Highlights
- •Subendothelial LDL-adhesion is a key event in the atherosclerotic lesion formation.
- •During oxidation aldehydes could leak out of the LDL-particle and modify nearby matrix proteins.
- •Aldehyde-collagen type IV correlated with oxidized LDL and was increased in symptomatic lesions.
- •Aldehyde-modification of collagen type IV decreased endothelial cell attachment.
- •Aldehyde-modification of collagen type IV may cause endothelial dysfunction and increase the risk of clinical events.
Abstract
Objective
Subendothelial LDL-adhesion and its subsequent oxidation are considered as key events
in the development of atherosclerotic lesions. During oxidation of LDL, reactive aldehydes
such as malondialdehyde (MDA) are formed, which modify apolipoprotein B100. However,
the possibility that these reactive aldehydes could leak out of the LDL-particle and
modify surrounding extracellular matrix proteins has been largely unexplored. We have
investigated if aldehyde-modification of collagen type IV, one of the major basement
membrane components, in plaques is associated with cardiovascular events.
Methods
The amount of MDA-modified collagen type IV and native collagen type IV were determined
in homogenates from 155 carotid artery lesions, removed by endarterectomy from patients
with or without previous cerebrovascular events.
Results
Plaque MDA-collagen type IV, but not native collagen type IV, correlated with oxidized
LDL (r = 0.31, P < 0.001) and lipoprotein-associated phospholipase A2 (r = 0.44, P < 0.001). MDA-collagen type IV was increased in lesions from symptomatic patients
compared to lesions from asymptomatic patients. Auto-antibodies against MDA-collagen
type IV in plasma correlated with the amount of MDA-collagen type IV in lesions. MDA-modification
of collagen type IV decreased endothelial cell attachment. In addition, culture of
endothelial cells with MDA-modified collagen type IV increased vascular cell adhesion
molecule expression and reduced the anti-coagulant proteins thrombomodulin and endothelial
protein C receptor. In the lesions native collagen type IV, but not MDA-collagen type
IV, was positively associated with thrombomodulin.
Conclusion
The present observations imply that aldehyde-modification of collagen type IV, associated
with LDL oxidation, in atherosclerotic plaques may cause endothelial dysfunction and
increase the risk of clinical events.
Keywords
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Article info
Publication history
Published online: February 24, 2015
Accepted:
February 22,
2015
Received in revised form:
February 13,
2015
Received:
October 29,
2014
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
