Added by: Mariam

I’m having trouble understanding the precise pathogenesis of atherosclerosis, and I don’t think the events in the book is well described, as the picture (fig. 9-10 p. 339) doesn’t quite corresponds with the description in the green box starting at page 338.

I am uncertain, when the fatty streak is formed, and when the smooth muscle cells comes into action. So my conclusion, as to when the different event occour, have come to this:

1. Damage to endothelial cells resulting in endothelial dysfunction
2. Accumulation of lipids in the intima layer
3. Lipids (LDL) are oxidized to oxLDL and cholesterol crystals by ROS which is provided by the macrophages
3. Adhesion of thrombocytes to the endothelial cells, and expression of VCAM-1 on the endothelial cells.
4. Adhesion of monocytes to the VCAM-1, migration to intima and differentiation to macrophages.
5. Macrophages starts to engulf oxLDL via scavenger receptors, resulting in accumulation of lipids in the macrophages now called foam cells. = fatty streak.
6. Thrombocytes, macrophages and cells in the vessel wall releases factors, that recruits the smooth muscle cells from media.
7. The smooth muscle cells is contributing to the phagocytosis of lipids, also by a scavenger receptors, resulting in SMC derived foam cells.
8. The smooth muscle cells proliferates, and produces fibrous tissue, resulting in the creating of a fibrous plaque (atherom).
When i’m looking at fig. 9-10 it looks like, the fatty streak is consisting of foam cells derived from macrophages as well as SMCs. However at page 340 in the orange “morphology” box, they describe the fatty streaks like this: “They are composed of lipid-filled foamy macrophages but are only minimally raised and do not cause any significant flow disturbance.”
So my questions are:
1) Are there any mistakes in the pathogenesis described above?

2) When exactly is the fatty streak formed?

3) Are the smooth muscle cells recruited after the creation of the fatty streak, or are they involved in the process of creating it?

4) Is it correct, that the foam cells are dead macrophages, and right before they die, they release cytokines that recruit more monocytes?

 

Added by: Alex