Transitional changes in the structure of C-reactive protein create highly pro-inflammatory molecules: Therapeutic implications for cardiovascular diseases.

Mar 7, 2022

Contributor: J Zeller,B Bogner,J D McFadyen,J Kiefer,D Braig,G Pietersz,G Krippner,T L Nero,C J Morton,K S Cheung Tung Shing,M W Parker,K Peter,S U Eisenhardt

Transitional changes in the structure of C-reactive protein create highly pro-inflammatory molecules: Therapeutic implications for cardiovascular diseases.

C-reactive protein (CRP) is the prototypic acute-phase reactant that has long been recognized almost exclusively as a marker of inflammation and predictor of cardiovascular risk. However, accumulating evidence indicates that CRP is also a direct pathogenic pro-inflammatory mediator in atherosclerosis and cardiovascular diseases. The ‘CRP system’ consists of at least two protein conformations with distinct pathophysiological functions. The binding of the native, pentameric CRP (pCRP) to activated cell membranes leads to a conformational change resulting in two highly pro-inflammatory isoforms, pCRP* and monomeric CRP (mCRP). The deposition of these pro-inflammatory isoforms has been shown to aggravate the localized tissue injury in a broad range of pathological conditions including atherosclerosis and thrombosis, myocardial infarction, and stroke. Here, we review recent findings on how these structural changes contribute to the inflammatory response and discuss the transitional changes in the structure of CRP as a novel therapeutic target in cardiovascular diseases and overshooting inflammation.
Copyright © 2021. Published by Elsevier Inc.

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About The Expert

J Zeller

Department of Plastic and Hand Surgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany; Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. Electronic address: johannes.zeller@baker.edu.au.

B Bogner

Department of Plastic and Hand Surgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany.

J D McFadyen

Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Melbourne, Victoria, Australia.

J Kiefer

Department of Plastic and Hand Surgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany.

D Braig

Department of Plastic and Hand Surgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany; Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Munich, Germany.

G Pietersz

Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Cardiometabolic Health, The University of Melbourne, Parkville, Victoria, Australia.

G Krippner

Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

T L Nero

Department of Cardiometabolic Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia.

C J Morton

Department of Cardiometabolic Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia.

K S Cheung Tung Shing

Department of Cardiometabolic Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia.

M W Parker

Department of Cardiometabolic Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia; ACRF Rational Drug Discovery Centre, St. Vincent’s Institute of Medical Research, Fitzroy, Victoria, Australia.

K Peter

Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Melbourne, Victoria, Australia; Department of Cardiometabolic Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Immunology, Monash University, Melbourne, Victoria, Australia.

S U Eisenhardt

Department of Plastic and Hand Surgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany.

References

PubMed