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Pathophysiological Mechanisms of Carotid Plaque Vulnerability: Impact on Ischemic Stroke

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  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

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.

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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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Authors and Affiliations

  1. Clinic for Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Ismaninger Str. 22, 81675, Munich, Germany

    Jaroslav Pelisek, Hans-Henning Eckstein & Alma Zernecke

  2. Rudolf Virchow-Center/DFG-Research Center for Experimental Medicine, University of Würzburg, 97080, Würzburg, Germany

    Alma Zernecke

Authors
  1. Jaroslav Pelisek
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  2. Hans-Henning Eckstein
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  3. Alma Zernecke
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Correspondence to Jaroslav Pelisek.

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Pelisek, J., Eckstein, HH. & Zernecke, A. Pathophysiological Mechanisms of Carotid Plaque Vulnerability: Impact on Ischemic Stroke. Arch. Immunol. Ther. Exp. 60, 431–442 (2012). https://doi.org/10.1007/s00005-012-0192-z

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  • DOI: https://doi.org/10.1007/s00005-012-0192-z

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