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Dissociation of Pentameric to Monomeric C-Reactive Protein on Activated Platelets Localizes Inflammation to Atherosclerotic Plaques

Dissociation of Pentameric to Monomeric C-Reactive Protein on Activated Platelets Localizes... Molecular Medicine Dissociation of Pentameric to Monomeric C-Reactive Protein on Activated Platelets Localizes Inflammation to Atherosclerotic Plaques Steffen U. Eisenhardt, Jonathon Habersberger, Andrew Murphy, Yung-Chih Chen, Kevin J. Woollard, Nicole Bassler, Hongwei Qian, Constantin von zur Muhlen, Christoph E. Hagemeyer, Ingo Ahrens, Jaye Chin-Dusting, Alex Bobik, Karlheinz Peter Abstract—C-reactive protein (CRP) is a predictor of cardiovascular risk. It circulates as a pentamer (pentameric CRP) in plasma. The in vivo existence of monomeric (m)CRP has been postulated, but its function and source are not clear. We show that mCRP is deposited in human aortic and carotid atherosclerotic plaques but not in healthy vessels. pCRP is found neither in healthy nor in diseased vessels. As source of mCRP, we identify a mechanism of dissociation of pCRP to mCRP. We report that activated platelets, which play a central role in cardiovascular events, mediate this dissociation via lysophosphatidylcholine, which is present on activated but not resting platelets. Furthermore, the dissociation of pCRP to mCRP can also be mediated by apoptotic monocytic THP-1 and Jurkat T cells. The functional consequence is the unmasking of proinflammatory effects of CRP as demonstrated in experimental settings that are pathophysio- logically relevant for atherogenesis: compared to pCRP, mCRP http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Circulation Research Wolters Kluwer Health

Dissociation of Pentameric to Monomeric C-Reactive Protein on Activated Platelets Localizes Inflammation to Atherosclerotic Plaques

Peter, Karlheinz
Circulation Research , Volume 105 (2) – Jul 1, 2009
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ISSN
0009-7330
eISSN
1524-4571
DOI
10.1161/CIRCRESAHA.108.190611
pmid
19520972
Publisher site
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Abstract

Molecular Medicine Dissociation of Pentameric to Monomeric C-Reactive Protein on Activated Platelets Localizes Inflammation to Atherosclerotic Plaques Steffen U. Eisenhardt, Jonathon Habersberger, Andrew Murphy, Yung-Chih Chen, Kevin J. Woollard, Nicole Bassler, Hongwei Qian, Constantin von zur Muhlen, Christoph E. Hagemeyer, Ingo Ahrens, Jaye Chin-Dusting, Alex Bobik, Karlheinz Peter Abstract—C-reactive protein (CRP) is a predictor of cardiovascular risk. It circulates as a pentamer (pentameric CRP) in plasma. The in vivo existence of monomeric (m)CRP has been postulated, but its function and source are not clear. We show that mCRP is deposited in human aortic and carotid atherosclerotic plaques but not in healthy vessels. pCRP is found neither in healthy nor in diseased vessels. As source of mCRP, we identify a mechanism of dissociation of pCRP to mCRP. We report that activated platelets, which play a central role in cardiovascular events, mediate this dissociation via lysophosphatidylcholine, which is present on activated but not resting platelets. Furthermore, the dissociation of pCRP to mCRP can also be mediated by apoptotic monocytic THP-1 and Jurkat T cells. The functional consequence is the unmasking of proinflammatory effects of CRP as demonstrated in experimental settings that are pathophysio- logically relevant for atherogenesis: compared to pCRP, mCRP

Journal

Circulation Research – Wolters Kluwer Health

Published: Jul 1, 2009

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