Cardiovascular disease is mainly caused by occlusion of the arteries, leading to impaired blood flow and thus a failing oxygen supply to the target organs. Prolonged oxygen deprivation leads to cell death in the target organs, such as the heart muscle (myocardium) or brain. The occlusion of the arteries is caused by a process called atherosclerosis. The following video of the pharmaceutical company Astrazeneca provides a detailed description of the atherosclerosis process in laymens terms. This presentation of the atherosclerosis process comes very close to the truth. In the text below I will try to explain what goes wrong in a bit more detail.
As can be deducted from the video, atherosclerosis is an inflammatory disease that leads to the buildup of plaque inside the walls of arteries. The actual cause of atherosclerosis is unknown, but it is believed to be initiated by inflammatory processes in the vessel wall. The process begins with dysfunction of the smooth layer of so-called endothelial cells that line the vessel wall. This mostly occurs at sites with slow or disturbed blood flow (e.g. sharp bends or branching of arteries) and is negatively influenced by high blood pressure and elevated blood glucose levels caused by diabetes. The dysfunctional endothelial cells are not able to correctly separate the blood from the underlying vessel wall tissue. As a result they allow low-density lipoprotein (LDL) molecules, the so-called “bad cholesterol”, from the bloodstream to penetrate the vessel wall. Subsequently a vicious inflammatory circle starts. Trapped LDL is oxidized due to the naturally occurring oxidative stress in the vessel wall. The body’s immune system recognizes this oxidized LDL as a foreign compound that does not belong in the vessel wall and responds by sending specialized white blood cells (monocytes) to clear these foreign compounds from the vessel wall. These monocytes infiltrate the vessel wall and absorb the oxidized-LDL, forming the so called foam cells (lipid loaded macrophages).
This is the point where the process goes awry. Due to natural limitations, the foam cells are unable to breakdown the oxidized LDL. As a result they continue to take-up oxidized LDL particles till they literally burst and undergo cell death (necrosis). As a natural defense system these dying foam cells excrete so-called chemo-attractants that attract more monocytes to clear the cell debris of these dead cells, just like any other dying human cell would do. However, these new monocytes still cannot breakdown the oxLDL, and undergo the same process, slowly expanding the plaque size. During this process the endothelial cells remain dysfunctional and new LDL molecules continue to accumulate in the vessel wall. During this process a necrotic core containing extracellular lipids and cell remnants slowly builds.
As atherosclerosis progresses, platelets, smooth muscle cells and other white blood cells (T- and B- lymphocytes and dendritic cells) also join the inflammatory reaction of the foam cells, expanding the plaque size even further. On top of that, this derailed inflammatory process also induces calcification of the arteries by inducing differentiation of vascular smooth muscle cells into bone forming cells called osteoblasts. This plaque growth and arterial calcification stiffens the vessel wall and narrows the lumen of a blood vessel which restricts blood flow leading to oxygen deprivation in target organs resulting in diseases like coronary or peripheral artery disease. Furthermore, plaque formation reduces the flexibility of arteries, leading to high blood pressure and thus even more dysfunctional endothelial cells. At a final stage the plaque surface may rupture, which can induce the formation of a blood clot (thrombus) that acutely blocks blood flow to downstream organs (e.g. the heart or the brain). This will result in ischemic stroke or Acute Myocardial Infarction (AMI). Atherosclerosis is usually asymptomatic until >50% occlusion of the artery or plaque rupture occurs.