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11. Biochemistry of blood vessels

Summary

  • The endothelium has many important roles, such as ECM production, oxidation of LDL, inflammation, and regulation of the vascular tone

This is a dry topic

Nitric oxide has many effects on vasculature and is produced by endothelial NO synthase. The effects are smooth muscle relaxation (vasodilation), inhibits thrombosis formation, inhibits leukocyte-endothelial cell adhesion, and inhibiting proliferation of smooth muscle cells. NO synthase needs calmodulin and calcium ions to work.

Endothelins are a family of 21 amino acid peptides that are strong vasoconstrictors. They also regulate cell proliferation and hormone production. One type in the family, ET1, is the most potent vasoconstrictor that we know. Endothelins can either bind to type A receptors in vascular smooth muscle and cardiac muscle where they activate phospholipase C alone, or they can bind to type B receptors in endothelium and smooth muscle where they activate phospholipase C while also inhibiting adenylyl cyclase.

Prostacyclin, a type of prostaglandin, is released from endothelium and acts on nearby cells (paracrine, like all eicosanoids). They bind to receptors on platelets and vascular smooth muscle to inhibit platelet activation and vasodilate, respectively. They’re not stored, but produced on demand.

Platelet activating factor, or PAF, is a phospholipid bound to the surface of endothelial cells. It has many functions, the most important of which is to recruit and bind leukocytes to the endothelium.

During inflammation, the endothelium plays and important role in allowing leukocytes to pass from the blood to the extracellular space through the endothelium. This process is called extravasation and requires many surface proteins such as integrins, selectins and others.

The selectin family is a family of three; E-selectin, L-selectin and P-selectin. The prefixes show where the types of selectins are found, on endothelial cells, leukocytes and platelets, respectively. E-selectin is only expressed during inflammation. L-selectin is constitutively (always) expressed. P-selectin is stored inside platelets (and endothelial cells actually). Upon activation, the selectins are moved to the cell surface.