Neointimal formation is reduced after arterial injury in human crp transgenic mice

Danenberg, Haim; Grad, Etty; Swaminathan, Rajesh V.; Chen, Zhiping; Seifert, Philip; Szalai, Alexander J.; Lotan, Chaim; Simon, Daniel I.; Edelman, Elazer R.

doi:10.1016/j.atherosclerosis.2008.01.013

Cited by 10 publications

(8 citation statements)

References 46 publications

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“…Given the potential benefits of transgenic approaches for investigating the biologic effects of increased levels of CRP, many investigators have used transgenic mice expressing human CRP to study its role in atherosclerosis and cardiovascular function14–19. However, relatively little work has been done in these models with respect to pathogenesis of features of the metabolic syndrome and risk factors for diabetes.…”

Section: Discussionmentioning

confidence: 99%

Effects of Human C-Reactive Protein on Pathogenesis of Features of the Metabolic Syndrome

et al. 2011

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Major controversy exists as to whether increased C-reactive protein (CRP) contributes to individual components of the metabolic syndrome or is just a secondary response to inflammatory disease processes. We measured blood pressure and metabolic phenotypes in spontaneously hypertensive rats (SHR) in which we transgenically expressed human CRP in liver under control of the apoE promoter. In SHR transgenic rats, serum levels of human CRP approximated the endogenous levels of CRP normally found in the rat. Systolic and diastolic blood pressures measured by telemetry were 10–15 mmHg greater in transgenic SHR expressing human CRP than in SHR controls (P<0.01). During oral glucose tolerance testing, transgenic SHR exhibited hyperinsulinemia compared to controls (insulin area under the curve 36±7 versus 8±2 nmol/L/2h, respectively, P<0.05). Transgenic SHR also exhibited resistance to insulin stimulated glycogenesis in skeletal muscle (174±18 versus 278±32 nmol glucose/g/2h, P<0.05), hypertriglyceridemia (0.84±0.05 versus 0.64±0.03 mmol/L, P<0.05), reduced serum adiponectin (2.4±0.3 versus 4.3±0.6 mmol/L, P<0.05), and microalbuminuria (200±35 versus 26±5 mg albumin/g creatinine, respectively, P<0.001). Transgenic SHR had evidence of inflammation and oxidative tissue damage with increased serum levels of interleukin 6 (IL6) (36.4±5.2 versus 18±1.7 pg/ml, P<0.005) and increased hepatic and renal TBARS (1.2±0.09 versus 0.8±0.07 and 1.5±0.1 versus 1.1±0.05 nM/mg protein, respectively, P<0.01), suggesting that oxidative stress may be mediating adverse effects of increased human CRP. These findings are consistent with the hypothesis that increased CRP is more than just a marker of inflammation and can directly promote multiple features of the metabolic syndrome.

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Section: Discussionmentioning

confidence: 99%

Effects of Human C-Reactive Protein on Pathogenesis of Features of the Metabolic Syndrome

et al. 2011

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“…94 Furthermore, there is evidence that the impact of FcγR and their ligands on neointima development may relate to their modulation of thrombosis, since in a trans-femoral artery wire injury model in which thrombosis was controlled with aspirin and heparin, CRP transgenic mice displayed less neointima formation. 95 The interpretation of findings regarding neointima development with FcγR manipulation may be complex because the FcγR γ chain plays a key role in platelet activation by collagen, and platelet activation may be instrumental to neointima initiation and progression. 96 Overall, the animal model data available to date indicate that FcγR impact thrombotic and non-thrombotic vascular occlusion.…”

Section: Fcγ Receptors Ligands and Cvd In Animal Modelsmentioning

confidence: 99%

Fcγ Receptors and Ligands and Cardiovascular Disease

Tanigaki

Sundgren

Khera

et al. 2015

Circulation Research

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Fcγ receptors (FcγR) classically modulate intracellular signaling upon binding of the Fc region of IgG in immune response cells. How FcγR and their ligands impact cardiovascular health and disease has recently been interrogated in both preclinical and clinical studies. The stimulation of activating FcγR in endothelial cells, vascular smooth muscle cells and monocytes/macrophages causes a variety of cellular responses that may contribute to vascular disease pathogenesis. Stimulation of the lone inhibitory FγcR, FcγRIIB, also has adverse consequences in endothelial cells, antagonizing NO production and reparative mechanisms. In preclinical disease models, activating FcγR promote atherosclerosis whereas FcγRIIB is protective, and activating FcγR also enhance thrombotic and non-thrombotic vascular occlusion. The FcγR ligand C-reactive protein (CRP) has undergone intense study. Although in rodents CRP does not impact atherosclerosis, it causes hypertension and insulin resistance and worsens myocardial infarction. Massive data has accumulated indicating an association between increases in circulating CRP and coronary heart disease in humans. However, Mendelian randomization studies reveal that CRP is not likely a disease mediator. CRP genetics and hypertension warrants further investigation. Studies to date of genetic variants of activating FcγR are insufficient to implicate the receptors in coronary heart disease pathogenesis in humans. However, a link between FcγRIIB and human hypertension may be emerging. Further knowledge of the vascular biology of FcγR and their ligands will potentially enhance our understanding of cardiovascular disorders, particularly in patients whose greater predisposition for disease is not explained by traditional risk factors, such as individuals with autoimmune disorders.

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“…Thus, those with chronic ischemia with elevated levels of CRP may have compromised eNO production and attenuated proliferation of EPC that may impedes healing process [22]. This is supported by the observation that mice with elevated levels of CRP showed a significantly faster and higher rate of arterial thrombosis [23]. Furthermore, volunteers receiving recombinant human CRP (rh-CRP) showed inappropriately activated coagulation system [24].…”

Section: Discussionmentioning

confidence: 99%

Serum C-reactive Protein As a Possible Marker to Predict Delayed Hemorrhage After Colonoscopic Polypectomy

Han

Fan

et al. 2012

Med Sci Monit

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SummaryBackgroundPost-polypectomy hemorrhage is one of the complications of colonscopic polypectomy. And there is no definitive and convenient laboratory test that could be used to predict risk of delayed post-polypectomy hemorrhage. This research aimed to study risk prediction of delayed post-polypectomy hemorrhage using serum C-reactive protein (CRP) level as a marker.Material/MethodsIn a retrospective, case-controlled study, 302 cases of post-polypectomy patients were divided into hemorrhage group and non-hemorrhage group. The CRP levels 24-hours after colonscopic treatment were compared between the two groups to assess whether elevated serum CRP levels in addition to other risk factors such as age, gender, smoking, alcohol consumption, hypertension (AHT) and size of polyps may predict risk of delayed post-polypectomy hemorrhage.ResultsThe hemorrhage group had significantly higher levels of serum CRP (32.50±17.34 mg/L vs. 6. 32±6.02 mg/dL) and were also having a higher incidence of hypertension compared to the non- hemorrhage group (both P<0.05). Patients with elevated serum CRP levels (≥10mg/L) after colonscopic treatment are at a higher risk of developing post-polypectomy hemorrhage (OR 1.329, 95%CI 1.125–1.571) as compared with patients whose CRP levels were not increased.ConclusionsA higher level of serum CRP may serve as an indicator of delayed post-polypectomy hemorrhage and there appears to be a direct relationship between the serum CRP levels and the risk of post-polypectomy hemorrhage: the higher CRP levels the higher the risk of post-polypectomy hemorrhage.

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Neointimal formation is reduced after arterial injury in human crp transgenic mice

Cited by 10 publications

References 46 publications

Effects of Human C-Reactive Protein on Pathogenesis of Features of the Metabolic Syndrome

Effects of Human C-Reactive Protein on Pathogenesis of Features of the Metabolic Syndrome

Fcγ Receptors and Ligands and Cardiovascular Disease

Serum C-reactive Protein As a Possible Marker to Predict Delayed Hemorrhage After Colonoscopic Polypectomy

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