How are monocytes involved in atherosclerosis?

During the development and exacerbation of atherosclerosis, monocytes infiltrate the vessel wall and become lesional macrophages. Macrophages ingest oxidized lipoproteins via scavenger receptors and, as lipid-rich foam cells, contribute to the physical bulk of developing plaques.

How do foam cells form in atherosclerosis?

Foam cells are formed when circulating monocyte-derived cells are recruited to the atherosclerotic lesion site or fat deposits in the blood vessel walls.

How macrophage foam cells develop atherosclerosis?

Macrophage foam cells play a critical role in the occurrence and development of atherosclerosis. When inflow and esterification of cholesterol increase and/or its outflow decrease, the macrophages are ultimately transformed into lipid-laden foam cells, the prototypical cells in the atherosclerotic plaque.

Do foam cells initiate atherosclerosis?

Foam cells play a central role in the pathogenesis of atherosclerosis. Specifically, the formation and accumulation of foam cells in the subendothelial space of a damaged artery is one of the early key steps responsible for the development of atherosclerosis [14,15].

What cells are included in the mononuclear phagocytic system?

The mononuclear phagocyte system (MPS) has been defined as a family of cells comprising bone marrow progenitors, blood monocytes and tissue macrophages. Macrophages are a major cell population in most of the tissues in the body, and their numbers increase further in inflammation, wounding and malignancy.

What causes this to happen arteriosclerosis?

Atherosclerosis happens when the endothelium becomes damaged, due to factors such as smoking, high blood pressure, or high levels of glucose, fat, and cholesterol in the blood. This damage allows a collection of substances, known as plaque, to build up in the artery wall. These substances include fat and cholesterol.

Which step occurs first in the process of atherosclerosis?

The oxidation of low density lipoprotein (LDL) to Ox-LDL indicates the first step of atherosclerosis in cardiovascular diseases. Malondialdehyde factor shows the level of lipoperoxidation and is a sign of increased oxidative pressure and cardiovascular diseases.

What does a foam cell do?

Foam cells are a type of macrophage that localize to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance.

What is the role of macrophages in atherosclerosis?

Macrophages in atherosclerotic cardiovascular disease play a central role in the development of plaques. Classically activated M1 macrophages are implicated in initiating and sustaining inflammation, and alternatively activated or M2 macrophages are linked to inflammation resolution.

How does atherosclerosis develop?

Atherosclerosis thickening or hardening of the arteries. It is caused by a buildup of plaque in the inner lining of an artery. Plaque is made up of deposits of fatty substances, cholesterol, cellular waste products, calcium, and fibrin. As it builds up in the arteries, the artery walls become thickened and stiff.

What kind of muscle cells are involved in atherosclerosis?

1: Overview of the role of VSMCs in atherosclerosis. Vascular smooth muscle cells (VSMCs) are a major source of plaque cells and extracellular matrix (ECM) at all stages of atherosclerosis and contribute to numerous processes throughout the disease.

What is the pathophysiology of atherosclerosis?

Atherosclerosis is the pathologic process of lipid accumulation, scarring, and inflammation in the vascular wall, particularly the subendothelial (intimal) space of arteries, leading to vascular wall thickening, luminal stenosis, calcification, and in some cases thrombosis.

What causes monocytosis in hypercholesterolemic mice with atherosclerosis?

Interestingly, the monocytosis in hypercholesterolemic mice derives primarily from an increase in the more inflammatory LY6Chisubset, which makes up the majority of cells recruited to progressing atherosclerotic plaques and which is thought to be the source of the M1 (classically activated) macrophages found in the plaques 9–11.

What is the mechanism of foam cell formation?

The mechanisms of foam cell formation have been intensely studied (reviewed in 27 ). Although macrophages can clear APOB-containing lipoproteins through the low-density lipoprotein (LDL) receptor, expression of this receptor is downregulated early during foam cell formation by the increased cellular cholesterol levels.

What happens to macrophages in atherosclerotic plaques?

Notably, macrophages that accumulate in atherosclerotic plaques appear to have a diminished capacity to migrate, which contributes to failure to resolve inflammation and to progression of these lesions to more advanced, complex plaques in which other immune cell subsets and vascular smooth muscle cells participate in the inflammatory process2.

How much higher are monocytes in apolipoprotein E deficient mice?

In apolipoprotein E-deficient (Apoe−/−) mice, circulating monocytes are ∼50% higher than in wild-type mice9,10. How does hypercholesterolemia cause monocytosis?