Pathogenic Hypothesis Of Human Atherosclerosis

Question 1

Name the 3 Hypothesis that try to explain the cause of atherosclerosis

Answer 1

1858 - Virchow - Reaction to Injury
1913 - Anitsckow - Lipid hypothesis
1973- Benditt - Monoclonal Hypothesis

Question 2

Describe the reaction to injury hypothesis

Answer 2

Atherosclerosis is the result of a healing response after injury, the result of cell proliferation and inflammation.
Accumulation of ECM, lipids and calcium were the result of these processes

Question 3

Describe (briefly) the lipid hypothesis

Answer 3

Anitsckow found that the element of animal fat that causes the disease is cholesterol.
He found that animals on a high fat diet develop more complicated lesions with cholesterol clefts (fibro-fatty lesions) and surrounding the clefts are necrotic cells and foam (lipid laden) cells.
He found that both mice with familial hypercholesteremia and mice med high fat diets had a similar phenotype

Question 4

What is X inactivation?

Answer 4

In females, only one X chromosome is active, the other is randomly inactivated

Question 5

What did Benditt notice upon closer observation of multifocal lesions in vessels?

Answer 5

That the expression of the isoform of G6PD was identical in the cells of the lesion (whilst 2 different isoforms were expressed in the cells if the media)

Question 6

By Benditt’s conclusion, what was the mechanism compatible with the monoclonal nature of atherosclerotic plaques?

Answer 6

Mutation - by chemical mutagens or viruses

Question 7

In reality, what may plaque clonality represent?

Answer 7

The expansion of preexisting patches of cells arising during development of the media