Are endothelial cells involved in atherosclerosis?

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Review article
Angiogenesis in the atherosclerotic plaque

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Open access

Highlights

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Intimal neovascularization in plaque growth and destabilization.

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Role of classical and specific angiogenic factors in atherosclerotic angiogenesis.

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Inflammation and oxidative stress promote angiogenesis and plaque destabilization.

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Angiogenesis promote intraplaque hemorrhages, afflux of blood cells and lipids.

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Anti-angiogenic therapy for atherosclerotic angiogenesis.

Abstract

Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.

Abbreviations

ADMA

assymetric methylarginine

ABCG1

ATP-binding cassette sub-family G member 1

AIBP

ApoA-I binding protein

ApoE−/− mice

homozygous ApoE-deficient mice

ARNT

aryl hydrocarbon nuclear translocator

CPT1A

carnitine palmityl transferase

EGF

epidermal growth factor

eNOS

endothelial nitric oxide synthase

ERK

extracellular signal-regulated kinase

FGF

basic fibroblast growth factor;

HDL

high density lipopoprotein

HIF

Hypoxia inducible factor

HSP

heparan sulfate proteoglycans

Flt-1

fms-like tyrosine kinase-1

HUVEC

human umbilical vein endothelial cell

ICAM-1

InterCellular Adhesion Molecule-1

iNOS

inducible nitric oxide synthase

LDLs

low density lipoproteins

MAPK

mitogen activated protein kinase

MMP

matrix metalloproteinase

NADPH

H+, nicotinamide adenine dinucleotide phosphate

nNOS

neuronal nitric oxide synthase

NF-kB

nuclear factor kappaB

PAI-1

plasminogen activator inhibitor 1

nSMase2

neutral sphingomyelinase-2

PDGF

platelet-derived growth factor

PI3K

phosphoinositide 3 kinase

PUFA

polyunsaturated fatty acid

PPAR

peroxisome proliferator activated receptor

RCT

reverse cholesterol transport

ROCK

Rho associated protein kinase

RTKs

receptor tyrosine kinase

ROS

reactive oxygen species

S1P

sphingosine 1-phosphate

Spns2

S1P carry spinster homolog 2

SRC

Sarcoma tyrosine kinase

TGF-β

transforming growth factor-β

TIMPs

Tissue Inhibitor of Metalloproteinases

VCAM-1

Vascular Cell Adhesion Molecule-1

VEGF

vascular endothelial growth factor

Keywords

Neovascularization

Angiogenesis

VEGF

Atherosclerosis

Hypercholesterolemia

Cited by [0]

What cells are involved in atherosclerosis?

Atherosclerosis is a multiphase process which is characterized with the activation of endothelial cells with the expression of adhesion molecules and monocytes/macrophages, and the transmigration of DCs, T cells and some B-cells into the intima, and also the transfer of modulated types of LDL to matrix components.

What happens to endothelial cells in atherosclerosis?

Endothelial cells [ECs] line all blood vessels and are critical mediators of inflammatory responses. In the setting of atherosclerosis, ECs become chronically activated through a combination of turbulent blood flow, lipid accumulation in the vessel wall and exposure to inflammatory mediators [for example, IL-1β]1.

What are endothelial cells responsible for?

Endothelial cells form a single cell layer that lines all blood vessels and regulates exchanges between the bloodstream and the surrounding tissues. Signals from endothelial cells organize the growth and development of connective tissue cells that form the surrounding layers of the blood-vessel wall.

What happens to cells during atherosclerosis?

Abstract— During the development of an atherosclerotic plaque, mononuclear leukocytes infiltrate the artery wall through vascular endothelial cells [ECs]. At the same time, arterial smooth muscle cells [SMCs] change from the physiological contractile phenotype to the secretory phenotype and migrate into the plaque.

Review articleAngiogenesis in the atherosclerotic plaque