Flow control in our vessels: vascular valves make sure there is no way back
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Cellular and Molecular Life Sciences
REVIEW
Flow control in our vessels: vascular valves make sure there is no way back Eleni Bazigou • Taija Makinen
Received: 28 June 2012 / Revised: 24 July 2012 / Accepted: 26 July 2012 / Published online: 25 August 2012 Ó The Author(s) 2012. This article is published with open access at Springerlink.com
Abstract The efficient transport of blood and lymph relies on competent intraluminal valves that ensure unidirectional fluid flow through the vessels. In the lymphatic vessels, lack of luminal valves causes reflux of lymph and can lead to lymphedema, while dysfunction of venous valves is associated with venous hypertension, varicose veins, and thrombosis that can lead to edema and ulcerations. Despite their clinical importance, the mechanisms that regulate valve formation are poorly understood and have only recently begun to be characterized. Here, we discuss new findings regarding the development of venous and lymphatic valves that indicate the involvement of common molecular mechanisms in regulating valve formation in different vascular beds. Keywords Valve Lymphatic vessel Vein Endothelium Morphogenesis
Control of fluid flow through the vascular system: importance of valves The circulatory system is composed of the heart and the blood vessels, which distribute nutrients, hormones, gases,
E. Bazigou T. Makinen (&) Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK e-mail: [email protected] Present Address: E. Bazigou Cardiovascular Mechanics Lab, Department of Bioengineering, Imperial College London, London SW7 2AZ, UK e-mail: [email protected]
and metabolic waste products in the body, and the lymphatic vessels that ensure that the extravasated fluid and proteins are drained from the tissues and transported back to the blood circulation. The beating of the heart generates pulsatile flow of blood that is pushed through a hierarchical network of arteries, capillaries, and veins, with heart valves controlling the flow of blood through the heart by opening and closing during the contractions of the heart. In addition, contraction of skeletal muscles compresses the walls of deep veins and drives the movement of blood inside the vessels, thus behaving like peripheral muscle pumps [1]. Additional mechanisms that activate the venous pumping system include arterial pulsation and the ankle joint pump, which is generated by ankle joint motion [2], while luminal valves in the veins ensure unidirectional blood flow (reviewed in [3]). Venous valves are required for efficient return of blood particularly from lower extremities, where the greatest gravitational forces are present. Like the blood vasculature, the lymphatic system is composed of a hierarchy of vessels with specific features serving their unique functions: the blind-ended lymphatic capillaries (also called initial lymphatics) that absorb the interstitial fluid and the collecting lymphatic vessels that transport the lymph to t
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