Atherosclerosis is a chronic long terms asymptomatic disease that remains clinically silent for many decades. The initial causing agents are Low Density Lipoproteins (LDLP), the anatomical area affected are the arteries.
What is a LDLP?
LDLP's are small protein molecules which bind to fats making them soluble. The body is mainly made up of water including the main network of transport, the blood. The fat must be soluble in the plasma in order for it to be moved to cells and up-taken into the cell by receptor-mediated endocytosis (the process by which cells uptake fats).
What happens to LDLP's?
LDLP's circulate in the blood carrying lipids to various different cells. The problems occur when LDLP's penetrate the walls of the arteries. LDLP's vary in size from large molecules to much smaller ones. The smaller LDLP's are able to pass between the endothelial cells (those that line the artery lumen) into the extracellular space within the artery wall. In here these LDLP's become oxidised, when oxidised they bind to the proteoglycans, the material that occupies the extracellular space providing support to surrounding cells. When LDLP's
How does the artery wall respond?
The accumulation of oxidised LDLP's triggers signalling pathways associated with the inflammatory response. The accumulation of monocytes in the localised area. These penetrate the gaps between the endothelial cells into the extracellular matrix where they differentiate into macrophages (sells which consume biological mass to aid in its disposal). Macrophages uptake the LDLP's becoming foam cells. Foam cells are LDLP filled macrophages, foam cells recruit High Density Lipoproteins (HDLP) to help remove lipids form the artery walls. Over time, the acclamation of foam cells within the artery extracellular matrix begins to 'snowball', more foam cells means more mass accumulating in the wall of the artery. The blood vessel muscle stretches to accommodate the build up of foam cells, the endothelial cell lining also thickens, the thickening of the intima (muscle layer) causes the plaque to become capped and is now referred to as an atheroma. This narrows the blood vessel lumen as it grows in mass as well as distorts the natural elasticity of the blood vessel, causing a reduction in its stretch capacity during systolic contraction. Overtime the atheroma will release enzymes which causes the walls of the arteries to ballon accommodating for the atheroma and the narrowing of the artery.
As the atheroma ages, the LDLP's along with the cell membrane of the foam cells causes cholesterol (a vital component offering rigidity to cell membranes and transported in LDLP's) to leak into its core, this along with calcium from ruptured foam cells leads to calcification of the plaque. The plaque will remain asymptotic for may years, a rupturing of the plaque will trigger coagulation factors to clot this can rapidly escalate to form a blood clot, this process causes 'stenosis' or narrowing of lumen. Unstable clots can break off which can go on to obstruct the blood vessels leading to myocardial infarction or heart attack.
Diet as a risk factor
There is no clear link between fat intake and the onset of atherosclerosis, there is a sound scientific argument that high levels of cholesterol can be a factor as cholesterol is carried in LDLP's throughout the bloodstream. Elevated circulating cholesterol can trigger increased levels of LDLP's -the causing agent of atherosclerosis.