Below are some of the steps proposed to be involved in atherosclerosis. Based on

Question

Below are some of the steps proposed to be involved in atherosclerosis. Based on lecture and the papers we went over, place the following steps in order.

a.)Monocytes bind to cell surface receptors and are internalized to a layer underlying the endothelial layer

b.)PECAM1, a cell adhesion molecule experiences tension in high probability regions of the heart causing differential gene expression in these cells compared to low probability regions

c.)NFKB is expressed but inhibited in the cytoplasm of endothelial cells of high probability regions.

d.)Smooth muscle cells and extracellular matrix proteins migrate to the damaged area and form a fibrous cap.

e.)NFKB’s nuclear localization signal is exposed, it binds to an importin and is transported into the nucleus where it activates genes involved in the inflammatory response.

f.)An irritant causes damage in the endothelial lining of high probability regions of the heart.

g.)Monocytes mature into macrophages and begin to ‘eat’ or clean up the damaged area (dead cells, fat, toxins etc) until they die and become foam cells.

h.)IKB is phosphorylated and targeted for degradation.

Explanation / Answer

a,c,b,e,g,d,f,h- Probably this is the sequence.

Atherosclerotic plaque formation involves 5 steps: 1. low density lipoprotein (LDL) accumulation in the intima; 2. oxidation of LDL; 3. recruitment of monocytes-macrophages; 4. uptake of oxidized LDL by macrophage scavenger receptors, and transformation of macrophages into foam cells; 5. formation of a fibrous cap containing smooth muscle cells, which permits stabilization of the plaque. At each step of this process, inflammatory cytokines are implicated making the atherosclerotic process a chronic inflammatory disease.

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