Vascular Endothelial Function And Atherosclerosis

Front 1

What are the normal epicardial coronary artery layers? (3)

Back 1

From out to in: adventitia, middle media (smooth m.) layer, intima layer (thin elastic and collagenous fibers and proteoglycans). The intima is lined by endothelium. Plaque grows on the endothelium.

Front 2

When the endothelium is healthy, factors are produced that favor vessel dilation and the inhibition of thrombosis, growth and inflammation. What is one such factor?

Back 2

Nitric oxide!

In normal vessels, when NO is infused, vasodilation occurs. In abnormal vessels, vasoconstriction occurs! Even in just the presence of just risk factors for atherosclerosis (increased LDL levels, increased BP, diabetes, smoking), the endothelium was abnormal and there was decreased ability of endothelium to produce NO.

Front 3

Nitric oxide is generated in the endothelial cell from the conversion fo ______ to nitric oxide by __________.

Back 3

L-arginine to Nitric oxide via nitric oxide synthase (eNOS).

Front 4

True or False:
Once produced, nitric oxide diffuses into the media of the vessel wall and acts on smooth muscle cells where it stimulates soluble guanylate cyclase to produce cyclic guanosine monophosphate 9cGMP) from GTP to cause smooth muscle relaxation and dilation of the artery.

Back 4

True!

Front 5

Nitric oxide also works on neighboring cells and not just the smooth muscle of the artery. What are its effects on the platelets, monocytes and endothelialcells nearby?

Back 5

For platelets: inhibits aggregation, adhesion and thus thrombosis
Monocytes: inhibits chemotaxis and activation
Endothelial cells: inhibits expression fo leukocyte adhesion cells

On smooth muscle, besides vasodilation, NO also inhibits mass proliferation this it is also an active anti-atherogenic molecule.

Front 6

One of the earliest changes associated with the presence of risk factors (increased LDL, increased BP, diabetes, smoking) is an increase in _________________ in the endothelial cell.

Back 6

oxidative stress

In the presence of risk factors the buffering capacity of the cell is exceeded and there is an increase in oxidant molecules. Oxidative stress results and is associated with an up-regulation of genes for factors or mediators that are proathrogenic. Importantly, one of em is a super oxide anion that inhibits nitric oxide! SInce nitric-oxide is known to be an anti-inflammatory, anti-thrombic, vasodilator, and inhibitor of growth, obviously inhibiting it is proathrogenic!

Front 7

_____________ is the earliest lesion in atherosclerosis. Accumulation of these results in a fatty streak in the intima.

Back 7

Foam cells (lipid laden macrophages)

These are oxidized lipoproteins taken up by macrophages - all within the intima.

Front 8

What does sheer stress have to do with localization of plaque in the vasculature?

Back 8

Locations of lesions in the proximal portions of arteries after branch points emphasize that low shear stress seems correlated with areas of plaque formation. Specifically, lower flow rates (reduced sheer stress) in lateral areas of bifurcation are where plaque typically occurs.