Arterial Biology in the Healthy PatientEdit
Normal arteries are comprised of three layers. The intima is the layer closest to the arterial lumen; it is comprised of a single layer of endothelial cells and functions both metabolically and mechanically as a barrier. The media is located immediately outside the intima, separated by the internal elastic lamina (an elastin-rich boundary). It is composed mainly of smooth muscle cells (and their associated extracellular matrix) and is the thickest layer of the arterial wall. The media functions as the elastic and contractile unit of the arterial wall. The adventitia, which is the outermost layer of the arterial wall, contains nerves, lymphatics, and where applicable, the vasa vasorum.
The intima consists of tightly abutted endothelial cells. In the unactivated state, the mechanical arrangement of intimal cells prevents large molecules form traversing to the subintimal layer. The quiescent endothelium functions biochemically to maintain anticoagulation (e.g. heparan sulfate, prostacyclin), vasodilation, immunomodulation (inhibition of leukocyte adhesion) and prevention of medial smooth-muscle proliferation. In the activated state, however, intimal cells facilitate adhesion and diapedesis of leukocytes, they promote inflammation, fail to inhibit vasoconstriction, and are thrombogenic.
The media, composed of smooth muscle cells and their extracellular matrix, is the largest component of the artery (radially speaking).
Smooth muscle cells in the media function synthetically and mechanically. The smooth muscle cells produce the extracellular matrix via collagen, elastin, and proteoglycans. Furthermore, the smooth muscle cells synthesize inflammatory mediators such as interleukin-6 and tumor necrosis factor-alpha. As we will discuss below, synthetic function of vascular smooth muscle cells is exaggerated at sites of atherosclerosis.
Mechanical function of smooth muscle cells is influenced by sympathetic neural stimulation, endothelial derived factors (e.g. nitric oxide), and circulating chemicals (e.g. angiotensin II, vasopressin, epinephrine, adenosine, etc.).
Arterial Biology in the Atherosclerotic Disease ProcessEdit
The general progression of atherosclerotic disease is as follows: (1) endothelial dysfunction, (2) lipid accumulation within the subendothelial space, (3) leukocyte and smooth muscle recruitment to the subendothelial space, (4) foam cell formation, (5) expansion of extracellular matrix within the plaque proper.