Good summary of Robbins, bbydoc.
However, hyperlipidemia that's mentioned in the first step is not LDL oxidation. It's the direct damaging effect of lipids on the endothelium ('chemical irritation'). Essentially, first and second step is the same thing: Due to the chronic 'irritation' (damage/dysfunction) of endothelium, cytokines are released from endothelium. One of the key effects of cytokine is recruitment of monocytes to the intima of arteries. These monocytes transform into macrophages and macrophages themselves also secrete cytokines. Due to the effect of cytokines secreted by both endothelium and macrophages, LDL enters into intima and becomes oxidized. These oxidized LDL molecules are taken up by macrophages through their scavenger receptors, like you've mentioned in the other posts.
Here's an illustration from Robbins which I think clears this up:
Good luck in studying my friend.
Not to beat this thing to death, but LDL ox. does lead to endothelial cell dysfunction/injury, which is implied in this figure from robbins (i.e. hyperlipidemia-->endothelial cell injury/dysfunction), and further elucidated in the accompanying text.
It is easy to misinterpret the order of the events as indicated in the figure, which is why reading the text is informative, and clears all ambiguity.
Excerpt, pg 500 Robbins 8th Edition:
"With chronic
hyperlipidemia, lipoproteins accumulate in the intima. These lipids are
oxidized through the action of oxygen free radicals locally generated by macrophages or endothelial cells.
Oxidized LDL is ingeseted by macrophages through a
scavenger receptor, distinct from the LDL receptor, and accumulates in phagocytes, which are then called
foam cells. In addition,
oxidized LDL stimulates the release of growth factors, cytokines, and chemokines by endothelial cells and macrophages that increase monocyte recruitment into lesions. Finally,
oxidized LDL is cytotoxic to endothelial cells and smooth muscle cells and can induce endothelial cell dysfunction"
So, indeed, in the presence of hyperlipidemia, LDL ox does cause endothelial cell dysfunction and should thus be accounted for as a prior rather than subsequent event (although it occurs throughout the condition). Some of the confusion may lie in the fact that Robbins also states that hyperlipidemia can "impair endothelial function" by increasing local oxygen free radical production, but that this is more frequently seen in hypercholesterolemia, and doesn't impart frank cellular injury or dysfunction such as is seen with LDL oxidation.
Hope this helps.
