induces an intriguing study on mechanism exploration and prodrug design to overcome the hypoxia induced drug resistance.Methods In this study, we hypothesized that the overexpression of carbonic anhydrase 9 (CAIX) in myocardial cells is closely related to the drug resistance. Herein, bioinformatics analysis, gene knockdown and overexpression assay certificated the correlation between CAIX overexpression and hypoxia. An original aspirin-containing CAIX inhibitor AcAs has been developed.Results Based on the downregulation of CAIX level, both in vitro and in vivo, AcAs can overcome the acquired resistance, and more effectively attenuate myocardial ischemia and hypoxia injury than that of aspirin. CAIX inhibitor is believed to recover the extracellular pH value so as to ensure the stable effect of aspirin.Conclusion Results indicate great potential of CAIX inhibitor for further application in myocardial hypoxia injury therapy.

NAD glycohydrolase activity in hearts with acute experimental infarction

1976 ◽  
Vol 231 (4) ◽  
pp. 1173-1177 ◽  
Author(s):  
R Nunez ◽  
E Calva ◽  
M Marsch ◽  
E Briones ◽  
F Lopez-Soriano
Keyword(s):  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Normal Tissue ◽  
Equivalent Amount ◽  
Normal Heart ◽  
Nad Glycohydrolase ◽  
Ischemic Tissue ◽  
Hydrolysis Of ◽  
Nad Degradation

Myocardial ischemia was produced in dogs by occluding the descending coronary artery. NAD decreased in the ischemic tissue taken 2 h after the arterial ligature, and an equivalent amount of nicotinamide was detected instead. A further breakdown occurred when fragments of ischemic and nonischemic tissue were incubated at 37 degrees C. In contrast, NAD concentration remained unchanged for as long as 60 min in incubated fragments from normal heart. When normal tissue was homogenized, an immediate hydrolysis of NAD was observed with the formation of stoichiometric amounts of nicotinamide. An excess of nicotinamide completely inhibited the NAD degradation. The NAD glycohydrolase activity assayed in vitro was similar in normal, ischemic, and nonischemic cardiac homogenates. The conclusions are that the NAD loss in the ischemic heart is due to the tissue NAD glycohydrolase activity and that the cell disorganization provoked by the occlusion of the coronary artery seems to facilitate the reaction between the substrate and the enzyme.

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