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Old 01-01-2010
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Arrow 1st step in pathogenesis of atherosclerosis caused by hyperlipidemia

This is a question i faced in USMLE Rx which I want to share with you guys.

As we all know, endothelial cell dysfunction is generally the 1st step in atherosclerosis.

But according to USMLERx, in the case of hyperlipidemia, LDL cholesterol oxidation is the 1st step in atherosclerosis.

What do you guys think? Agree/disagree?
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Old 01-01-2010
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according to robbins....

chronic endothelial injury is the first step followed by
accumulation of lipoprotein mainly LDL in the vessel wall, followed by
oxidation of lipoprotein,
adhesion of monocytes,
adhesion of macrophages,
trasformation into foam cells,
adhesion of platelets, and release of factors from platelets, maccrophages and vascular wall, leading to
SMC proliferation.....
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Old 01-01-2010
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The most acceptable theory of atherosclerosis formation follows this sequence:

1- Endothelial cell injury which can be due to several risk factors but the most important are hypertension, nicotin, immune mechanism and hyperlipidemia.
2- This injury leads to accumilation of plasma derived lipids and proteins leading to intimal thickening (atheroma).
3- This will lead to platelet adhesion to the surface of endothelial cells which leads to microthrombi formation and release of PDGF which attracts monocytes to the area.
4- Attracted monocytes become macrophages that engulf cholestrol (foam cells) and also secrete free radicals which causes oxidation of circulating LDL.
5- Oxidized LDL taken up by macrophages through scavenger receptor and this leads to extreme release of IL1 and TNF which inturn attract even more monocytes and stimulate smooth muscle cell and fibroblast proliferation.
6- Fibroblasts lay down collagen and elastin which aids in forming the mature atherosclerotic plaque.
7- Smooth muscles migrate from the media to the intima and transform into secretory cells producing collagen, elastin, IL1, TNF, PDGF, ..etc and serve as important mediators of the process.
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  #4  
Old 01-01-2010
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Ahh I see, thanks for sharing guys.
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