Myocardial Death Research Articles

Group 2 innate lymphoid cells contribute to IL-33-mediated alleviation of cardiac fibrosis.

Rationale: The major cause of heart failure is myocardium death consequent to detrimental cardiac remodeling and fibrosis following myocardial infarction. The cardiac protective cytokine interleukin (IL)-33, which signals by ST2 receptor binding, is associated with group 2 innate lymphoid cell (ILC2) activation and regulates tissue homeostasis and repair following tissue injury in various tissues. However, the distribution and role of IL-33-responsive ILC2s in cardiac fibrosis remain unclear. In this study, we elucidated the roles of IL-33-responsive cardiac-resident ILC2s and IL-33-mediated immunomodulatory functions in cardiac fibrosis.Methods: We examined the distribution of cardiac ILC2s by using flow cytometry. The roles of IL-33-mediated ILC2 expansion in cardiac fibrosis was evaluated in the mouse model of catecholamine-induced cardiac fibrosis. ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice were implemented to determine the contribution of endogenous ILC in the progression of cardiac fibrosis. Histopathological assessments, speckle tracking echocardiography, and transcriptome profile analysis were performed to determine the effects of IL-33-mediated cardiac protective functions.Results: We identified the resident cardiac ILC2s, which share similar cell surface marker and transcriptional factor expression characteristics as peripheral blood and lung tissue ILC2s. IL-33 treatment induced ILC2 expansion via ST2. In vivo, ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice developed exacerbated cardiac fibrosis following catecholamine-induced stress cardiac injury. IL-33 treatment expanded cardiac ILC2s and revealed protective effects against cardiac tissue damage with reduced cardiomyocyte death, immune cell infiltration, tissue fibrosis, and improved myocardial function. Transcriptome analysis revealed that IL-33 attenuated extracellular matrix synthesis- and fibroblast activation-associated gene expressions. IL13-knockout or epidermal growth factor receptor (EGFR) inhibition abolished IL-33-mediated cardiac protective function, confirming IL-13 and EGFR signaling as crucial for IL-33-mediated cardioprotective responses. Moreover, ILC2-produced BMP-7 served as a novel anti-fibrotic factor to inhibit TGF-β1-induced cardiac fibroblast activation.Conclusion: Our findings indicate the presence of IL-33-responsive ILC2s in cardiac tissue and that IL-33-mediated ILC2 expansion affords optimal cardioprotective function via ILC2-derived factors. IL-33-mediated immunomodulation is thus a promising strategy to promote tissue repair and alleviate cardiac fibrosis following acute cardiac injury.

Cardiomyocyte Induction and Regeneration for Myocardial Infarction Treatment: Cell Sources and Administration Strategies.

Occlusion of coronary artery and subsequent damage or death of myocardium can lead to myocardial infarction (MI) and even heart failure-one of the leading causes of deaths world wide. Notably, myocardium has extremely limited regeneration potential due to the loss or death of cardiomyocytes (i.e., the cells of which the myocardium is comprised) upon MI. A variety of stem cells and stem cell-derived cardiovascular cells, in situ cardiac fibroblasts and endogenous proliferative epicardium, have been exploited to provide renewable cellular sources to treat injured myocardium. Also, different strategies, including direct injection of cell suspensions, bioactive molecules, or cell-incorporated biomaterials, and implantation of artificial cardiac scaffolds (e.g., cell sheets and cardiac patches), have been developed to deliver renewable cells and/or bioactive molecules to the MI site for the myocardium regeneration. This article briefly surveys cell sources and delivery strategies, along with biomaterials and their processing techniques, developed for MI treatment. Key issues and challenges, as well as recommendations for future research, are also discussed.

Mouse model for myocardial injury caused by ischemia

In the current, cardiovascular disease is one of the leading causes of death in the World. Coronary artery blockage causes acute myocardial infarction that makes myocardial tissue is damaged and can be fatal in some cases. If patients overcome the acute infarctions, the obstruction in the long run will lead to myocardial ischemia and then cell death in the ischemic myocardium area. So far there is no method to prevent effectively myocardial lesions, the development of an animal model of myocardial injury is necessary for studying new therapies for the treatment. This study aimed to create a mouse model of myocardial injury. An occluding suture of the left coronary artery in mice was made with sewing thread Prolene 7-0. That left anterior descending artery (LAD) closing caused the infarction leading to ischemia and death of cells after that. The animals were then monitored survival ratio, body weight, blood pressure and analyzed Histopathology using Hematoxylin and Eosin (H&E) stain, Trichrome stain, and Immunohistochemistry (IHC) stain to evaluate the injuries of myocardium. The results showed that six weeks after narrowing the left coronary artery, the survival percentage of the experimental group was 77% (survival 17/22), body weight and blood pressure of the experimental group (n=17) tended to decrease comparing to the control group (n=10) or heart function of the experimental group was weakening. Supporting for that result, Histopathology assessments were also showed that the damages and the death of myocardium in the experiment group. H&E stain gave the presentation that heart septum of the experimental group was thinner than the control group. Collagen formation was also observed in the experimental group by Trichrome stain results. In addition, IHC stain also indicated that the Annex-in- V (death cell marker) was expressed much stronger than those of the control group. In conclusion, the mouse model for myocardial injury caused by ischemia has been created successfully by LAD ligation.