Larger blood vessels share a common three-layered structure. Figure 4a illustrates the arrangement of these layers, or tunics, in a muscular artery.

A thin inner layer, the tunica intima, comprises an endothelial cell monolayer (endothelium) supported by connective tissue. The endothelial cells lining the vascular lumen are sealed to each other by tight junctions, which restrict the diffusion of large molecules across the endothelium. The endothelial cells have a crucial role in controlling vascular permeability, vasoconstriction, angiogenesis (growth of new blood vessels) and regulation of haemostasis. The intima is relatively thicker in larger arteries, and contains some smooth muscle cells in large and medium-sized arteries and veins.

The thick middle layer, the tunica media, is separated from the intima by a fenestrated (perforated) sheath, the internal elastic lamina, mostly composed of elastin. The media contains smooth muscle cells embedded in an extracellular matrix (ECM) composed mainly of collagen, elastin and proteoglycans. The cells are shaped like elongated and irregular spindles or cylinders with tapering ends, and are 15–100 µm long. In the arterial system, they are orientated circularly or in a low-pitch spiral, so that the vascular lumen narrows when they contract. Individual cells are long enough to wrap around small arterioles several times.

Adjacent smooth muscle cells form gap junctions. These are areas of close cellular contact in which arrays of large channels called connexons span both cell membranes, allowing ions to flow from one cell to another. The smooth muscle cells therefore form a syncytium, in which depolarization spreads from each cell to its neighbours.

An external elastic lamina separates the tunica media from the outer layer, the tunica adventitia. This contains collagenous tissue supporting fibroblasts and nerves. In large arteries and veins, the adventitia contains vasa vasorum, small blood vessels that also penetrate into the outer portion of the media and supply the vascular wall with oxygen and nutrients.

These three layers are also present in the venous system, but are less distinct. Compared with arteries, veins have a thinner tunica media containing a smaller amount of smooth muscle cells, which also tend to have a more random orientation.

The protein elastin

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