Atherosclerosis as main cause of cardiovascular disease
Atherosclerosis is the major risk factor contributing to mortality and morbidity due to cardiovascular disease.

Molecular mechanisms underlying atherosclerotic plaque development
One of the initiating steps is the accumulation of lipoproteins (mainly VLDL and LDL) in the vessel wall where they can become modified. These modifications can be either enzymatic or non-enzymatic. Examples of enzymes involved are myoloperoxidase, lipoxygenase and phospholipases. After modification, LDL is pro-inflammatory and attracts circulating monocytes. These monocytes migrate from the circulation into the vessel wall and differentiate into macrophages. The modified LDL is taken up by macrophages through scavenger receptor pathway and this process eventually leads to foam cell formation. The accumulation of foam cells in the vessel wall is called the fatty streak, the first stage in atherogenesis. The diverse array of cytokines and growth factors that are locally produced by macrophages, endothelium and smooth muscle cells attracts more cells into the lesion and leads to smooth muscle cell proliferation. This results in the formation of a more advanced fibrous plaque, covered by a dense cap of connective tissue. Under the fibrous cap, smooth muscle cells together with fat laden macrophages, T-lymphocytes, necrotic debris, cholesterol clefts and mineralisation can be found. These severe lesions partially occlude the vessel wall and may impair blood flow. Most of the sudden deaths by myocardial infarction are due the rupture or fissure of these lesions.