Atherosclerosis Flashcards
What is atherosclerosis?
A progressive disease that is caused by build up of cholesterol and calcim in the blood vessels, which can lead to its occlusion and other problems.
How can atherosclerosis lead to other cardiovascular problems?
It can lead to blockage or narrowing of blood vessels, which can cause less oxygen and nutrients to be delivered to certain parts of the body/heart.
What is the difference of vulnerable and stable plaques?
Stable plaques have a small lipid pool and a thick fibrous cap. It has a preserved lumen and is just narrowed.
Vulnerable plaques have a thin fibrous cap but a large lipid pool. There are lots of inflammatory cells and has a danger to rupture, which can cause a thrombus to form.
What are the 2 mechanisms of atherogenesis?
- Endothelial dysfunction and lipid accumulation
- Contribution of leukocytes
How does endothelial dysfunction and lipid accumulation lead to atherogenesis?
Endothelial dysfunctions when there is reduced or no NO production, which means less dilation
High LDL levels can cause endothelial dysfunction
Why is atherosclerosis an example of sterile inflammation?
It’s inflammation that is caused by the body as it is the problem. There is no pathogens that is causing the inflammation.
How does sterile and non-sterile inflammation differ?
For non-sterile inflammation, infection is introduced into the body and neutrophils eat the pathogens. Then, monocytes are recruited and they differentiate into M1 macrophages when in the tissue. The M1 macrophages eat the neutrophils. Then, the stromal cells deal with the damage caused by the inflammation response to repair the tissue. An M1 turns to an M2 to hold the information of the pathogen.
In sterile inflammation, a chronic inflammatory disease sends a persistent low-grade inflammatory response. This means there’s a persistent stimulus recruiting macrophages, which leads to amplification of inflammatory response and tissue damage.
How does sterile inflammation happen specifically during atherosclerosis?
There will be a persistent influx of monocytes that eat the cholesterol. Then, these M1s turn into foam cells = prodcues inflammatory cytokines = stimulates endothelial cells to let more monocytes in. Since foam cells can’t leave = necrosis of the foam cell = releases lipid when it dies. THis essentially means that cholesterol is just stuck under the endothelial layer.
What are the major risk factors for atherosclerosis?
Age, gender, family history, menopause
High LDL/low HDL, obesity, hypertension, smoking, inactivity, diet
How is LDL transported around the body?
LDL in the blood is detected by LDL receptors and brought into the liver by them.
What is the mechanism of action of statins?
Inhibits HMG-CoA reductase = up-regulates LDL receptors in liver = reduced serum LDL levels
= blocks RhoA synthesis = inhibits cell motility = cells don’t migrate towards atherosclerotic lesions
Reduces synthesis and secretion of lipoproteins from the liver
What are the effects of statins over time?
LDL lowered = endothelial function restored = reduced inflammation = less ischaemic episodes = stabilised vulnerable plaques = less vascular events
What are the side effects of statins?
- Increase in liver enzymes (as statins are metabolised in the liver)
- Headache, fatigue, GI intolerance, and flu-like symptoms
What are other drugs that are paired with statins?
Anti-platelets, beta-blockers, ACE inhibitors, CCBs, diuretics
What is the effect of statins on leukocyte migration?
Statins block RhoGTPases that are needed for leukocyte recruitment = inhibits leukocyte recruitment and inflammation
