Serum Biomarkers of Atherosclerosis

Ox-LDL

Initiation and progression of atherosclerosis by inducing dysfunction in endothelial cells (ECs)

An excess of oxygen and nitrogen free radicals modify lipids, proteins, and carbohydrates within the intima, the innermost lining of the artery, altering their behavior and function.

Oxidized LDL, in particular, plays a nefarious role in promoting atherosclerosis. It induces endothelial dysfunction, triggers an inflammatory immune response, and activates macrophages. These macrophages then take up oxidized LDL, become foam cells, and create the fatty streaks that characterize atherosclerotic plaque.

This plaque can become unstable and rupture, triggering coagulation, forming blood clots and thrombi, and eventually blocking the artery.

High-density lipoprotein may protect against CVD by removing lipids from the endothelium and impeding the production of foam cells.

sdLDLs

Provide oxidized cholesterol for developing atherosclerotic plaque

Have an extended circulation time, are prone to oxidation, and easily penetrate the intima.

Significantly increase atherosclerosis risk, and their elevation is considered a risk factor for cardiovascular disease.

Associated with phenotype B, metabolic disorders, including obesity and type 2 diabetes, coronary heart disease, and hypertriglyceridemia.

Lp(a)

Pro-inflammatory action on the arterial wall due to oxidized phospholipids and atherogenic and pro-thrombotic activity associated with the homology with plasminogen

Consists of a lipoprotein molecule bound to apolipoprotein B, the protein portion of LDL.

Is proinflammatory, prothrombotic, and carries atherogenic oxidized phospholipids.

CRP

Non-specific indicator of inflammation upregulated due to vascular disease.

Independently predicts primary and secondary coronary heart disease events

Upregulates cell adhesion molecules, enhances release of MCP-1, facilitates the uptake of LDL into macrophages

Triggered by various mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF).

Binds the cell membrane of activated monocytes but not resting monocytes.

Induces the polarization of monocytes towards the M1 phenotype and converts M2 monocytes into the M1 phenotype, thereby promoting the recruitment of monocytes into the plaque.

Is found within atherosclerotic plaque and damaged vessel walls, where it plays a role in its secretion

Can be produced outside the liver, including by cell types within atherosclerotic plaque which may result in concentrations several times higher within atherosclerotic plaques compared with serum levels.

CRP receptors have been identified in various other cell types, such as neutrophils, resident macrophages, and endothelial cells.

High-sensitivity CRP testing can detect low levels of CRP that may be associated with chronic low-level inflammation.

M1-like macrophages

Induce the recruitment and activation of other macrophages, T cells, B cells, and dendritic cells, promoting inflammation and advancing atherosclerotic plaque development.

The accumulation of intravascular lipids recruits monocytes to atherosclerosis-prone areas, where they differentiate into macrophages.

Subsequently, these macrophages undergo metabolic reprogramming in response to atherogenic stimuli present in the plaque microenvironment, such as modified lipoproteins and hypoxia.

M2-like macrophages

Secrete anti-inflammatory and pro-fibrotic mediators and help limit inflammation, thus inhibiting the progression of atherosclerosis.

M2-like macrophages secrete anti-inflammatory and pro-fibrotic mediators and help limit inflammation, thus inhibiting the progression of atherosclerosis.

Early regression of atherosclerosis can occur through increased apoptosis of cholesterol-laden macrophages, followed by the uptake of these apoptotic cells by neighboring macrophages.