Question

In atherosclerosis, the following process happens:

1.Lipid deposits of LDL-cholesterol happen on the endothelium
2.They triggers an inflammatory reaction of the endothelium: macrophages circulating in the bloodstream comes in and assimilates the LDL-cholesterol
3.The macrophage enters apoptosis when they are full of LDL-cholesterol, and this triggers collagen production which ends in creating a plaque
My question is: in a common inflammatory reaction, the secretion of caspase triggers the apoptosis of the macrophages that have assimilated foreign material. Then the macrophages migrate to lysosomes where they are degraded. Why does this migration not happen in atherosclerosis?

Might be linked with this question: Why oxLDL accumulate to form foam cells?

Answer 1

In atherosclerosis, macrophages engorged with oxidized LDL become foam cells and fail to undergo apoptosis and clearance due to disrupted regulatory mechanisms. This leads to accumulation of dead cells and plaque growth. Risk factors like high cholesterol and smoking can worsen this process.

Step-by-step explanation:

Atherosclerosis and Foam Cell Formation

In atherosclerosis, low-density lipoproteins (LDL) accumulate in the arterial wall's endothelium, initiating an inflammatory response. This leads to the migration of macrophages which engulf the oxidized LDL, forming foam cells. The question raised pertains to why macrophages in atherosclerosis do not undergo apoptosis and migrate to lysosomes for degradation as they would in typical inflammatory responses. This might be linked to foam cell formation; macrophages engorged with oxidized LDL (oxLDL) become dysfunctional and are unable to process the lipids efficiently. As a result, instead of undergoing regular apoptosis and clearance, these cells accumulate, dying within the arterial wall and contributing to plaque formation.

Risk factors such as hypertension, high cholesterol, diabetes, and smoking can exacerbate this process. Unlike caspases in normal inflammation, the continued presence of oxLDL and other stress factors in the arterial wall may disrupt the regulatory apoptosis mechanisms, preventing macrophage clearance and leading to the growth of the atherosclerotic plaque.

oxLDL is particularly problematic because it continues to attract macrophages and perpetuates the cycle of foam cell formation and death, leading to plaque growth and arterial blockage which can cause severe cardiovascular events like heart attacks or strokes.