Early verification of myocardial ischemia with a novel biomarker of acute tissue damage: C-reactive protein fractional forms

Kiefer, Charles R.; Stock, Rachel; Flanagan, Sharon S.; Darling, Chad E.; Smith, Craig S.; Snyder, Lois

doi:10.1016/j.cca.2012.06.023

Cited by 5 publications

(4 citation statements)

References 15 publications

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“…Moreover, many epidemiological studies have shown an association between CRP and cardiovascular risk [ 119 ], and its clinical utility is currently a topic of great debate, with novel proposals for scenarios where its evaluation may be useful, including the use of fractions of CRP as a new element in the diagnostic workup of patients with acute coronary syndrome [ 120 ] and the designation of CRP as a potential therapeutic target given its exhaustive involvement in the pathophysiology of atherosclerosis [ 121 ]. In this context, the results from the JUPITER study offer some insight into this possibility, by ascertaining better health outcomes in patients with lower CRP levels [ 122 ].…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein: An In-Depth Look into Structure, Function, and Regulation

Salazar

Martínez

Chávez-Castillo

et al. 2014

International Scholarly Research Notices

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Cardiovascular disease is the leading cause of morbidity and mortality in the adult population worldwide, with atherosclerosis being its key pathophysiologic component. Atherosclerosis possesses a fundamental chronic inflammatory aspect, and the involvement of numerous inflammatory molecules has been studied in this scenario, particularly C-reactive protein (CRP). CRP is a plasma protein with strong phylogenetic conservation and high resistance to proteolysis, predominantly synthesized in the liver in response to proinflammatory cytokines, especially IL-6, IL-1β, and TNF. CRP may intervene in atherosclerosis by directly activating the complement system and inducing apoptosis, vascular cell activation, monocyte recruitment, lipid accumulation, and thrombosis, among other actions. Moreover, CRP can dissociate in peripheral tissue—including atheromatous plaques—from its native pentameric form into a monomeric form, which may also be synthesized de novo in extrahepatic sites. Each form exhibits distinct affinities for ligands and receptors, and exerts different effects in the progression of atherosclerosis. In view of epidemiologic evidence associating high CRP levels with cardiovascular risk—reflecting the biologic impact it bears on atherosclerosis—measurement of serum levels of high-sensitivity CRP has been proposed as a tool for assessment of cardiovascular risk.

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Section: Discussionmentioning

confidence: 99%

C-Reactive Protein: An In-Depth Look into Structure, Function, and Regulation

Salazar

Martínez

Chávez-Castillo

et al. 2014

International Scholarly Research Notices

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“…Free mCRP has not been detected in the circulation (likely because of its relative aqueous insolubility), but mCRP has been found in atherosclerosis plaques [2], within infarctions [17], and detected bound to MPs in the circulation of patients following myocardial infarction (MI) [3]. mCRP presence on MPs has been reported to be due to dissociation of pCRP in the lipid environment of the membrane, specifically that the altered lysophospholipids therein overcome electrostatic forces holding together the monomeric units so that they dissociate [18]. Similar to apoptotic and activated cells, MPs contain phospholipids on their surface not typically exposed in the outer leaflet of cell membranes, including lysophosphatidylcholine (LPC).…”

Section: Introductionmentioning

confidence: 99%

Plasma Levels of Endothelial Microparticles Bearing Monomeric C-reactive Protein are Increased in Peripheral Artery Disease

Crawford

Trial

Nambi

et al. 2016

J. of Cardiovasc. Trans. Res.

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C-reactive Protein (CRP) as an indicator of cardiovascular disease (CVD) has shown limited sensitivity. We demonstrate that two isoforms of CRP (pentameric, pCRP and monomeric, mCRP) present in soluble form or on microparticles (MPs) have different biological effects and are not all measured by clinical CRP assays. The hsCRP assay did not measure pCRP or mCRP on MPs, whereas flow cytometry did. MPs derived from endothelial cells, particularly those bearing mCRP, were elevated in PAD patients compared to controls. The numbers of mCRP+ endothelial MPs did not correlate with hsCRP measurements of soluble pCRP, indicating their independent modulation. In controls, statins lowered mCRP+ endothelial MPs. In a model of vascular inflammation, mCRP induced endothelial shedding of MPs and was proinflammatory, while pCRP was anti-inflammatory. mCRP on endothelial MPs may be both an unmeasured indicator of, and an amplifier of, vascular disease, and its detection might improve risk sensitivity.

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“…The increase in mCRP concentration was also detected in patients with elevated pCRP concentration in plasma, unrelated to ischemic myocardial damage [ 20 ]. Another study reported a positive correlation between the rise in mCRP levels and troponin I in AMI [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

CRP Is Transported by Monocytes and Monocyte-Derived Exosomes in the Blood of Patients with Coronary Artery Disease

et al. 2020

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The objective of this work was to study the ability of blood cells and their microparticles to transport monomeric and pentameric forms of C-reactive protein (mCRP and pCRP) in the blood of patients with coronary artery disease (CAD). Blood was obtained from 14 patients with CAD 46 ± 13 years old and 8 healthy volunteers 49 ± 13.6 years old. Blood cells and microparticles with mCRP and pCRP on their surface were detected by flow cytometry. Messenger RNA (mRNA) of CRP was extracted from peripheral blood monocytes stimulated with lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF). mRNA of CRP in monocytes was detected with PCR. Monocytes were predominantly pCRP-positive (92.9 ± 6.8%). mCRP was present on 22.0 ± 9.6% of monocyte-derived exosomes. mCRP-positive leukocyte-derived microparticle counts were significantly higher (8764 ± 2876/µL) in the blood of patients with CAD than in healthy volunteers (1472 ± 307/µL). LPS and GM-CSF stimulated monocytes expressed CRP mRNA transcripts levels (0.79 ± 0.73-fold), slightly lower relative to unstimulated hepatocytes of the HepG2 cell line (1.0 ± 0.6-fold), but still detectable. The ability of monocytes to transport pCRP in blood flow, and monocyte-derived exosomes to transmit mCRP, may contribute to the maintenance of chronic inflammation in CAD.

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Early verification of myocardial ischemia with a novel biomarker of acute tissue damage: C-reactive protein fractional forms

Cited by 5 publications

References 15 publications

C-Reactive Protein: An In-Depth Look into Structure, Function, and Regulation

C-Reactive Protein: An In-Depth Look into Structure, Function, and Regulation

Plasma Levels of Endothelial Microparticles Bearing Monomeric C-reactive Protein are Increased in Peripheral Artery Disease

CRP Is Transported by Monocytes and Monocyte-Derived Exosomes in the Blood of Patients with Coronary Artery Disease

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