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Archivum Immunologiae et Therapiae Experimentalis

, Volume 60, Issue 6, pp 431–442 | Cite as

Pathophysiological Mechanisms of Carotid Plaque Vulnerability: Impact on Ischemic Stroke

  • Jaroslav Pelisek
  • Hans-Henning Eckstein
  • Alma Zernecke
Review

Abstract

Stroke is among the major causes of mortality and disabilities in the world. About 80 % of all strokes in the anterior circulation are ischemic and up to 20 % of all ischemic strokes are caused by extracranial atherosclerotic carotid artery stenosis. The prevalence of a cervical internal carotid artery stenosis increases with age and can be found in 6.9 % of the elderly population (>65 years). Atherosclerotic changes of the carotid vessel wall can lead to plaque vulnerability and may result in arterio-arterial embolism, which frequently underlie carotid-related cerebrovascular ischemic events. Carotid atherosclerosis is characterised by inflammation, extensive degradation of extracellular matrix components, neovascularization, and as recently recognised is also affected by epigenetic changes. These factors accelerate the progression of atherosclerosis towards vulnerable plaques and increase the risk of ischemic stroke. In this review, the main pathophysiological mechanisms leading to rupture-prone carotid artery plaques and successive ischemic stroke are considered. It is important to recognise the heterogeneity of atherosclerosis and that various pathophysiological processes dissected in this review are not acting individually, but rather in a complementary manner. The identification and careful integration of all relevant factors will be required for the development of future diagnostic and therapeutic strategies.

Keywords

Carotid atherosclerosis Vulnerable carotid plaque Ischemic stroke 

Abbreviations

ADAM

A disintegrin and metalloprotease domain

ADAMTS

ADAM-related metalloproteases with a thrombospondin domain

AGEs

Advanced glycation end products

Ang-1, -2

Angiopoietins-1 and -2

CEA

Carotid endarterectomy

CKD

Chronic kidney disease

DM

Diabetes mellitus

ECM

Extracellular matrix

Eph

Ephrins

FGF

Fibroblast growth factor

ICA

Internal carotid artery

HDL

High density lipoproteins

HIF-1

Hypoxia-inducible growth factor

IL

Interleukin

INF-γ

Interferon-gamma

LDL

Low density lipoproteins

oxLDL

Oxidised low density lipoproteins

LDL(-)

Electronegatively charged low density lipoproteins

MP

Metalloprotease

MMP

Matrix metalloprotease

PDGF

Platelet-derived growth factor

PGs

Proteoglycans

RAGE

AGE receptor

TNF-α

Tumour necrosis factor-alpha

VSMCs

Vascular smooth muscle cells

VEGF

Vascular endothelial growth factor

VEGFR

Vascular endothelial growth factor receptor

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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2012

Authors and Affiliations

  • Jaroslav Pelisek
    • 1
  • Hans-Henning Eckstein
    • 1
  • Alma Zernecke
    • 1
    • 2
  1. 1.Clinic for Vascular and Endovascular SurgeryKlinikum rechts der Isar der Technischen Universitaet MuenchenMunichGermany
  2. 2.Rudolf Virchow-Center/DFG-Research Center for Experimental MedicineUniversity of WürzburgWürzburgGermany

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