Intraluminal valves: development, function and disease

• Published in: Disease models & mechanisms Vol. 10; no. 11; pp. 1273 - 1287
• Main Authors: Geng, Xin, Cha, Boksik, Mahamud, Md Riaj, Srinivasan, R Sathish
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01.11.2017; The Company of Biologists
• Subjects: Animals; Blood vessels; Calcific aortic valve disease; Calcification; Disease prevention; Edema; Embolisms; Genetic Predisposition to Disease; Heart; Heart Valve Diseases - genetics; Heart Valve Diseases - pathology; Heart Valves - physiology; Humans; Inflammation; Leg ulcers; Lymphatic vasculature; Lymphedema; Mechanobiology; Models, Biological; Mutation; Prostheses; Pulmonary arteries; Review; Shear stress; Stress, Mechanical; Thrombosis; Transcription factors; Valves; Veins & arteries; Wnt/β-catenin signaling; Wnt/β-catenin signaling; Valves; Lymphatic vasculature; Calcific aortic valve disease; Mechanobiology
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.030825

The circulatory system consists of the heart, blood vessels and lymphatic vessels, which function in parallel to provide nutrients and remove waste from the body. Vascular function depends on valves, which regulate unidirectional fluid flow against gravitational and pressure gradients. Severe valve disorders can cause mortality and some are associated with severe morbidity. Although cardiac valve defects can be treated by valve replacement surgery, no treatment is currently available for valve disorders of the veins and lymphatics. Thus, a better understanding of valves, their development and the progression of valve disease is warranted. In the past decade, molecules that are important for vascular function in humans have been identified, with mouse studies also providing new insights into valve formation and function. Intriguing similarities have recently emerged between the different types of valves concerning their molecular identity, architecture and development. Shear stress generated by fluid flow has also been shown to regulate endothelial cell identity in valves. Here, we review our current understanding of valve development with an emphasis on its mechanobiology and significance to human health, and highlight unanswered questions and translational opportunities.