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Atherosclerosis

 

Atherosclerosis is the buildup of plaque on the inside walls of arteries. Plaque is made up of low density lipoprotein (LDL), macrophages, smooth muscle cells, platelets, and other substances. It may narrow the lumen of a blood vessel and restrict blood flow. Plaque rupture can induce the formation of thrombus (blood clot) and block blood flow. This will result in ischemic stroke or heart attack.

Formation of foam cells

The first stage in the development of atherosclerosis is the formation of foam cells (macrophages with ingested oxidized LDL). The process begins with trap of LDL in the intima, which lies just below the endothelium (the monolayer of cells lining the arterial wall). Trapped LDL could be oxidized, triggering recruitment of monocytes into the intima. Several adhesion molecules are involved, including vascular-cell adhesion molecule (VCAM), integrin, selectin, and others. After entering the intima, monocytes differentiate into macrophages and ingest oxidized LDL.

Formation of plaque

As atherosclerosis progresses, T lymphocytes, platelets and smooth muscle cells also join foam cells, expanding the plaque size. This involves cytokines to activate T lymphocytes and growth factors to promote proliferation of smooth muscle cells. Platelets can also release cytokines and growth factors to enhance migration and proliferation of smooth muscle cells. During this stage, a fibrous cap is formed to separate the plaque from the lumen.

Thrombosis

Thrombosis (formation of thrombus) arises from plaque rupture. Macrophages may release metalloproteinases and other proteolytic enzymes to degrade fibrous cap, making it susceptible to rupture. Plaque rupture activates platelets, leading to formation of  blood clots at the site of lesion (mechanism from Internet Stroke Center).

 

How to say NO to atherosclerosis
Molecular mechanisms for the production of nitric oxide (NO) by exercise leading to the protection of atherosclerosis.

 

Associated genes

APOA1
Encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL). Since HDL is less likely than LDL to enter the intima, high level of HDL is generally good for your health.

APOB
Encodes apolipoprotein B, which is the major protein component of LDL.

APOC2
Encodes a protein component of very low density lipoprotein (VLDL).

ABCA1
Encodes an ATP-binding cassette (ABC) transporter, which is involved in clearing excess cholesterol and generating HDL.

CCL2
Encodes the cytokine MCP-1 that has chemotactic activity for monocytes.

CETP
Encodes cholestery ester transfer protein. A deficiency of CETP is associated with increased HDL levels and decreased LDL levels (review).

CX3CR1
Encodes a chemokine receptor involved in cell adhesion (reference).

MMP9
Encodes a matrix metalloproteinase, which is involved in plaque rupture (review, polymorphism).

OLR1
Encodes oxidized LDL receptor.

 

Free Online Textbook:

Inflammatory Atherosclerosis - Richard Frink, 2002.

 

Review articles:

HDL/LDL

Blood

Immune System

Oxidative Stress

Miscellaneous