Molecular and developmental mechanisms of congenital heart valve disease

Abstract

Congenital heart disease occurs in approximately 1% of all live births and includes structural abnormalities of the heart valves. However, this statistic underestimates congenital valve lesions, such as bicuspic aortic valve (BAV) and mitral valve prolapse (MVP), that typically become apparent later in life as progressive valve dysfunction and disease. At present, the standard treatment for valve disease is replacement, and approximately 95,000 surgical procedures are performed each year in the United States. The most common forms of congenital valve disease include abnormal valve cusp morphogenesis, as in the case of BAV, or defects in extracellular matrix (ECM) organization and homeostasis, as occurs in MVP. The etiology of these common valve diseases is largely unknown. However, the study of murine and avian model systems, along with human genetic linkage studies, have led to the identification of genes and regulatory processes that contribute to valve structural malformations and disease. This review focuses on the current understanding and therapeutic implications of molecular regulatory pathways that control valve development and contribute to valve disease.

The role of tenascin-C and oxidative stress in rheumatic and congenital heart valve diseases: an observational study

“…The pathogenesis of rheumatic HVD is complex and involves genetic factors that predispose a person to the development of autoimmune reactions (4,5). The relationship between heart valve damage and the pathogenesis of valve fibrosis with immuno-inflammatory response is well known (1,2). Degenerative valve lesions have many features that are characteristic to active pathobiological processes, including chronic inflammation, lipoprotein deposition, active calcification, and activation of the renin-angiotensin system.…”

“…Degenerative valve lesions have many features that are characteristic to active pathobiological processes, including chronic inflammation, lipoprotein deposition, active calcification, and activation of the renin-angiotensin system. The course of rheumatic carditis is characterized by the expression of immunological and biochemical disorders (1,2,5,26). Increased expression of TnC has shown to be positively linked to a range of other cardiovascular pathologies, including acute myocardial infarction, atherosclerosis, pulmonary artery hypertension, neovascularization, the peri-infarct repair process following stroke, angiotensin II-induced cardiac fibrosis, vasospasm following subarachnoid hemorrhage, and vascular calcification etc.…”

“…HVD is caused by the interaction of several risk factors, such as genetic, autoimmune, inflammatory, infectious, and oxidative stress (1)(2)(3)(4). Acute rheumatic carditis is an important healthcare problem in developing countries and continues to be the leading cause of acquired heart disease in children worldwide, and acute rheumatic fever (ARF) occurs as a complication of an untreated group A β-hemolytic streptococcal pharyngitis (4,5).…”

Histone Deacetylase 3 Coordinates Deacetylase-independent Epigenetic Silencing of Transforming Growth Factor-β1 (TGF-β1) to Orchestrate Second Heart Field Development

“…3, G and H). Remodeling of the semilunar valves is associated with an increase in apoptosis (18). Hdac3…”

Molecular Mechanisms of Heart Valve Development and Disease

“…The semilunar and atrioventricular (AV) valves of the heart are made up of highly organized extracellular matrix (ECM) layers populated by quiescent valve interstitial cells (VICs) [1]. In healthy valves, the ECM is compartmentalized into layers composed of collagens, proteoglycans, and elastin, which are maintained by the VICs for proper valve function throughout life (Reviewed in [2]).…”