It has been shown that a lot of diseases were related with the change or loss of Cl- channel functions. Among the Cl- channels, volume-regulated anion channel (VRAC) plays important roles in myocardial ischemia/reperfusion injury, cardiac arrhythmia and apoptosis; it may become a new target in the clinical treatment of heart diseases. This paper presents an overview of the physiological characteristics of VRAC and its relations with myocardial ischemia/reperfusion injury.
Chloride Channels ; classification ; metabolism ; physiology ; Humans ; Myocardial Reperfusion Injury ; metabolism

Rats ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Luteolin/metabolism* ; Down-Regulation ; Rats, Sprague-Dawley ; MicroRNAs/metabolism* ; Reperfusion Injury ; Apoptosis

OBJECTIVE: To test cathepsin L as a biomarker of myocardial ischemia by examination of cathepsin L expression in plasma after myocardial ischemia and ischemia-reperfusion in rats. METHODS: The rat models were established and divided in acute myocardial ischemia model (myocardial ischemia 30 min, 1 h, 2 h groups), ischemia-reperfusion model (ischemia-reperfusion group), and isoflurane-pretreated ischemia-reperfusion model (isoflurane-pretreated group), respectively. Normal control group and sham-operated group were established as contrast. The contents of cathepsin L in plasma were examined by ELISA and myocardial infarction areas were measured after TTC staining. RESULTS: No statistical significant changes were found among the experimental groups compared with the normal control group and sham-operated group (P>0.05). The cathepsin L from the ischemia-reperfusion group increased to 2.37 times compared with the normal control group (P<0.05). The cathepsin L and myocardium infarction size of isoflurane-pretreated group decreased compared with the ischemia-reperfusion group (P<0.05). CONCLUSION The cathepsin L in plasma is not a promising biomarker of acute myocardial ischemia. Isoflurane preconditioning can reduce the cathepsin L in plasma caused by ischemia-reperfusion injury.
Animals ; Biomarkers/blood* ; Cathepsin L/analysis* ; Isoflurane ; Myocardial Infarction/metabolism* ; Myocardial Ischemia ; Myocardial Reperfusion Injury/metabolism* ; Myocardium ; Rats

Fibroblast growth factor 21 (FGF21) is a growth factor with endocrine function in the fibroblast growth factor family. Previous reports have shown that FGF21 is involved in the regulation of energy metabolism and plays a protective role in cardiovascular diseases such as coronary heart disease, diabetes, non-alcoholic fatty liver disease and so on. Recent studies have found that FGF21 can induce autophagy in a variety of tissues and organs, and autophagy is involved in many pathological processes of cardiovascular diseases, including vascular calcification, atherosclerosis, and myocardial ischemia-reperfusion injury. Therefore, FGF21 may play a protective role in a variety of cardiovascular diseases by regulating autophagy. This article reviews the research progress on the protective role of FGF21 in cardiovascular diseases by inducing autophagy.
Autophagy/physiology* ; Cardiovascular Diseases/metabolism* ; Fibroblast Growth Factors/metabolism* ; Humans ; Myocardial Reperfusion Injury/metabolism*

Humans ; Ischemia ; metabolism ; pathology ; therapy ; Ischemic Postconditioning ; methods ; Myocardial Reperfusion Injury ; metabolism ; pathology ; therapy

Ischemia/hypoxia is one of the key clinical issues following severe burns, and ischemic/hypoxic damage of tissues and organs is still hard to be prevented or minimized by various fluid resuscitation regimens. To those who suffered severe burns, even though fluid replacement therapy is delivered promptly, ischemic/hypoxic damage of organs is still inevitable. Previously, blood flow in vital organs such as heart was considered not to be reduced because of blood redistribution under the circumstance of stress. The postburn cardiac dysfunction has been mainly attributed to the reduced blood flow returned to the heart due to decreased blood volume caused by increased capillary permeability. Therefore, postburn cardiac dysfunction has been considered to be the result of burn shock. During the past two decades, we have performed serial studies on severe burns, and found that ischemic/hypoxic myocardial damage and functional impairment of myocardium due to activation of renin angiotensin system existing in the heart itself occur immediately after severe burns even before significant reduction in blood volume secondary to an increase of capillary permeability. Such prompt myocardial damage leads to cardiac deficiency, and it is also a precipitating factor for burn shock and ischemic/hypoxic injury of systemic tissues and organs. Therefore, we called it "shock heart" in our reports. The cellular and molecular mechanisms leading to myocardial damage were systematically investigated. Strategies for prevention of early postburn myocardial damage and dysfunction, and a new effective burn shock resuscitation regimen "volume replacement" plus "dynamic support" (cardiac support and myocardial protection) have been proposed based on our previous studies.
Burns ; complications ; metabolism ; Humans ; Hypoxia ; etiology ; prevention & control ; Myocardial Reperfusion Injury ; etiology ; prevention & control ; Myocardium ; metabolism

BackgroundOxygen-glucose deprivation-nutrition resumption (OGD-NR) models on H9c2 cells are commonly used in vitro models of simulated myocardial ischemia-reperfusion injury (MIRI), but no study has assessed whether these methods for establishing in vitro models can effectively imitate the characteristics of MIRI in vivo. This experiment was designed to analyze the feasibility of six OGD-NR models of MIRI.

MethodsBy searching the PubMed database using the keywords "myocardial reperfusion injury H9c2 cells," we obtained six commonly used OGD-NR in vitro models of MIRI performed on H9c2 cells from more than 400 published papers before January 30, 2017. For each model, control (C), simulated ischemia (SI), and simulated ischemia-reperfusion (SIR) groups were assigned, and cell morphology, lactate dehydrogenase (LDH) release, adenosine triphosphate (ATP) levels, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and inflammatory cytokines were examined to evaluate the characteristics of cell injury. Subsequently, a coculture system of cardiomyocyte-endothelial-macrophage was constructed. The coculture system was dealt with SI and SIR treatments to test the effect on cardiomyocytes survival.

ResultsFor models 1, 2, 3, 4, 5, and 6, SI treatment caused morphological damage to cells, and subsequent SIR treatment did not cause further morphological damage. In the models 1, 2, 3, 4, 5 and 6, LDH release was significantly higher in the SI groups than that in the C group (P < 0.05), and was significantly lower in the SIR groups than that in the SI groups (P < 0.05), except for no significant differences in the LDH release between C, SI and SIR groups in model 6 receiving a 3-h SI treatment. In models 1, 2, 3, 4, 5, and 6, compared with the C group, ATP levels of the SI groups significantly decreased (P < 0.05), ROS levels increased (P < 0.05), and MMP levels decreased (P < 0.05). Compared with the SI group, ATP level of the SIR groups was significantly increased (P < 0.05), and there was no significant ROS production, MMP collapse, and over inflammatory response in the SIR groups. In a coculture system of H9c2 cells-endothelial cells-macrophages, the proportion of viable H9c2 cells in the SIR groups was not reduced compared with the SI groups.

ConclusionAll the six OGD-NR models on H9c2 cells in this experiment can not imitate the characteristics of MIRI in vivo and are not suitable for MIRI-related study.

Apoptosis ; Glucose ; metabolism ; Humans ; Myocardial Reperfusion Injury ; physiopathology ; Myocytes, Cardiac ; physiology ; Oxygen ; metabolism

Cardiomyocytes injury model has been widely used in the study for the molecular mechanism of cardiovascular diseases and drug action. It is very important to select the appropriate model due to the different formation mechanisms for various models. Clinical cardiovascular pathological change is relatively complex. Currently used models according to the characteristics of clinical cardiovascular diseases mainly include hydrogen peroxide-induced myocardial cell damage model, hypoxia reoxygenation injury model, adriamycin-induced myocardial cell damage model, high sugar high fat-induced myocardial cell damage model, and isoprenaline-induced myocardial cell damage model. Every model has its advantages as well as its disadvantages. The suitable model of myocardial cell injury can be selected according to the research purpose.
Animals ; Cell Hypoxia ; Myocardial Reperfusion Injury/metabolism* ; Myocardium ; Myocytes, Cardiac/metabolism* ; Rats ; Rats, Sprague-Dawley ; Research

Mitophagy is one of the important targets for the prevention and treatment of myocardial ischemia/reperfusion injury (MIRI). Moderate mitophagy can remove damaged mitochondria, inhibit excessive reactive oxygen species accumulation, and protect mitochondria from damage. However, excessive enhancement of mitophagy greatly reduces adenosine triphosphate production and energy supply for cell survival, and aggravates cell death. How dysfunctional mitochondria are selectively recognized and engulfed is related to the interaction of adaptors on the mitochondrial membrane, which mainly include phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced kinase 1/Parkin, hypoxia-inducible factor-1 α/Bcl-2 and adenovirus e1b19k Da interacting protein 3, FUN-14 domain containing protein 1 receptor-mediated mitophagy pathway and so on. In this review, the authors briefly summarize the main pathways currently studied on mitophagy and the relationship between mitophagy and MIRI, and incorporate and analyze research data on prevention and treatment of MIRI with Chinese medicine, thereby provide relevant theoretical basis and treatment ideas for clinical prevention of MIRI.
Humans ; Mitochondria/metabolism* ; Mitophagy/genetics* ; Myocardial Reperfusion Injury ; Protein Kinases/metabolism*

OBJECTIVETo observe the alteration of cardiac myocyte nuclear inositol 1,3,4,5-tetrakisphosphate receptor (IP(4)R) binding properties in rat subjected to myocardial ischemic reperfusion in order to further make it clear whether this change is involved in the molecule mechanism of cell apoptosis of rat with myocardial ischemic reperfusion.

METHODSExtracting of cardiac myocyte nucleus was accomplished by saccharose density gradient centrifugation method, the binding properties of nuclear IP(4)R in different conditions were detected by radioligand binding assay. Apoptosis index of myocardial cell was determined by using TUNEL assay.

RESULTS(1) Myocardial cell apoptosis index in rat heart underwent 30 min regional ischemia and 3 h reperfusion increased distinctly compared with that in control group (P < 0.01). (2) There were two IP(4) binding sites located to the nuclear envelope. (3) In ischemic reperfusion injury (IRI) group, Bmax from high affinity binding site of nuclear IP(4)R significantly increased compared with that in sham-operated group, whereas Bmax from low affinity binding site didn't change. Kd values of both sites were all significantly decreased by 63% and 55%, respectively. (4) Phosphorylation of nuclear IP(4)R by PKC increased markedly its binding ability both in IRI and control group (P < 0.05), which was more apparent in IRI group. (5) In sham-operated group, the binding ability of nuclear IP(4)R increased with increasing free calcium concentrations in cytoplasm, and the binding properties of IP(4)R in IRI group were also increased in the condition of calcium overloading.

CONCLUSIONThe increasing of binding properties of nuclear IP(4)R from ischemic reperfusion heart may be one of important mechanism involved in myocardial cell apoptosis, furthermore resulting in myocardial IRI.

Animals ; Apoptosis ; Cell Nucleus ; metabolism ; Male ; Myocardial Reperfusion ; Myocardial Reperfusion Injury ; metabolism ; pathology ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Wistar ; Receptors, Cytoplasmic and Nuclear ; metabolism