Mechanisms of atheroma and infarction Flashcards
What is an atheroma and what does it cause?
Degeneration of the walls of the arteries caused by accumulated fatty deposits and scar
tissue, and leading to the restriction of the circulation and a risk of thrombosis
What is infarction?
Obstruction of the blood supply to an organ or region of tissue, typically by a
thrombus or embolus, causing local death of the tissue
What do lipoproteins transfer and why?
Lipoproteins transfer fats around the body so they are available to be taken up by the
cells via receptor-mediated endocytosis
What do the lipids carried by LDL’s include?
The lipids carried by LDLs include cholesterol, phospholipids, and triglycerides
What type of response is atherosclerosis?
A complex inflammatory process
What is atherosclerosis mediated by?
Mediated by LDL & angiotensin II
What are common sites of atherosclerosis?
- Carotid arteries & Circle of Willis
- Coronary arteries
- Iliac arteries
- Aorta
Steps involved in initiation
1) Inflammatory triggers active arterial endothelial cells
a. Oxidation of LDL particles, chiefly stimulated by the presence of necrotic cell debris and free radicals in the endothelium
2) LDL and inflammation
a. Endothelial cells start to become activated and express cytokines and adhesion molecules
3) Circulating monocytes bind to the activated endothelium
a. They start expressing adhesion molecules and begin to move through the tissue and reside in the intimal layer
4) Monocytes differentiate into tissue macrophages which release their own inflammatory mediators
a. It is an appropriate immunological response to inflammation but in the wrong place here
Steps involved in plaque formation
1) Macrophages then begin to accumulate LDL from the circulation and become foam cells
2) Activated foam cells release other growth factors which cause smooth muscle cells to leave the medial layer and cross the internal elastic lamina entering the intima
3) The activated smooth muscle cells also release growth factors and may also begin synthesising collagen and elastin in the intima layer
Steps involved in the maturation of the plaque
1) Smooth muscle cells accumulate LDL becoming a second type of foam cell but they continue to make an extracellular matrix of elastin and collagen which forms a fibrous plaque
2) Cells underneath this plaque become oxygen starved
a. They begin to undergo apoptosis and release their fat which forms a globule of fat that is now accumulating in the intima, known as the lipid core
3) The dying cells release matrix metalloproteases and other enzymes which can break down the fibrous matrix towards the edge of the plaque leaving a large lipid core covered by a fibrous plaque that may be vulnerable to enzymatic digestion
What is the role of calcium deposits or what arguments remain?
- The role of calcium deposits remains uncertain
o There have been arguments that calcification may actually stabilise the plaque
What can occur if the central core becomes too large?
- If the central core becomes too large, a large plaque can occur and the sub-endothelium is exposed
What is the endothelium usually?
- The endothelium is normally an anticoagulant surface
What does collagen form and where and gives us what?
- Collagen forms very good bases for clotting along with other proteins and factors in the intima
o This gives us a pro-coagulant surface in an artery
Consequences of atheromas(Occlusive thrombosis)
- E.g. myocardial infarction
o Commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle
