It is a process occurring in the walls of large and medium sized elastic arteries where an irregular thickening of the wall occurs, due to deposition of lipids, smooth muscles, connective tissues and other cells. Lesion is called an atheroma and the process is called atherosclerosis. There are several theories to explain how this process occurs. Out of them, the,”REACTION TO INJURY”, theory is the most accepted one.
There are so many ways, which I have mentioned later, where endothelium of the vessel can get damaged or injured. Once an endothelium is injured, it leads to secretion of various cytokines which would activate platelets and also it would increase the expression of VCAM-1 where platelet adhesion will take place. Mean while lipids will also get accumulated. Accumulated lipids will get oxidized producing oxidative species. When lipoproteins, specially LOW DENSITY LIPOPROTEINS (LDL) get accumulated, they will be altered by the oxidative species generated.
While all these are going on damaged endothelial cells will secrete cytokines which would stimulate Monocytes to migrate into intima. Ingestion of altered lipo proteins will make them to loose their function and become FOAM cells.
With the activation of T cells, various cytokines will be released (Eg:- IFN- gamma) which would in turn stimulate macrophages, endothelial cells and smooth muscle cells. Then from these cells who got activated various cytokines ( Eg:- PDGF, FGF,TGF-alpha) will be released where they recruit smooth muscle precursor cells into intima, from either media or from circulating precursors. Ultimately smooth muscle cell proliferation, along with connective tissue proliferation and deposition of lipids both extracellular and extracellular will occur.
Endothelial cell damage may due to;
- Mechanical and hemodynamic stress
- sheer stress ( hypertension)
- Branching points at the arteries
Risk factors for atherosclerosis are mainly two folds;
- Major risk factors
- Modifiable factors
- Cigarette smoking
- C- reactive protein
- Non-modifiable factors
- Increasing age
- Male gender
- Family history
- Genetic abnormalities
- Modifiable factors
- Minor risk factors
- Physical inactivity
- High carbohydrate Intake
- Trans Unsaturated fat intake
- Infections – CMV, Chlamydia, HSV