Abstract
C-reactive protein (CRP) is a widely recognized indicator of inflammation and is known to play an important role in atherogenesis. Recent prospective studies have demonstrated that increased CRP concentrations within the reference interval are a strong predictor of myocardial infarction, stroke, sudden cardiac death, and peripheral vascular disease in apparently healthy adults. The correlation of circulating CRP concentrations with the severity, extent, and progression of many different pathologies, and the prognostic significance of these associations, are consistent with CRP not just being a marker of disease but also contributing to pathogenesis. Knowledge of the structure and function of CRP — including its three-dimensional structure alone and complexed with ligands coupled with experience in developing an inhibitor of the related protein SAP (Amyloid P component, Serum) establishes an excellent platform for drug design
Highlights
Systemic inflammation is associated with leukocyte-mediated endothelial dysfunction[1]
Proinflammatory cytokines, chemokines, and glucocorticoid hormones are elaborated and stimulate hepatocytes to synthesize a wide array of acute phase proteins[2,3].A dominant acute phase protein in mammals, C-reactive protein (CRP) is a 206–amino acid pentameric polypeptide[4].Originally isolated from the serum of patients with pneumonia, it has a high binding affinity for pneumococcal C polysaccharide[5]
It has been speculated that CRP may have significant proinflammatory effects, and that, by binding to ligands exposed on cells or other autologous structures as a result of infection, inflammation, ischemia, and other pathologies, and triggering complement activation, it may exacerbate tissue damage, leading to more severe disease 41
Summary
Systemic inflammation is associated with leukocyte-mediated endothelial dysfunction[1]. 2. Structure CRP belongs to a family of pentameric proteins known as pentraxins. The structure of CRP contains a crystal contact where the calcium-binding loop from one protomer coordinates into the calcium site of a second protomer to form the pentameric structure. This configuration allows for the binding of the ligand phosphocholine and provides information concerning conformational changes related to calcium binding. Obesity, smoking, diabetes mellitus, lack of exercise, pregnancy and hormonal therapy (estrogens or progesterones) are associated with a mildly elevated CRP concentration[15]. Conditions or disease states where C reactive protein is elevated16 5.1 Acute inflammation: Bacterial infection, Pneumococcal pneumonia, Acute rheumatic fever, Bacterial endocarditis and Staphylococcal osteomyelitis 5.2 Chronic inflammation: Systemic lupus erythematosis, Rheumatic arthritis, Reiter’s syndrome, psoriatic arthriopathy, arthritis following jejuno-ileal bypass, Polyarteritis nodosa, disseminated,systemic vasculitis, cutaneous vasculitis, Polymyalgia rheumatic, Crohn’s disease, Ulcerative colitis, Dermomyositis, Osteoarthritis, Neoplastic diseases, Smokers, Obesity and Diabetes. 5.3 Tissue injury: Tissue injury and surgery and acute myocardial ischemia
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