Mouse cardiac surgery: comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies

2004 ◽  
Vol 16 (3) ◽  
pp. 349-360 ◽  
Author(s):  
Oleg Tarnavski ◽  
Julie R. McMullen ◽  
Martina Schinke ◽  
Qing Nie ◽  
Sekwon Kong ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiac Hypertrophy ◽  
Mouse Models ◽  
Surgical Procedures ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Surgical Techniques ◽  
Disease Process ◽  
Human Diseases ◽  
Genomic Studies

Mouse models mimicking human diseases are important tools in trying to understand the underlying mechanisms of many disease states. Several surgical models have been described that mimic human myocardial infarction (MI) and pressure-overload-induced cardiac hypertrophy. However, there are very few detailed descriptions for performing these surgical techniques in mice. Consequently, the number of laboratories that are proficient in performing cardiac surgical procedures in mice has been limited. Microarray technologies measure the expression of thousands of genes simultaneously, allowing for the identification of genes and pathways that may potentially be involved in the disease process. The statistical analysis of microarray experiments is highly influenced by the amount of variability in the experiment. To keep the number of required independent biological replicates and the associated costs of the study to a minimum, it is critical to minimize experimental variability by optimizing the surgical procedures. The aim of this publication was to provide a detailed description of techniques required to perform mouse cardiac surgery, such that these models can be utilized for genomic studies. A description of three major surgical procedures has been provided: 1) aortic constriction, 2) pulmonary artery banding, 3) MI (including ischemia-reperfusion). Emphasis has been placed on technical procedures with the inclusion of thorough descriptions of all equipment and devices employed in surgery, as well as the application of such techniques for expression profiling studies. The cardiac surgical techniques described have been, and will continue to be, important for elucidating the molecular mechanisms of cardiac hypertrophy and failure with high-throughput technology.

Abstract 15863: Macrophage Foxp1 is a Regulator of Pathologic Cardiac Hypertrophy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shuichi Yoneda ◽  
Saptarsi M Haldar ◽  
Jessica Jenkins ◽  
Yunmei Wang ◽  
Teruo Inoue ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Molecular Mechanisms ◽  
Interstitial Fibrosis ◽  
Systolic Dysfunction ◽  
Disease Process ◽  
Left Ventricular ◽  
Negative Regulator ◽  
Control Male ◽  
Pathologic Cardiac Hypertrophy

Introduction: Pathologic cardiac hypertrophy is a maladaptive response to neurohormonal and hemodynamic stress that is a hallmark of human heart failure. While inflammation has been implicated in pathologic hypertrophy, the molecular mechanisms underlying innate immune dysregulation in this disease process are incompletely defined. We have previously demonstrated that the forkhead transcription factor Foxp1 controls monocyte differentiation and suppresses inflammatory activation of macrophages. In this study, we hypothesized that monocyte/macrophage Foxp1 regulates pathologic cardiac hypertrophy. Methods: Macrophage-specific Foxp1 over-expressing (macFoxp1tg=anti-inflammatory) vs. non-tg controls, as well as macrophage-specific Foxp1 knockdown (macFoxp1ko=pro-inflammatory) vs. Cre-control male mice were subject to chronic angiotensin II (AII) infusion (1.8 mcg/kg/min via subcutaneous osmotic mini-pump) for 4 weeks. Results: AII-mediated cardiac hypertrophy (heart mass and cardiomyocyte cross-sectional area), left ventricular (LV) systolic dysfunction, LV dilation, interstitial fibrosis and macrophage (Mac-3+ cells) accumulation were significantly attenuated in macFoxp1tg mice compared to non-tg controls. In contrast, AII-mediated cardiac hypertrophy, LV systolic dysfunction and cavity dilation were significantly exacerbated in macFoxp1ko mice compared to Cre controls. There were no differences in systemic blood pressure between these groups, corroborating a load-independent role for macrophage Foxp1 in cardiac hypertrophy. Conclusion: These studies identify macrophage Foxp1 as a novel negative regulator of pathologic cardiac hypertrophy in vivo. Modulation of Foxp1 signaling may provide a novel strategy for prevention and treatment of heart failure.

scholarly journals Esophageal Cancer: Insights from Mouse Models

2015 ◽  
Vol 8s1 ◽  
pp. CGM.S21218 ◽  
Author(s):  
Marie-Pier Tétreault
Keyword(s):  
Esophageal Cancer ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Human Subjects ◽  
Surgical Techniques ◽  
Therapeutic Strategies ◽  
Human Cancers ◽  
Genetic Modifications ◽  
Wide Range ◽  
Gestation Time

Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Hence, understanding these mechanisms is crucial to improving outcomes for patients with esophageal cancer. Mouse models constitute valuable tools for modeling human cancers and for the preclinical testing of therapeutic strategies in a manner not possible in human subjects. Mice are excellent models for studying human cancers because they are similar to humans at the physiological and molecular levels and because they have a shorter gestation time and life cycle. Moreover, a wide range of well-developed technologies for introducing genetic modifications into mice are currently available. In this review, we describe how different mouse models are used to study esophageal cancer.

Paediatric hydrocephalus

2019 ◽  
pp. 1023-1036
Author(s):  
Matt Bailey ◽  
Chris Parks ◽  
Conor L. Malucci
Keyword(s):  
Cerebrospinal Fluid ◽  
Surgical Procedures ◽  
Surgical Techniques ◽  
Disease Process ◽  
Surgical Care ◽  
Csf Shunts ◽  
Classification Management ◽  
Technological Improvements ◽  
Csf Production

Paediatric hydrocephalus is the commonest disorder to be managed by paediatric neurosurgeons. Rather than representing a single disease process, hydrocephalus can result from a variety of different pathological processes or insults that culminate in an imbalance of cerebrospinal fluid (CSF) production and absorption. If left untreated, the majority of cases are fatal, but with appropriate surgical management most patients survive, with some leading normal lives into adulthood. The mainstay of treatment is with CSF shunts, but with technological improvements in imaging and surgical techniques an increasing number are being successfully treated with neuroendoscopic procedures. The disorder can be complex to manage, with many patients requiring multiple surgical procedures and lifelong follow-up. This chapter gives an overview of paediatric hydrocephalus, its causes and classification, management with shunts and endoscopy, description of surgical techniques, and the outcomes of surgical care.

Aortic Assessment for Cardiac Surgical Procedures

2006 ◽  
Vol 10 (2) ◽  
pp. 158-161 ◽  
Author(s):  
Daniel Bainbridge
Keyword(s):  
Cardiac Surgery ◽  
Transesophageal Echocardiography ◽  
Medical Therapy ◽  
Surgical Procedures ◽  
Heart Surgery ◽  
Surgical Techniques ◽  
Cardiac Surgical Procedures ◽  
Collagen Fibers ◽  
Review Of The Literature ◽  
Perioperative Mortality

Aortic atheromatous disease is associated with stroke in both the ambulatory and perioperative setting. In addition to atheromatous deposits, a reduction in the compliance of the aorta takes place as elastin fibers are replaced by collagen fibers. Both of these distinct processes, termed atherosclerosis, can easily be measured using transesophageal echocardiography during cardiac surgery. A review of the literature demonstrates many studies supporting the benefit of transesophageal echocardiography examination of the aorta for reducing stroke following cardiac surgery, through modification of surgical techniques. There have also been attempts by surgeons to remove atheromatous lesions from the aorta during cardiac surgery. Unfortunately, these procedures currently have a high perioperative mortality. Finally, medical therapy such as warfarin or statins may help reduce the incidence of stroke following heart surgery.

LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

scholarly journals The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

2020 ◽  
Vol 31 (4) ◽  
pp. 716-730 ◽  
Author(s):  
Marc Johnsen ◽  
Torsten Kubacki ◽  
Assa Yeroslaviz ◽  
Martin Richard Späth ◽  
Jannis Mörsdorf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Caloric Restriction ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxic Preconditioning ◽  
Preventive Strategies ◽  
Gene Expression Signatures

BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

scholarly journals microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Li ◽  
Hongbo Zhang ◽  
Zhanhu Li ◽  
Xiaoju Yan ◽  
Yuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

scholarly journals Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

2021 ◽  
Vol 10 (6) ◽  
pp. 1214
Author(s):  
Ji Tu ◽  
Jose Vargas Castillo ◽  
Abhirup Das ◽  
Ashish D. Diwan
Keyword(s):  
Cervical Myelopathy ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Disease Process ◽  
Classification Systems ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Long Term Treatment ◽  
Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

scholarly journals Targeting Ferroptosis Attenuates Interstitial Inflammation and Kidney Fibrosis

2021 ◽  
pp. 1-15
Author(s):  
Lu Zhou ◽  
Xian Xue ◽  
Qing Hou ◽  
Chunsun Dai
Keyword(s):  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Kidney Fibrosis ◽  
Ureter Obstruction ◽  
Regulated Necrosis ◽  
Dependent Form

<b><i>Background:</i></b> Ferroptosis, an iron-dependent form of regulated necrosis mediated by lipid peroxidation, predominantly polyunsaturated fatty acids, is involved in postischemic and toxic kidney injury. However, the role and mechanisms for tubular epithelial cell (TEC) ferroptosis in kidney fibrosis remain largely unknown. <b><i>Objectives:</i></b> The aim of the study was to decipher the role and mechanisms for TEC ferroptosis in kidney fibrosis. <b><i>Methods:</i></b> Mouse models with unilateral ureter obstruction (UUO) or ischemia/reperfusion injury (IRI) were generated. <b><i>Results:</i></b> We found that TEC ferroptosis exhibited as reduced glutathione peroxidase 4 (GPX4) expression and increased 4-hydroxynonenal abundance was appeared in kidneys from chronic kidney disease (CKD) patients and mouse models with UUO or IRI. Inhibition of ferroptosis could largely mitigate kidney injury, interstitial fibrosis, and inflammatory cell accumulation in mice after UUO or IRI. Additionally, treatment of TECs with (1S,3R)-RSL-3, an inhibitor of GPX4, could enhance cell ferroptosis and recruit macrophages. Furthermore, inhibiting TEC ferroptosis reduced monocyte chemotactic protein 1 (MCP-1) secretion and macrophage chemotaxis. <b><i>Conclusions:</i></b> This study uncovers that TEC ferroptosis may promote interstitial fibrosis and inflammation, and targeting ferroptosis may shine a light on protecting against kidney fibrosis in patients with CKDs.

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