The role of ERK1/2 signaling pathway in coronary microembolization-induced rat myocardial inflammation and injury

Objectives In this work,we explore the effect of atorvastatin on myocardial apoptosis and caspase-8 acti- vation after coronary microembolization(CME) in rats. Methods Fifty rats were randomly divided into five groups; the coronary microembolization(CME) group,the sham-operated (sham) control group,the gastric lavage control group, the atorvastatin lavage group,and the caspasse-8 inhibitor (N-acetyl-Ile-Glu-Thr-Asp-CHO,abbreviated as CHO) group,with 10 rats for each group.A microembolization ball was injected through the left ventricle for constructing the CME model.Animals in the sham control group were given an injection of physiological saline instead of the microembolization ball.Seven days before the operation,the atorvastatin group underwent gastric lavage with 20 mg/kg of atorvastatin once a day.Gastric lavage control animals underwent gastric lavage with an equivalent dose of physiological saline instead of the atorvastatin.Animals in the CHO group were given an intraperitoneal injection of 10 mg/kg of CHO 30 min before the operation.Six hours after the operation,cardiac ultrasonic detection was conducted on each group to measure the cardiac function indexes.TUNEL(Terminal-deoxynucleoitidyl transferase mediated dUTP nick end labeling) assays were used to measure myocardial apoptosis,and western blots were used to quantify the expression levels of activated caspase-3 and -8.Results(1) The echocardiographic parameters showed that,compared to the sham control animals,the left ventricular ejection fraction(LVEF) of the CME group was significantly decreased(P【0.05).In addition, cardiac sonography revealed a decrease in the left ventricular shortening fraction(FS) and cardiac output(CO), but an increase in the left ventricular end-diastolic dimension (LVEDd).Compared to the CME group,the atorvastatin and CHO groups exhibited significantly improved cardiac function (P【0.05).(2) When compared with the sham control,the myocardical apoptotic rate of the CME group,as well as the levels of activated caspase-3 and-8,increased significantly (P【0.05).The myocardial apoptotic rate,as well as the levels of activated caspase-3 and caspase-8 in the atorvastatin and CHO groups,decreased significandy(P【0.05) in comparison to the CME group.Conclusions The atorvastatin pretreatment clearly suppressed post-CME myocardial apoptosis and improved cardiac function.The most likely mechanism for these effects is the blockade of the myocardial death receptor -mediated apoptosis pathway.

Myosin Specific-T Lymphocytes Mediated Myocardial Inflammation in Adoptive Transferred Rats

Myosin specific-T lymphocytes might mediate myocardial inflammation and remodeling after AMI. Myosin-activated or unactivated T lymphocytes in vitro were transferred into naive syngeneic rats, respectively. T lymphocyte infiltration and myocyte apoptosis were explored by the H＆E and TUNNEL. Proteins and mRNA levels of cytokines （IL-1β, IL-6 and TNF-α） in myocardium were determined by RT-PCR and immunohisto-chemistry. T lymphocyte infiltration was evidently observed after one week of activated T cell transfer. The expressions of cytokines were elevated markedly one week later. The myocyte apoptosis occurred after T lymphocyte infiltration in myocardium. Our findings suggest that cardiac myosin activated-T lymphocytes may mediate myocardial inflammation and remodeling.

The histopathological spectrum of myocardial inflammation in relation to circumstance of death:a retrospective cohort study in clinical and forensic autopsies

Interpreting a myocardial inflammation as causal,contributory or as of no significance at all in the cause of death can be challenging,especially in cases where other pathologic and/or medico-legal findings are also present.To further evaluate the significance of myocardial inflammation as a cause of death we performed a retrospective cohort study of forensic and clinical autopsy cases.We revised the spectrum of histological inflammatory parameters in the myocardium of 79 adult autopsy cases and related these to the reported cause of death.Myocardial slides were reviewed for the distribution and intensity of inflammatory cell infiltrations,the predominant inflammatory cell type,and the presence of inflammation-associated myocyte injury,fibrosis,edema and hemorrhage.Next,the cases were divided over three groups,based on the reported cause of death.Group 1(n=27)consisted of all individuals with an obvious unnatural cause of death.Group 2(n=29)included all individuals in which myocarditis was interpreted to be one out of more possible causes of death.Group 3(n=23)consisted of all individuals in which myocarditis was reported to be the only significant finding at autopsy,and no other cause of death was found.Systematic application of our histological parameters showed that only a diffuse increase of inflammatory cells could discriminate between an incidental presence of inflammation(Group 1)or a potentially significant one(Groups 2 and 3).No other histological parameter showed significant differences between the groups.Our results suggest that generally used histological parameters are often insufficient to differentiate an incidental myocarditis from a(potentially)significant one.

Gualou Xiebai Banxia Decoction(瓜蒌薤白半夏汤) Inhibits NF-kappa B-dependent Inflammation in Myocardial Ischemia-reperfusion Injury in Rats

Objective: To evaluate the myocardial protective effect of Gualou Xiebai Banxia decoction (瓜蒌薤白半夏汤GXBD) and explore the mechanisms of inhibition of NF-kappa B activation and blockade of inflammatory responses induced by ischemia-reperfusion in rats. Methods: Twenty-four Sprague Dawley (SD) rats were randomly divided into three groups. Rats in the treatment group received GXBD (13 g crude drug/kg) for three weeks, while rats in the model control and normal control groups received equal volumes of distilled water. On the 22nd day, rats in the ischemia-reperfusion (I/R) control and GXBD-treated groups underwent 30 min occlusion of the left anterior descending (LAD) coronary artery, followed by 120 min reperfusion. Electrocardiogram was recorded, and the activities of cardiac enzymes, cytokines, and NF-кB were assessed after I/R. Results: Compared with the I/R control group, GXBD treatment restored the activity of the specific myocardial-injury marker creatine kinase (CK) and lactate dehydrogenase (LDH), and inhibited the inflammatory response involving the nuclear factor-кB (NF-кB) pathway, including down-regulation of interleukin (IL)-1β and IL-6, and up-regulation of IL-10 gene expression. Conclusion: GXBD strongly reduced myocardial impairment in our I/R model, including inhibition of NF-кB activation and inflammatory cytokine responses.

Inflammation:an important mechanism for different clinical entities of coronary artery diseases

AIthough atherosclerosis has been considered to be multi-factorial disease in which genetic,environmental, metabolic factors have been implicated, the gaps remain in our knowledge of the etiopathogenesis of atherosclerosis. There is mounting evidence that inflammation plays an important role in the initiation, development as well as evolution of atherosclerosis, suggesting that atherosclerosis is an inflammation disease. Although triggers and pathways of inflammation are probably multiple and different in different clinical settings, the data from animals as well as humans including our groups indicated that an inflammatory process was involved in all stages of atherosclerosis appeared in different clinical entities.