Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

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Faculty Opinions recommendation of Absence of type VI collagen paradoxically improves cardiac function, structure, and remodeling after myocardial infarction.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13945983.15401088 ◽

2012 ◽

Author(s):

Anthony Dart

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Function Structure ◽

Type Vi Collagen

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Author Correction: In vivo transduction of ETV2 improves cardiac function and induces vascular regeneration following myocardial infarction

Experimental & Molecular Medicine ◽

10.1038/s12276-019-0271-x ◽

2019 ◽

Vol 51 (9) ◽

pp. 1-1 ◽

Cited By ~ 1

Author(s):

Sunghun Lee ◽

Dong Hun Lee ◽

Bong-Woo Park ◽

Ri Youn Kim ◽

Anh Duc Hoang ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Vascular Regeneration

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Voluntary exercise and cardiac remodeling in a myocardial infarction model

Open Medicine ◽

10.1515/med-2020-0109 ◽

2020 ◽

Vol 15 (1) ◽

pp. 545-555

Author(s):

Hamad Al Shahi ◽

Tomoyasu Kadoguchi ◽

Kazunori Shimada ◽

Kosuke Fukao ◽

Satoshi Matsushita ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Cardiac Remodeling ◽

Skeletal Muscles ◽

Wheel Running ◽

Voluntary Exercise ◽

Fibroblast Growth Factor 21 ◽

Expression Levels ◽

Factor Α ◽

Necrosis Factor

AbstractWe investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1β, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles.

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Neutrophil Elastase Deficiency Ameliorates Myocardial Injury Post Myocardial Infarction in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22020722 ◽

2021 ◽

Vol 22 (2) ◽

pp. 722

Author(s):

Yukino Ogura ◽

Kazuko Tajiri ◽

Nobuyuki Murakoshi ◽

DongZhu Xu ◽

Saori Yonebayashi ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Neutrophil Elastase ◽

Myocardial Injury ◽

Flow Cytometric Analysis ◽

Akt Signaling ◽

Border Zone ◽

Terminal Deoxynucleotidyl Transferase ◽

Deficient Mice

Neutrophils are recruited into the heart at an early stage following a myocardial infarction (MI). These secrete several proteases, one of them being neutrophil elastase (NE), which promotes inflammatory responses in several disease models. It has been shown that there is an increase in NE activity in patients with MI; however, the role of NE in MI remains unclear. Therefore, the present study aimed to investigate the role of NE in the pathogenesis of MI in mice. NE expression peaked on day 1 in the infarcted hearts. In addition, NE deficiency improved survival and cardiac function post-MI, limiting fibrosis in the noninfarcted myocardium. Sivelestat, an NE inhibitor, also improved survival and cardiac function post-MI. Flow cytometric analysis showed that the numbers of heart-infiltrating neutrophils and inflammatory macrophages (CD11b+F4/80+CD206low cells) were significantly lower in NE-deficient mice than in wild-type (WT) mice. At the border zone between intact and necrotic areas, the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells was lower in NE-deficient mice than in WT mice. Western blot analyses revealed that the expression levels of insulin receptor substrate 1 and phosphorylation of Akt were significantly upregulated in NE-knockout mouse hearts, indicating that NE deficiency might improve cardiac survival by upregulating insulin/Akt signaling post-MI. Thus, NE may enhance myocardial injury by inducing an excessive inflammatory response and suppressing Akt signaling in cardiomyocytes. Inhibition of NE might serve as a novel therapeutic target in the treatment of MI.

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Endothelial β1 Integrin-Mediated Adaptation to Myocardial Ischemia

Thrombosis and Haemostasis ◽

10.1055/s-0040-1721505 ◽

2021 ◽

Author(s):

Carina Henning ◽

Anna Branopolski ◽

Paula Follert ◽

Oksana Lewandowska ◽

Aysel Ayhan ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Myocardial Ischemia ◽

Cardiac Function ◽

Integrin Subunit ◽

Β1 Integrin ◽

Human Coronary Artery ◽

Tetrazolium Chloride ◽

Magnetic Resonance Imaging Mri ◽

Interfering Rna

Abstract Background Short episodes of myocardial ischemia can protect from myocardial infarction. However, the role of endothelial β1 integrin in these cardioprotective ischemic events is largely unknown. Objective In this study we investigated whether endothelial β1 integrin is required for cardiac adaptation to ischemia and protection from myocardial infarction. Methods Here we introduced transient and permanent left anterior descending artery (LAD) occlusions in mice. We inhibited β1 integrin by intravenous injection of function-blocking antibodies and tamoxifen-induced endothelial cell (EC)-specific deletion of Itgb1. Furthermore, human ITGB1 was silenced in primary human coronary artery ECs using small interfering RNA. We analyzed the numbers of proliferating ECs and arterioles by immunohistochemistry, determined infarct size by magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride staining, and analyzed cardiac function by MRI and echocardiography. Results Transient LAD occlusions were found to increase EC proliferation and arteriole formation in the entire myocardium. These effects required β1 integrin on ECs, except for arteriole formation in the ischemic part of the myocardium. Furthermore, this integrin subunit was also relevant for basal and mechanically induced proliferation of human coronary artery ECs. Notably, β1 integrin was needed for cardioprotection induced by transient LAD occlusions, and the absence of endothelial β1 integrin resulted in impaired growth of blood vessels into the infarcted myocardium and reduced cardiac function after permanent LAD occlusion. Conclusion We showed that endothelial β1 integrin is required for adaptation of the heart to cardiac ischemia and protection from myocardial infarction.

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