Correction to: Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

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.

Download Full-text

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.

Download Full-text

Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes

Scientific Reports ◽

10.1038/s41598-021-91900-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jonathan A. Shulgach ◽

Dylan W. Beam ◽

Ameya C. Nanivadekar ◽

Derek M. Miller ◽

Stephanie Fulton ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Fibers ◽

The Body ◽

Evoked Responses ◽

Gi Tract ◽

Selective Stimulation ◽

Nerve Cuff ◽

Cuff Electrodes ◽

Nerve Cuff Electrodes ◽

Stimulation Of

AbstractDysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the left or right nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that it was possible to selectively activate subpopulations of vagal neurons using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e., Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.

Download Full-text

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.

Download Full-text