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Keywords = pentameric form of C-reactive protein

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32 pages, 2228 KB  
Review
CRP Is a Key Indicator of Rheumatoid Arthritis-Associated Vascular Injury and Neurodegeneration
by Andreea Lazarut-Nistor, Melania Sibianu and Mark Slevin
Int. J. Mol. Sci. 2026, 27(11), 5001; https://doi.org/10.3390/ijms27115001 - 31 May 2026
Viewed by 737
Abstract
Systemic inflammation plays a pivotal role in the progression of rheumatoid arthritis (RA) and its associated comorbidities, ranging from cardiovascular (CV) disease to neurodegenerative conditions such as Alzheimer’s disease (AD). This narrative review examines the molecular cross-talk linking these pathologies, with a specific [...] Read more.
Systemic inflammation plays a pivotal role in the progression of rheumatoid arthritis (RA) and its associated comorbidities, ranging from cardiovascular (CV) disease to neurodegenerative conditions such as Alzheimer’s disease (AD). This narrative review examines the molecular cross-talk linking these pathologies, with a specific focus on the distinction between pentameric C-reactive protein (pCRP) and its proinflammatory monomeric form (mCRP). We discuss evidence suggesting that mCRP is not merely a passive marker but also an active driver of endothelial dysfunction, atherosclerosis, and synovial inflammation. This review further explores the connections among inflammatory biomarkers, blood vessel integrity, and neurodegeneration, detailing how persistent cytokine elevation (IL-6, TNF-α) and vascular injury contribute to cerebral small vessel disease (cSVD) and cognitive decline, with neurofilament light chain (NfL) serving as a key biomarker of neuroaxonal injury. Additionally, we address the neurobiology of pain in RA, highlighting the mechanisms of central sensitization (CS) and neuroimmune signalling that sustain pain-independent joint swelling. This evidence indicates that understanding the dynamic connection between CRP isoforms and neuronal markers should offer new insights for risk stratification and suggests that targeting mCRP may provide a novel therapeutic avenue to mitigate both articular and extra-articular manifestations of RA. Full article
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126 pages, 5707 KB  
Review
C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians
by Dimitra S. Mouliou
Diseases 2023, 11(4), 132; https://doi.org/10.3390/diseases11040132 - 28 Sep 2023
Cited by 154 | Viewed by 91714
Abstract
The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the [...] Read more.
The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the protein, along with further evidence on its potential pathobiology, both for its pentameric and monomeric forms, including information for its ligands as well as the possible function of autoantibodies against the protein. Furthermore, the current evidence on its potential utility as a biomarker of various diseases is presented, of all cardiovascular, respiratory, hepatobiliary, gastrointestinal, pancreatic, renal, gynecological, andrological, dental, oral, otorhinolaryngological, ophthalmological, dermatological, musculoskeletal, neurological, mental, splenic, thyroid conditions, as well as infections, autoimmune-supposed conditions and neoplasms, including other possible factors that have been linked with elevated concentrations of that protein. Moreover, data on molecular diagnostics on CRP are discussed, and possible etiologies of false test results are highlighted. Additionally, this review evaluates all current pieces of evidence on CRP and systemic inflammation, and highlights future goals. Finally, a novel diagnostic algorithm to carefully assess the CRP level for a precise diagnosis of a medical condition is illustrated. Full article
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20 pages, 1330 KB  
Review
Monomeric C-Reactive Protein in Atherosclerotic Cardiovascular Disease: Advances and Perspectives
by Ivan Melnikov, Sergey Kozlov, Olga Saburova, Yuliya Avtaeva, Konstantin Guria and Zufar Gabbasov
Int. J. Mol. Sci. 2023, 24(3), 2079; https://doi.org/10.3390/ijms24032079 - 20 Jan 2023
Cited by 47 | Viewed by 11195
Abstract
This review aimed to trace the inflammatory pathway from the NLRP3 inflammasome to monomeric C-reactive protein (mCRP) in atherosclerotic cardiovascular disease. CRP is the final product of the interleukin (IL)-1β/IL-6/CRP axis. Its monomeric form can be produced at sites of local inflammation through [...] Read more.
This review aimed to trace the inflammatory pathway from the NLRP3 inflammasome to monomeric C-reactive protein (mCRP) in atherosclerotic cardiovascular disease. CRP is the final product of the interleukin (IL)-1β/IL-6/CRP axis. Its monomeric form can be produced at sites of local inflammation through the dissociation of pentameric CRP and, to some extent, local synthesis. mCRP has a distinct proinflammatory profile. In vitro and animal-model studies have suggested a role for mCRP in: platelet activation, adhesion, and aggregation; endothelial activation; leukocyte recruitment and polarization; foam-cell formation; and neovascularization. mCRP has been shown to deposit in atherosclerotic plaques and damaged tissues. In recent years, the first published papers have reported the development and application of mCRP assays. Principally, these studies demonstrated the feasibility of measuring mCRP levels. With recent advances in detection techniques and the introduction of first assays, mCRP-level measurement should become more accessible and widely used. To date, anti-inflammatory therapy in atherosclerosis has targeted the NLRP3 inflammasome and upstream links of the IL-1β/IL-6/CRP axis. Large clinical trials have provided sufficient evidence to support this strategy. However, few compounds target CRP. Studies on these agents are limited to animal models or small clinical trials. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Cardiac Development and Disease)
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12 pages, 2948 KB  
Article
CRP Is Transported by Monocytes and Monocyte-Derived Exosomes in the Blood of Patients with Coronary Artery Disease
by Ivan Melnikov, Sergey Kozlov, Olga Saburova, Ekaterina Zubkova, Olga Guseva, Sergey Domogatsky, Tatiana Arefieva, Natalia Radyukhina, Maria Zvereva, Yuliya Avtaeva, Lyudmila Buryachkovskaya and Zufar Gabbasov
Biomedicines 2020, 8(10), 435; https://doi.org/10.3390/biomedicines8100435 - 19 Oct 2020
Cited by 21 | Viewed by 4187
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease)
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18 pages, 1376 KB  
Review
The Multiple Faces of C-Reactive Protein—Physiological and Pathophysiological Implications in Cardiovascular Disease
by Magdalena Boncler, Yi Wu and Cezary Watala
Molecules 2019, 24(11), 2062; https://doi.org/10.3390/molecules24112062 - 30 May 2019
Cited by 95 | Viewed by 12617
Abstract
C-reactive protein (CRP) is an intriguing protein which plays a variety of roles in either physiological or pathophysiological states. For years it has been regarded merely as a useful biomarker of infection, tissue injury and inflammation, and it was only in the early [...] Read more.
C-reactive protein (CRP) is an intriguing protein which plays a variety of roles in either physiological or pathophysiological states. For years it has been regarded merely as a useful biomarker of infection, tissue injury and inflammation, and it was only in the early 80s that the modified isoforms (mCRP) of native CRP (nCRP) appeared. It soon became clear that the roles of native CRP should be clearly discriminated from those of the modified form and so the impacts of both isoforms were divided to a certain degree between physiological and pathophysiological states. For decades, CRP has been regarded only as a hallmark of inflammation; however, it has since been recognised as a significant predictor of future episodes of cardiovascular disease, independent of other risk factors. The existence of modified CRP isoforms and their possible relevance to various pathophysiological conditions, suggested over thirty years ago, has prompted the search for structural and functional dissimilarities between the pentameric nCRP and monomeric mCRP isoforms. New attempts to identify the possible relevance between the diversity of structures and their opposing functions have initiated a new era of research on C-reactive protein. This review discusses the biochemical aspects of CRP physiology, emphasizing the supposed relevance between the structural biology of CRP isoforms and their differentiated physiological and pathophysiological roles. Full article
(This article belongs to the Section Medicinal Chemistry)
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