Process of Atherosclerosis and Thrombosis

A blood vessel (artery or vein) wall has three layers.

• Tunica intima (inner layer)
• Tunica media (middle layer)
• Tunica adventitia (outer layer)

Tunica intima contains a single layer of cells known as endothelium, which forms the lining of the blood vessel. Tunica media mainly consists of smooth muscles, which regulate the calibre of the blood vessels. Tunica adventitia basically has connective tissues. Atherosclerosis is a formation of fatty deposits in the arterial wall. A fatty deposit is known as an atheroma or an atheromatous plaque.

Atherosclerosis is a complex inflammatory process characterised by deposition of fat, macrophages, and smooth muscles in the tunica intima. Usually, the endothelium maintains vascular integrity (keeps up the inner side of the artery smooth and toned) and homeostasis. Endothelial dysfunction or injury initiates the process of atherosclerosis.


Causes of endothelial dysfunction or injury

• Mechanical shear stresses (e.g. hypertension)
• Biochemical abnormalities (e.g. elevated blood low-density lipoprotein/LDL, elevated blood homocysteine, diabetes mellitus, obesity, excessive alcohol intake)
• Immunological factors (e.g. free radicals from cigarette smoking)
• Infections and inflammation (e.g. Helicobacter pylori and Chlamydia pneumoniae infections)
• Genetic factors (family history)

Endothelial dysfunction or injury increases the permeability (the ability to cross) to and deposition of LDL cholesterol in the tunica intima (inner layer). Macrophages flow in to digest the cholesterol. Accumulation of LDL cholesterol and macrophages form flat yellow lines or dots on the endothelium. They are known as fatty streaks and build transitional plaque.

This process stimulates secretion of inflammatory mediators (chemicals) by macrophages, monocytes, or damaged endothelium. These chemicals promote further accumulation of macrophages as well as migration and proliferation of smooth muscle cells. The proliferation of smooth muscle thickens the atheromatous plaque/atheroma. Smooth muscle cells produce and secrete a type of proteins known as collagen in large amounts. This stage is known as advanced atheromatous plaque. It grows slowly and narrows the lumen of the artery gradually. Larger atheromatous plaques become unstable. Therefore, they may stimulate the formation of a blood clot over the plaque (thrombosis) obstructing the blood flow partially or completely in the artery. Now, it is a complicated plaque.

Superficial endothelial injury may expose collagen, which stimulates platelet cell activation and adhesion, hence blood clot formation (thrombosis) over the plaque. Sometimes, an advanced plaque may rupture because, it is unstable. Therefore, blood can enter the inside of the ruptured plaque. Substances in the plaque stimulate thrombosis. Thrombus grows and obstructs the lumen of the artery gradually.


Related Links:

What Is Ischaemic Heart Disease?
Complications of Atherosclerosis
Introduction: Risk Factors of Atherosclerosis
Non-modifiable Risk Factors of CAD
Modifiable Risk Factors of CAD
Other Risk Factors of CAD
Cardiovascular Disease (CVD) Prevention Policy