ABSTRACT
PURPOSE OF REVIEW: The advent of induced pluripotent stem cells (iPSC) has paved the way for new in vitro models of human cardiomyopathy. Herein, we will review existing models of disease as well as strengths and limitations of the system. RECENT FINDINGS: Preclinical studies have now demonstrated that iPSCs generated from patients with both acquired or heritable genetic diseases retain properties of the disease in vitro and can be used as a model to study novel therapeutics. iPSCs can be differentiated in vitro into the cardiomyocyte lineage into cells resembling adult ventricular myocytes that retain properties of cardiovascular disease from their respective donor. iPSC pluripotency allows for them to be frozen, stored, and continually used to generate iPSC-derived myocytes for future experiments without need for invasive procedures or repeat myocyte isolations to obtain animal or human cardiac tissues. While not without their limitations, iPSC models offer new ways for studying patient-specific cardiomyopathies. iPSCs offer a high-throughput avenue for drug development, modeling of disease pathophysiology in vitro, and enabling experimental repair strategies without need for invasive procedures to obtain cardiac tissues.
Subject(s)
Cardiomyopathies , Cardiovascular Diseases , Induced Pluripotent Stem Cells , Animals , Cardiomyopathies/genetics , Cardiovascular Diseases/therapy , Cell Differentiation , Humans , Myocytes, CardiacABSTRACT
Left ventricular noncompaction (LVNC) is a highly heterogeneous primary disorder of the myocardium. Its clinical features and genetic spectrum strongly overlap with other types of primary cardiomyopathies, in particular, hypertrophic cardiomyopathy. Study and the accumulation of genotype-phenotype correlations are the way to improve the precision of our diagnostics. We present a familial case of LVNC with arrhythmic and thrombotic complications, myocardial fibrosis and heart failure, cosegregating with the splicing variant in the FHOD3 gene. This is the first description of FHOD3-dependent LVNC to our knowledge. We also revise the assumed mechanism of pathogenesis in the case of FHOD3 splicing alterations.
Subject(s)
Cardiomyopathies , Cardiomyopathy, Hypertrophic , Heart Defects, Congenital , Isolated Noncompaction of the Ventricular Myocardium , Cardiomyopathies/genetics , Cardiomyopathy, Hypertrophic/complications , Formins , Heart Defects, Congenital/pathology , Humans , Isolated Noncompaction of the Ventricular Myocardium/diagnostic imaging , Isolated Noncompaction of the Ventricular Myocardium/genetics , MyocardiumABSTRACT
Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.
Subject(s)
COVID-19/immunology , COVID-19/physiopathology , Cardiomyopathies/immunology , Coronary Artery Disease/immunology , Venous Thromboembolism/immunology , COVID-19/complications , COVID-19/genetics , Cardiomyopathies/complications , Cardiomyopathies/genetics , Coronary Artery Disease/complications , Coronary Artery Disease/genetics , Cytokines/genetics , Datasets as Topic , Humans , Immunocompromised Host/genetics , Inflammasomes/genetics , Lymphocyte Count , Patient Acuity , RNA-Seq , Venous Thromboembolism/complicationsABSTRACT
Inherited heart disease represent a very heterogenous group of cardiac disorders, characterized by inherited, acquired, and often rare disorders affecting the heart muscle (cardiomyopathies) or the cardiac electrical system (ion channel disease). They are often familial diseases, and are among the leading cause of juvenile sudden death and heart failure. The aim of this paper is to give a perspective on how to run a clinical service during an epidemic or pandemic emergency and to describe the potential COVID-19 associated risks for patients affected by inherited heart diseases.