Molecular Pathophysiology
Atherosclerosis, metabolism and nuclear receptors – De Vries
Atherosclerosis = formation of lesion (=plaque) in blood vessels, consisting of dead cells, cholesterol,
cholesteryl esters, triglycerides, macrophages, smooth muscle cells, crystallized calcium > narrowing
vessels
Atherosclerosis is the underlying pathology of myocardial and cerebral infarction
When there are high LDL levels in the blood circulation:
- Monocytes are attracted by endothelial cells to clean up LDL
- Monocytes (in blood) go into tissue and become macrophages (=monocytes in tissue)
- LDL is a little oxidized by radical oxygen species (ROS)
- Macrophages can take up oxidized LDL
- Macrophages cannot handle all the LDL and become ‘foam cells’
- Macrophages secrete cytokines > inflammation and attraction of more monocytes
- Macrophages also secrete growth factors > smooth muscle cells (SMCs) differentiate and can
now migrate to endothelial cells > enlarge the lesion
, Multi-factorial disease and treatment:
- Environment: smoking, diet, lack of exercise > can be prevented
- Risk factors:
High cholesterol (LDL) > statins (to decrease cholesterol synthesis and upregulate LDL
receptors)
Low HDL
Hypertension > multiple drugs
Diabetes > insulin (in Diabetes type I)
- Genetic components
Familiar Hypercholesterolemia (FH) > LDL receptor gene mutation
Tangier disease > ABCA1 receptor defect
‘Genetic predisposition’ > multiple genes
Acute myocardial infarction: atherosclerosis in coronary artery > plaque rupture > formation of
thrombus that can obstruct the coronary artery, which results in decreased or no blood flow = infarction
Cells involved in atherosclerosis: monocytes/macrophages, T cells, endothelial cells, smooth muscle
cells
Treatment of atherosclerosis: stent in coronary artery > metal thing in which a balloon can be pumped
up to widen narrowed or obstructed vessels (angioplasty) (stent ensures that the vessel remains open)
Atherosclerosis, metabolism and nuclear receptors – De Vries
Atherosclerosis = formation of lesion (=plaque) in blood vessels, consisting of dead cells, cholesterol,
cholesteryl esters, triglycerides, macrophages, smooth muscle cells, crystallized calcium > narrowing
vessels
Atherosclerosis is the underlying pathology of myocardial and cerebral infarction
When there are high LDL levels in the blood circulation:
- Monocytes are attracted by endothelial cells to clean up LDL
- Monocytes (in blood) go into tissue and become macrophages (=monocytes in tissue)
- LDL is a little oxidized by radical oxygen species (ROS)
- Macrophages can take up oxidized LDL
- Macrophages cannot handle all the LDL and become ‘foam cells’
- Macrophages secrete cytokines > inflammation and attraction of more monocytes
- Macrophages also secrete growth factors > smooth muscle cells (SMCs) differentiate and can
now migrate to endothelial cells > enlarge the lesion
, Multi-factorial disease and treatment:
- Environment: smoking, diet, lack of exercise > can be prevented
- Risk factors:
High cholesterol (LDL) > statins (to decrease cholesterol synthesis and upregulate LDL
receptors)
Low HDL
Hypertension > multiple drugs
Diabetes > insulin (in Diabetes type I)
- Genetic components
Familiar Hypercholesterolemia (FH) > LDL receptor gene mutation
Tangier disease > ABCA1 receptor defect
‘Genetic predisposition’ > multiple genes
Acute myocardial infarction: atherosclerosis in coronary artery > plaque rupture > formation of
thrombus that can obstruct the coronary artery, which results in decreased or no blood flow = infarction
Cells involved in atherosclerosis: monocytes/macrophages, T cells, endothelial cells, smooth muscle
cells
Treatment of atherosclerosis: stent in coronary artery > metal thing in which a balloon can be pumped
up to widen narrowed or obstructed vessels (angioplasty) (stent ensures that the vessel remains open)
