Treatment Of Myocardial Injury Research Articles

The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway.

Apoptosis occurs frequently in myocardial infarction, oxidative stress injury, and ischemia/reperfusion injury, and plays a pivotal role in the development of heart diseases. Inhibition of apoptosis alone does not necessarily lead to meaningful rescue in terms of either cardiomyocyte survival or function. Activation of the PI3K/Akt signaling pathway induced by insulin not only inhibits cardiomyocyte apoptosis but also substantially preserves and even improves regional and overall cardiac function. Insulin can protect cardiomyocytes from apoptosis by regulating a number of signaling molecules, such as eNOS, FOXOs, Bad, GSK-3β, mTOR, NDRG2, and Nrf2, through activating PI3K and Akt. This review focuses on the protective mechanisms and targets of insulin identified in the prevention and treatment of myocardial injury.

Screening and identifying the myocardial-injury protective ingredients from Sheng-Mai-San

Context: Sheng-Mai-San (SMS) has been used for the treatment of cardiovascular disease for many years in China.Objectives: This study investigated the protective effects and active ingredients of SMS on myocardial injury (MI) in mice.Materials and methods: SMS and n-butanol extraction of SMS (SMS-Bu) were prepared and administered to ISO-treated mice once a day for 7 consecutive days. The doses were equivalent to the raw medicinal herbs of SMS 5.72, 2.86 and 1.43 g/kg/d, respectively. Propranolol was used as positive control. Serum biomarkers, histopathological and electrocardiographic were evaluated.Results: Serum lactate dehydrogenase, creatine kinase and myeloperoxidase increased to 4473.6 ± 322.5, 950.0 ± 35.0 and 90.4 ± 12.2 U/L in the model group. SMS and SMS-Bu groups showed a decrease from 10 to 29% for lactate dehydrogenase and from 17 to 42% for creatine kinase, respectively. Both SMS and SMS-Bu significantly attenuated the myeloperoxidase activities (from 42 to 56%) and malondialdehyde levels (from 25 to 45%) compared with the model group. Decreased superoxide dismutase activities in ISO-treated mice were elevated from 19 to 59% when treated with SMS and SMS-Bu. These biochemical results were supported by electrocardiogram (ECG) and histopathological observations. Furthermore, 8 ginsenosides and 16 lignans were identified in SMS-Bu.Conclusion: These findings suggested that SMS-Bu was the mainly active fraction of SMS which exerted its beneficial effects on MI mainly through protecting myocardial tissue and reducing oxidative damage, and the ginsenosides and lignans may serve as active ingredients of SMS for the treatment of MI.

Inhibition of N -Ethylmaleimide–Sensitive Factor Protects Against Myocardial Ischemia/Reperfusion Injury

Exocytosis of endothelial granules promotes thrombosis and inflammation and may contribute to the pathophysiology of early reperfusion injury following myocardial ischemia. TAT-NSF700 is a novel peptide that reduces endothelial exocytosis by inhibiting the ATPase activity and disassembly activity of N-ethylmaleimide-sensitive factor (NSF), a critical component of the exocytic machinery. We hypothesized that TAT-NSF700 would limit myocardial injury in an in vivo murine model of myocardial ischemia/reperfusion injury. Mice were subjected to 30 minutes of ischemia followed by 24 hours of reperfusion. TAT-NSF700 or the scrambled control peptide TAT-NSF700scr was administered intravenously 20 minutes before the onset of ischemia. Myocardial ischemia/reperfusion caused endothelial exocytosis, myocardial infarction, and left ventricular dysfunction. However, TAT-NSF700 decreased von Willebrand factor levels after myocardial ischemia/reperfusion, attenuated myocardial infarct size by 47%, and preserved left ventricular structure and function. These data suggest that drugs targeting endothelial exocytosis may be useful in the treatment of myocardial injury following ischemia/reperfusion.

GCSF Treatment for Non-Ischemic Dilated Cardiomyopathy

In 2001 research of endogenous cell therapy started. Orlic et al. reported that granulocyte colony-stimulating factor (GCSF) and stem-cell-factor (SCF) improved heart function and the survival rate after myocardial infarction [1]. They showed that the infarcted scar got smaller with newly-formed myocardium dramatically. Because they did not label bone marrow cells, it was not sure where the majority was originated from. To clarify this issue we tagged bone marrow cells with GFP for tracking [2]. Survival rate was improved with GCSF. However, Bone marrow-derived myogenic cells were too small number to contribute to pump function directly [3]. This observation made researchers to go to other directions. Wei et al. clearly showed that in doxorubicininduced cardiomyopathy the protein expression of Fas was attenuated by GCSF and apoptosis of cardiomyocytes was inhibited and ultrastructure of myocardium was well preserved. Finally GCSF improved heart function, which was confirmed by pressure study and echocardiography. This mechanism of GCSF treatment was consistent with infarction model [4]. GCSF receptors are expressed on cardiomyocytes in idiopathic dilated cardiomyopathy in human, too [5]. GCSF affected not only bone marrow to mobilize cells to migrate into diseased heart but also cardiomyocytes directly through GCSF receptors. In the time course rats received GCSF from 2 weeks after doxorubicin induction. At the period of GCSF treatment myocardium is still in the subacute phase after doxorubicin. We observed that GCSF effectiveness was vague 3 weeks after doxorubicin induction [6]. It is likely to have much more effectiveness just after insult such as infarction [4], cardiotoxic drug, and so on. However, in the clinical setting, end-staged dilated cardiomyopathy is the reality. GCSF strategy should be investigated in the chronic phase in the further study. GCSF regimen such as dose, frequency, and duration should be optimized, too. As a preclinical study nonischemic cardiomyopathy in large animal models should be investigated. There are other possible mechanisms of GCSF. First, the healing process. Minatoguchi et al. reported that GCSF accelerates absorption of necrotic tissues via increase of macrophages and reduces granulation and scar tissues via expression of MMPs [7]. Second, cardiac resident stem cells. Oh et al. reported that Sca 1(+ ) cells reside at the central fibrous body and atrium and they can be expanded in vitro and differentiate into cardiomyocytes, endothelial cells, and smooth muscle cells [8]. Cardiac resident stem cells may play an important role in the GCSF treatment. Third, other roles of bone marrowderived cells. Interpretations of mobilized bone marrow cells by Skalak’s lab is interesting [9]. They reported that mobilization of bone marrow-derived cells enhanced the angiogenic response to hypoxia without transdifferentiation into endothelial cells. Adult stem cells may work as supervisors, not doing the heavy lifting themselves. It will take some time to clarify what is the major mechanism to improve damaged heart function with GCSF treatment. Sata et al. reported that hematopoietic stem cells may contribute to atherosclerosis [10]. It raised the important point that endogenous-stem cells could migrate into both injured myocardium and atherosclerotic lesions. If we can elucidate the physiological mechanism of endogenous-stem cell migration, we may be better able to control this process in the future treatment of myocardial injury. Everybody is seeking a chunk of neo-muscle to rebuild diseased heart by cell-based therapy for years. However, no report has shown such a dramatic picture, yet. Further investigation should be focused on not only stem cells but other cells and surrounding components to establish new strategy for endstaged heart failure.

Protective effects of melatonin against myocardial injury induced by isoproterenol in rats.

This study was performed to determine whether melatonin could have a protective effect against myocardial injury (MI) induced by isoproterenol (ISO) in rats. Twenty-four rats were divided into three treatment groups: (1) control (n = 8): saline solution. (2) ISO (n = 8): ISO only. (3) melatonin + ISO (n = 8). Melatonin (10 mg/kg/day, i.p.) was administered 30 min before the initiation of ISO (150 mg/kg/day, s.c.). Drugs and saline were given at 14:00 hr for two consecutive days. At the end of the second day, blood samples were taken from the abdominal aorta shortly after the rats were anesthetized for the purpose of measuring cardiac troponins T (cTnT) and I (cTnI); hearts were removed, preserved and examined microscopically. Additionally, based on the histological changes in myocardial tissue, the rats were divided into three groups: no change, mild changes and moderate and/or marked changes. The mean cTnT and cTnI values were significantly increased in ISO group compared with control group [(1.29 +/- 0.22 ng/mL versus 0.46 +/- 0.07 ng/mL, P < 0.0001) and (0.56 +/- 0.11 ng/mL versus 0.21 +/- 0.01 ng/mL, P < 0.001)], respectively, and were significantly reduced in the ISO + melatonin group (0.65 +/- 0.06 ng/mL for cTnT and 0.25 +/- 0.01 ng/mL for cTnI) compared with the ISO only group (P < 0.01), respectively. cTnT and cTnI values were significantly increased in rats with moderate and/or marked cardiac changes compared with hearts where there were mild changes and no change (P < 0.05). ISO + melatonin group showed less histological changes than the ISO group (P < 0.01). In conclusion, this study revealed a protective effect of melatonin against ISO-induced MI in rats, and its potential clinical application in the treatment of MI.