elastin and Endocardial-Fibroelastosis

Topics: Aging; Amino Acids; Aneurysm; Animals; Arteriosclerosis; Brain Diseases; Copper; Deficiency Diseases; Elastic Tissue; Elastin; Endocardial Fibroelastosis; Growth Disorders; Hair; Humans; Inflammation; Lathyrism; Marfan Syndrome; Metabolic Diseases; Respiratory Tract Diseases; Skin Diseases

Endothelial-to-mesenchymal transition (EndMT) has been identified as the underlying mechanism of endocardial fibroelastosis (EFE) formation. The purpose of this study was to determine whether hemodynamic alterations due to valvar defects promote EndMT and whether age-specific structural changes affect ventricular diastolic compliance despite extensive surgical resection of EFE tissue.. We analyzed EFE tissue from 24 patients with hypoplastic left heart syndrome (HLHS) who underwent left ventricular (LV) rehabilitation surgery at Boston Children's Hospital between December 2011 and March 2018. Six patients with flow disturbances across the aortic valve and/or mitral valve but no HLHS diagnosis and macroscopic appearance of "EFE-like tissue" in the LV were included for comparison. All samples were examined for amount of collagen/elastin production and degradation, and presence of active EndMT by histologic analysis.. EFE tissue from patients with and without HLHS consisted predominantly of elastin and collagen fibers. There was no alteration in degradation activity for collagen or elastin as shown by in situ zymography. Active EndMT was found in all patients with and without HLHS with flow disturbances ("EFE-like"). In patients with HLHS, EFE infiltrated into the underlying myocardium with increasing age.. Patients with and without HLHS with flow disturbances due to stenotic or incompetent valves develop EndMT-derived fibrotic tissue covering the LV. When EFE recurs, it is directly associated with flow disturbances and switches to an infiltrative growth pattern with increasing age, leading to increased diastolic stiffness of the LV.

Topics: Cardiac Surgical Procedures; Child; Child, Preschool; Cohort Studies; Collagen; Elastin; Endocardial Fibroelastosis; Heart Ventricles; Hemodynamics; Humans; Hypoplastic Left Heart Syndrome; Infant

Hypoplastic left heart syndrome (HLHS) is one of the most common severe congenital cardiac anomalies, characterized by a marked hypoplasia of left-sided structures of the heart, which is commonly accompanied by a thick layer of fibroelastic tissue, termed endocardial fibroelastosis (EFE). Because human EFE develops only in fetal or neonatal hearts, and often in association with reduced blood flow, we sought to mimic these conditions by subjecting neonatal and 2-wk-old rat hearts to variations of the heterotopically transplanted heart model with either no intracavitary or normal flow and compare endocardium with human EFE tissue.. Hearts obtained from neonatal and 2-wk-old rats were heterotopically transplanted in young adult Lewis rats in a working (loaded) or nonworking (unloaded) mode. After 2-wk survival, hearts were explanted for histologic analysis by staining for collagen, elastin, and cellular elements. These sections were compared with human EFE tissue from HLHS.. EFE, consisting of collagen and elastin with scarce cellular and vascular components, developed only in neonatal unloaded transplanted hearts and displayed the same histopathologic findings as EFE from patients with HLHS. Loaded hearts and 2-wk-old hearts did not show these alterations.. This animal model for EFE will serve as a tool to study the mechanisms of EFE formation, such as fluid forces, in HLHS in a systematic manner. A better understanding of the underlying cause of the EFE formation in HLHS will help to develop novel treatment strategies to better preserve growth of the hypoplastic left ventricle.

Topics: Animals; Animals, Newborn; Collagen; Disease Models, Animal; Elastin; Endocardial Fibroelastosis; Heart Transplantation; Hemodynamics; Humans; Hypoplastic Left Heart Syndrome; Rats; Rats, Inbred Lew; Transplantation, Heterotopic

Topics: Adult; Elastic Tissue; Elastin; Endocardial Fibroelastosis; Endocardium; Heart Atria; Humans; Infant; Male; Microscopy, Electron; Muscle, Smooth; Myocardium; Myofibrils

Topics: Collagen; Elastic Tissue; Elastin; Endocardial Fibroelastosis; Environment; Female; Heart Rate; Humans; Infant; Male; Microscopy, Electron; Oxygen; Pressure