Monocytes and Macrophages in Atherosclerosis

Atherogenesis: hyperhomocysteinemia interactions with LDL, macrophage function, paraoxonase 1, and exercise

“…The significance of monocyte adhesion and uptake of lipoproteins is seen when there is an almost complete absence of atherosclerosis after M‐CSF or P‐selectin (a platelet‐ and endothelial‐related macrophage adhesion molecule) knockouts are introduced into murine models of dyslipidemia . Additionally, mice deficient in LDL receptors with marked reduction in VCAM‐1 exhibited less plaque formation than controls, which is also the case when the VCAM‐1 interaction is blocked with integrins in the ApoE knockout model …”

“…Macrophages have recently been parsed into at least two broad subtypes––M1 and M2––each of which plays specific roles in atherosclerosis The M1 macrophages are known as classically activated macrophages and are associated with inflammation, cell killing, and bacterial infections. The M2 macrophages are known as alternatively activated macrophages and include three different subtypes: (1) the M2a subtype is profibrotic and counters parasitic infections, (2) the M2b subtype is involved in immunity regulation, and (3) the M2c subtype promotes the anti‐inflammatory response and tissue repair and remodeling . There are specific factors or cytokines that cause the polarization of a macrophage to become M1 or M2.…”

“…The factors IL‐4 and IL‐10, secreted by T H 2 cells, cause a shift toward M2, while factors such as IFN‐γ are responsible for M1 polarization . M1 macrophages express high levels of CD40, CD80, IL‐6, IL‐12, TNF‐α, iNOS, and lower expression of IL‐10; while M2 macrophages express higher levels of CD163, CD206, arginase‐1, IL‐1β, and IL‐10 . Induction of the M2 phenotype depends on elevation of scavenger receptors CD36 and SR‐A1, which cause ER stress enhancement .…”

“…31,[106][107][108] Additionally, mice deficient in LDL receptors with marked reduction in VCAM-1 exhibited less plaque formation than controls, which is also the case when the VCAM-1 interaction is blocked with integrins in the ApoE knockout model. [109][110][111] Macrophages have recently been parsed into at least two broad subtypes--M1 and M2-each of which plays specific roles in atherosclerosis 4,38,59,112,113 The M1 macrophages are known as classically activated macrophages and are associated with inflammation, cell killing, and bacterial infections. The M2 macrophages are known as alternatively activated macrophages and include three different subtypes: (1) the M2a subtype is profibrotic and counters parasitic infections, (2) the M2b subtype is involved in immunity regulation, and (3) the M2c subtype promotes the anti-inflammatory response and tissue repair and remodeling.…”

“…The M2 macrophages are known as alternatively activated macrophages and include three different subtypes: (1) the M2a subtype is profibrotic and counters parasitic infections, (2) the M2b subtype is involved in immunity regulation, and (3) the M2c subtype promotes the anti-inflammatory response and tissue repair and remodeling. 59,110 There are specific factors or cytokines that cause the polarization of a macrophage to become M1 or M2. The factors IL-4 and IL-10, secreted by T H 2 cells, cause a shift toward M2, 61,114 while factors such as IFN-␥ are responsible for M1 polarization.…”