Targeting C-reactive protein for the treatment of cardiovascular disease

  title={Targeting C-reactive protein for the treatment of cardiovascular disease},
  author={Mark B. Pepys and Gideon M. Hirschfield and Glenys A. Tennent and J. Ruth Gallimore and Melvyn C. Kahan and Vittorio Bellotti and Philip N. Hawkins and Rebecca M. Myers and Martin Derrick Smith and Alessandra Polara and Alexander J. A. Cobb and Steven V. Ley and John A. Aquilina and Carol V. Robinson and Isam Sharif and Gillian A. Gray and Caroline Anne Sabin and Michelle C. Jenvey and Simon E. Kolstoe and Darren A. Thompson and Steve P. Wood},
Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein… 
Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models
Evaluating the efficacy of CRP specific ASOs in rodents with experimentally induced cardiovascular damage might pave the way towards a placebo-controlled trial that could clarify the role ofCRP in cardiovascular disease.
C-reactive protein and coronary disease: is there a causal link?
Several recent findings have reduced the likelihood that CRP itself is a major causal mediator in CHD, and the strengths and limitations of the available data are summarized.
Human C-Reactive Protein Enhances Vulnerability of Immature Rats to Hypoxic-Ischemic Brain Damage: A Preliminary Study
Investigation of the hypothesis that C-reactive protein (CRP), which is not specific for infection, aggravates vulnerability of the immature brain to HI, suggests that human CRP-enhanced susceptibility to HI-induced brain damage is suggested.
The Role and Clinical Significance of High-Sensitivity C-Reactive Protein in Cardiovascular Disease
  • H. Seo
  • Medicine, Biology
    Korean circulation journal
  • 2012
Patients with high CRP concentrations are more likely to develop stroke, myocardial infarction, and significant peripheral vascular disease; a study showed that trans-fat consumption is related to high blood levels of CRP.
Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites
It is demonstrated that pCRP by binding to cell-derived microvesicles undergoes a structural change without disrupting the pentameric symmetry (pCRP*), which might improve the outcome of myocardial infarction, stroke and other inflammatory conditions.
Role of C-Reactive Protein at Sites of Inflammation and Infection
mounting evidence that CRP isoforms have distinct biological properties, with nCRP often exhibiting more anti-inflammatory activities compared to mCRP, and further studies are needed to expand on these emerging findings.
The effect of C-reactive protein deposition on myocardium with ischaemia-reperfusion injury in rats.
The results strongly suggest the active participation of the deposition of CRP on AAR in the progression of myocardial infarction following ischaemia-reperfusion injury, accompanied by complement activation and mitochondrial change.
Role of C-reactive protein in cerebrovascular disease: a critical review
A critical appraisal of the strengths and deficiencies of the accumulated evidence is required, both to consider the current state of knowledge and to inform the design of future research.


Human C-Reactive Protein Increases Cerebral Infarct Size after Middle Cerebral Artery Occlusion in Adult Rats
  • R. Gill, J. Kemp, C. Sabin, M. Pepys
  • Biology, Medicine
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2004
It is shown that adult rats subjected to middle cerebral artery occlusion and then treated with human CRP similarly developed significantly larger cerebral infarcts compared with control subjects receiving human serum albumin.
Transgenic human C-reactive protein is not proatherogenic in apolipoprotein E-deficient mice.
It is shown that transgenic expression of human CRP had no effect on development, progression, or severity of spontaneous atherosclerosis, or on morbidity or mortality, in male apolipoprotein E (apoE)-deficient C57BL/6 mice up to 56 weeks, despite deposition of humanCRP and mouse complement component 3 in the plaques.
Proinflammatory Effects of Bacterial Recombinant Human C-Reactive Protein Are Caused by Contamination With Bacterial Products, Not by C-Reactive Protein Itself
It is confirmed that this recombinant CRP preparation was proinflammatory both for mouse macrophages in vitro and for mice in vivo, but it is shown that pure natural human CRP had no such activity.
Complement and atherogenesis: binding of CRP to degraded, nonoxidized LDL enhances complement activation.
It is reported that addition of LDL and CRP to human serum did not result in significant C3 turnover, and results indicated that CRP binds to phosphorylcholine groups that become exposed in enzymatically degraded LDL particles.
Measurement of serum C-reactive protein concentration in myocardial ischaemia and infarction.
Increased CRP production is a non-specific response to tissue injury and raised CRP levels in cases of chest pain with a normal CK MB indicated a pathological process other than myocardial infarction.
Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis
A drug is developed that is a competitive inhibitor of SAP binding to amyloid fibrils and also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP.
Isolation and characterization of C-reactive protein and serum amyloid P component in the rat.
Rat CRP closely resembled human CRP in its amino acid composition, in having five subunits per molecule and in its electron microscopic appearance as a pentameric annular disc, but differed from murine SAP which is a major acute phase reactant.
Inducible nitric oxide synthase‐derived superoxide contributes to hypereactivity in small mesenteric arteries from a rat model of chronic heart failure
It is demonstrated that inducible nitric oxide synthase is expressed in mesenteric arteries from rats with chronic heart failure, however, instead of generating large quantities of NO, iNOS appears to be generating superoxide, perhaps because of a deficiency in its substrate, L‐arginine.
Localization and function of ET‐1 and ET receptors in small arteries post‐myocardial infarction: Upregulation of smooth muscle ETB receptors that modulate contraction
The endothelium is identified as the primary site of ET‐1 synthesis in small arteries and the ETA receptor as mediating the effects ofET‐1 in these vessels and ETB receptor expression increases in vascular smooth muscle post‐MI and is linked to mechanisms that inhibit the contractile response to ET‐ 1.