Blood Vessels

The endothelium consists of a single, thin layer of flattened cells lining the arterial wall. Endothelial cells are the first barrier between the blood and the extravascular space. As the gatekeeper of the blood vessel wall the vascular endothelium is an important source of mediators. These mediators maintain an anti-thrombotic surface, regulate vascular tone, modulate inflammatory responses, and inhibit proliferation of vascular smooth muscle cells.

Nitric oxide and prostacyclin are mediators that enhance endothelial function.  Angiotensin II and thomboxane A2 are mediators that contribute to endothelial dysfunction.

The endothelium functions to regulate vascular tone by releasing endothelium derived relaxing and contracting factors.  Nitric oxide is a key relaxing factor that promotes vasodilation. In addition, nitric oxide helps maintain endothelial integrity because it inhibits platelet activity, vascular smooth muscle cell growth and adhesion of inflammatory cells to the endothelial surface. Any inactivation of nitric oxide contributes to endothelial dysfunction.

Cardiovascular risk factors such as elevated low density lipoprotein cholesterol (LDL), low concentrations of high density lipoprotein (HDL), insulin resistance, obesity, hypertension and smoking  lead to a cellular events that cause endothelial dysfunction which results  in endothelial injury. This arterial injury stimulates an inflammatory response.

The adhesion of circulating monocytes (white blood cells) to the surface of intact endothelial cells is an early event in the development of atherosclerotic lesions. After adhesion, monocytes insinuate (snuggle) themselves between the endothelial cells and the sub endothelial space.

Through the process of phagocytosis, monocytes are transformed into macrophages in which they ingest oxidized lipids. Cholesterol engorged macrophages take on a foamy appearance, and are referred to as “foam cells”. This initiates a fatty streak or atherosclerotic lesion. Additionally, when macrophages ingest oxidized LDL the (lysosomal) enzymes produce a respiratory burst. This generates a deluge of free radicals (oxidative stress) which depletes bio-available nitric oxide and generates cellular damage. Reduction of nitric oxide causes a loss in the protective and regulatory function of the endothelium.

A Key Point: macrophages only ingest oxidized/decayed LDL cholesterol. As such, reducing oxidation is essential to vascular integrity.

High HDL concentrations, the use of statins, low dose transdermal estrogen replacment, antioxidant foods and antioxidant supplements such as Vitamin C and E reduce the oxidation of LDL cholesterol.