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Recommended video: Coronary arteries and cardiac veins [11:41]
Overview of the main coronary arteries and cardiac veins.

Atherosclerosis is the thickening and loss of elasticity of arterial walls as a result of invasion and accumulation of white blood cells and proliferation of intimal smooth muscle cells that create a fibrofatty plaque.

Atherosclerosis, also known as arteriosclerotic vascular disease, is a type of arteriosclerosis.

Other types of arteriosclerosis include:

  • Monckeberg’s arteriosclerosis,
  • hyperplastic arteriosclerosis and
  • hyaline-type arteriosclerosis.

Atherosclerosis is thus a syndrome affecting arterial blood vessels due to a chronic inflammatory response in the artery walls. While atherosclerosis often remains asymptomatic for decades, it can increase the risk of local thrombosis and distal embolization that can present clinically as myocardial infarction or stroke.

  1. Anatomy of arteries
  2. Pathogenesis
  3. Clinical notes
  4. Sources
+ Show all
Inner circular smooth muscle layer (histological slide)

Anatomy of arteries

Artery (histological slide)

Vessel walls of arteries and veins are organized into 3 concentric, similar layers:

  • the tunica intima,
  • the media and,
  • the adventitia.

However, the middle layer (tunica media) is thicker in arteries than in veins.

Tunica intima of artery (histological slide)

The tunica intima is the innermost and thinnest layer, consisting of a monolayer of simple squamous endothelial cells on top of a basement membrane with minimal underlying extracellular matrix (ECM). The intima is separated from the next layer by a dense elastic membrane called the internal elastic lamina, which are circularly arranged bands.

Tunica media of artery (histological slide)

The tunica media is the thickest layer of the arteries, and is composed predominantly of smooth muscle cells and ECM, surrounded by loose connective tissue , nerve fibers, and smaller vessels of the adventitia. Separating the media from the adventitia is another elastic band known as the external elastic lamina.

Tunica adventitia of artery (histological slide)

The tunica adventitia is the thickest layer in the veins, and is entirely composed of connective tissue. However, in large and medium-sized vessels, the adventitia contains nerves and small arterioles (nutrient capillaries called the "vasa vasorum," literally, "vessels of the vessels") that supply that vessel and the outer half to two thirds of the media.

Additionally, arteries are divided into three types based on their size and structure:

  • Large elastic arteries (e.g., aorta, arch vessels, iliac and pulmonary arteries) - In this type, elastic fibers alternate with smooth muscle cells throughout the media, which expands during systole (storing some of the energy of each cardiac contraction), and recoils during diastole to propel blood distally. This elasticity is increasingly lost with age.
Ascending aorta (large elastic artery)
  • Medium-sized muscular arteries (e.g., coronary and renal arteries) - the media is composed primarily of smooth muscle cells, with elastin limited to the internal and external elastic lamina.
Left coronary artery (medium-sized muscular artery)
  • Small arteries (2 mm or less in diameter) and arterioles (20 to 100 μm in diameter) - The media in these vessels is mostly composed of smooth muscle cells.

Blood flow resistance is regulated at the arterioles and therefore pressure will drop during passage through the arterioles, causing blood flow to become more steady rather than pulsatile. This is due to the fact that under Poiseuille’s law, the resistance to fluid flow is inversely proportional to the fourth power of the diameter (i.e., halving the diameter increases resistance 16-fold), which means that small changes in arteriolar lumen size will have profound effects on blood pressure.


Liver is the organ where the VLDL molecules are produced

Inflammatory processes that set off a cascade of responses and changes over time initiate atherosclerosis. However, while a degree of atherosclerosis is found in a large majority of the population, its exact pathogenesis is still under debate. Typically, atherosclerosis begins in childhood with endothelial cells of the vessel wall, thought to be those associated with retained low-density lipoprotein (LDL) particles.

LDL particles are formed initially as VLDL lipoproteins. VLDL molecules are produced by the liver from triacylglycerol and cholesterol from the diet that was not used during the synthesis of bile acids.

These VLDL molecules then lose triglyceride through the action of lipoprotein lipase, thus making them smaller and denser, containing a higher proportion of cholesterol esters. Lowered protein/lipid ratios result in less dense lipoproteins. LDL particles function as the primary major cholesterol carriers in the blood, with each particle containing approximately 1,500 molecules of cholesterol ester.

It is thought that the retention of LDL particles, in conjunction with inflammation, is what results in endothelial cell dysfunction that instigates the process of atherosclerosis. LDL particles and their content are susceptible to oxidation by free radicals, and are more prone to oxidation once inside the blood vessel wall. As a result, endothelial cells respond to these inflammatory processes by attracting monocyte white blood cells from the blood into the arterial walls, therefore transforming them to macrophages.

Endothelial cells (histological slide)

Therefore following endothelial cell dysfunction, there is an accumulation of white blood cells, as mostly macrophages and LDL particles. Macrophages (and some T-lymphocytes) ingest oxidized LDL particles, which results in “foam cell” formation, otherwise described in histopathology as “lipid-laden macrophages”. Buildup of these lipid-laden macrophages appear grossly as a thin layer of yellowish-white “fatty streaks” within the inner layers of artery walls beginning during childhood, and continue expanding over time.

If the foam cells are unable to process the oxidized LDL particles and recruit high-density lipoprotein (HDL) particles to remove the fats and cholesterol, then foam cells will continue to expand and eventually rupture. Rupture of foam cells results in the release of oxidized materials and fats in the artery wall that causes yet another cycle of inflammatory responses that attract more white blood cells and further inflames the artery. Fatty streaks will therefore contain both active cells that produce inflammation in addition to dead cell remnants.

At this point, there is a migration of vascular smooth muscle cells (VSMCs) to these sites of inflammation, where endogenously released substances including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), endothelin-1, and IL-1 influence additional VSMC migration and proliferation. Recent research has shown that VSMCs respond to vascular injury by switching from the quiescent ‘contractile’ phenotype to a proinflammatory phenotype. Additionally, there will be deposition of extracellular matrix by VSMCs and further T-cell recruitment to these sites. Oftentimes, these remnants and accumulations will grow to eventually include calcium and other crystallized materials within the outermost and oldest plaque layers.

The fibrous plaque formed at this stage will become a complex atheroma with many layers of “hardening” material. The plaque will form a "fibrous cap" over the atheroma that is composed of bundles of VSMCs, macrophages, foam cells, lymphocytes, collagen and elastin of varying densities and ages, which makes the fibrous cap prone to rupture and ulceration that can lead to thrombosis.

Plaque rupture can include mechanical and/or biological risk factors. Mechanical factors can be shear stress or rupture of the vasa vasorum. Biological risks can include complex interactions between factors that regulate synthesis and degradation of extracellular matrix, such as platelet-derived growth factor (a potent stimulus for VSMC proliferation), or transforming growth factor-beta (a potent stimulus of collagen synthesis by VSMCs). Accumulation of T-lymphocytes and macrophages within the plaque could also decrease its stability due to inflammatory cytokines (e.g. interferon-gamma) and proteolytic enzymes (e.g. matrix metalloproteinases) that can be released, especially during vascular remodeling. Much of this activity occurs during physiologic stress that results in inflammation and vascular injury.

Multiple atheromatous plaques will be formed within the arteries and their presence will reduce the elasticity of the artery wall since SMCs of the blood vessel stretch to accommodate the growing plaque, and the endothelial lining of vessels will thicken, increasing the separation between the plaque and lumen. Blood flow will not be majorly affected since the muscular wall of the artery will enlarge at plaque locations to accommodate the changes happening slowly over time (this is also called arterial remodelling). Although, artery wall stiffening as a result of advanced disease may eventually cause a widened pulse pressure within major arteries.

As mentioned previously, the vessel walls of major, large elastic arteries, also known as Windkessel vessels (e.g. aorta, common carotid, subclavian, and pulmonary arteries and their larger branches), contain elastic fibers that allow these arteries to distend when the blood pressure rises during systole and recoil when the blood pressure falls during diastole.

The shape of this arterial blood pressure waveform is therefore described by the Windkessel effect, which accounts for the interaction between the stroke volume and the compliance of the Windkessel vessels. The Windkessel effect helps in damping the fluctuation in blood pressure (pulse pressure) over the cardiac cycle and helps maintain organ perfusion during diastole when cardiac ejection ceases. Due to artery wall stiffening, there will be a decreased Windkessel effect due to the loss of recoil of elastic arteries stemming from the loss of elastin.

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