C-reactive protein: From innocent bystander to pivotal mediator of atherosclerosis

Labarrere, Carlos A.; Zaloga, Gary P.

doi:10.1016/j.amjmed.2004.03.039

Cited by 134 publications

(121 citation statements)

References 97 publications

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“…Thus, a number of molecules are currently available to assess endothelial function and the ongoing inflammatory process in the vascular wall. 28 Ageing produces a progressive decline in both large artery and small artery elasticity consistent with the well-recognized relationship between age and the risk for cardiovascular events. 29 In contrast, CRP did not increase with age and did not correlate with small artery elasticity, a marker for endothelial dysfunction, or with the biochemical markers for atherosclerosis risk.…”

Section: Discussionsupporting

confidence: 62%

Relationship between C-reactive protein and arterial stiffness in an asymptomatic population

et al. 2005

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Plasma concentration of high sensitive C-reactive protein (hsCRP) is used as a marker for inflammatory states and is directly correlated with the risk for coronary heart disease. Evidence concerning the role of inflammation in atheroma formation has been derived from several models of atherosclerosis. Inflammation should exert its adverse vascular effects by structural changes in the artery wall and consequently alterations in arterial elasticity, which could be detected already in asymptomatic early vascular disease. We hypothesized that CRP is related to large artery elasticity, but not to small artery elasticity in early vascular disease. Therefore, we examined the association between arterial stiffness of large and small arteries and inflammation in an asymptomatic population referred for primary prevention cardiovascular screening. Studies were performed in 391 subjects (age 21-82 years; 254 men, 137 women) who underwent screening at the Cardiovascular Disease Prevention Center. Large artery (C1) and small artery (C2) elasticity indices were obtained by the CVProfiler 2000 (HDI, Eagan, MN, USA). After overnight fasting, venous samples were taken for measurement of hsCRP, lipids, glucose. There was a significant inverse correlation between hsCRP (0.2970.40 mg/dl) and C1 (16.775.8 ml/mmHg), r ¼ À0.133, P ¼ 0.01; there was no significant correlation between hsCRP and C2 (6.673.2 ml/mmHg). C2, but not hsCRP, was inversely correlated with age, abnormal lipids and glucose, whereas C1, but not hsCRP, was inversely correlated with age and systolic blood pressure (SBP). In multiple regression analysis, the relationship between hsCRP and C1 was not affected by age, body mass index, SBP, serum glucose or lipids. In conclusion, these findings support the hypothesis that hsCRP, a marker for acute and low-grade inflammation, is associated with large artery but not with small artery elasticity in asymptomatic individuals undergoing primary prevention cardiovascular screening.

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Section: Discussionsupporting

confidence: 62%

Relationship between C-reactive protein and arterial stiffness in an asymptomatic population

et al. 2005

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“…CRP, a marker of acute inflammation and tissue damage, is an independent risk factor for cardiovascular and systemic diseases [8]. Besides its commonly accepted role of bystander in various inflammatory diseases, CRP also plays an active role in atherogenesis [9,10].…”

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confidence: 99%

Effects of C-reactive protein on human pulmonary vascular cells in chronic thromboembolic pulmonary hypertension

et al. 2012

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Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by proximal pulmonary vascular obstruction by thrombo-fibrotic material, the origin of which has not been elucidated. Enhanced inflammation could contribute to persistent obstruction by impairing pulmonary vascular cell function in CTEPH. We investigated C-reactive protein (CRP) effects on pulmonary vascular cell function in vitro.Primary cultures of proximal pulmonary endothelial cells (ECs) and smooth muscle cells (SMCs) from CTEPH and nonthromboembolic pulmonary hypertension (PH) patients were established. Recombinant CRP effects on mitogenic activity, adhesion capacity, endothelin-1 and von Willebrand factor (vWF) secretion and intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1 expression were investigated in ECs and/or SMCs. Expression of the CRP receptor, lectin-like oxidised low-density lipoprotein receptor (LOX)-1, was evaluated in proximal pulmonary arterial tissue and cells by Western blotting and immunofluorescence.CRP increased CTEPH-SMC proliferation by 250%. CRP increased adhesion capacity, endothelin-1 and vWF secretion by CTEPH-ECs by 37%, 129% and 694%, respectively. CRP-induced adhesion of CTEPH-ECs to monocytes was mediated by ICAM-1. CRP had no effect on cells from nonthromboembolic PH patients, probably because of overexpression of LOX-1 in CTEPH. Local expression of CRP was detected in ECs and SMCs within pulmonary arterial tissue.CRP may contribute to persistent obstruction of proximal pulmonary arteries in CTEPH by promoting vascular remodelling, endothelial dysfunction and in situ thrombosis. KEYWORDS: C-reactive protein, chronic thromboembolic pulmonary hypertension, endothelial cells, inflammation, smooth muscle cells C hronic thromboembolic pulmonary hypertension (CTEPH) is one of the main causes of severe pulmonary hypertension. CTEPH is characterised by intraluminal thrombus organisation and fibrous stenosis or complete obliteration of proximal pulmonary arteries. The consequence is an increased pulmonary vascular resistance resulting in pulmonary hypertension (PH) and progressive right heart failure. Pulmonary embolism, either as single or recurrent episodes, is thought to be the initiating event followed by progressive pulmonary vascular remodelling. CTEPH mainly differs from pulmonary arterial hypertension (PAH) by the proximal location of pulmonary artery obliteration [1].To date, the physiopathology of CTEPH remains poorly understood. Proximal lesions share similarities with atherosclerotic plaques, including media thickening and neointima formation [2]. Besides evidence of dysregulated thrombosis and/or thrombolysis, an elevated prevalence of inflammatory diseases has been observed in CTEPH patients [3]. Accordingly, plasma levels of tumour necrosis factor-a are elevated in CTEPH [4] and elevated pulmonary vascular resistance is correlated with increased expression of the CCL2 chemokine monocyte chemoattractant protein-1 in the plasma and large pulmonary arteries of CTE...

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“…CRP has been shown to exert proinflammatory and proatherogenic activities in many experiments using cultured vascular cells (39,40). The results obtained from cell culture experiments using purified CRP remain a subject of concern because of the presence of sodium azide and endotoxins in CRP and also because of the presence of modified forms of CRP, such as aggregated CRP, in preparations of native pentameric CRP (41)(42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein-Bound Enzymatically Modified Low-Density Lipoprotein Does Not Transform Macrophages into Foam Cells

Singh¹,

Suresh²,

Prayther³

et al. 2008

The Journal of Immunology

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The formation of low-density lipoprotein (LDL) cholesterol-loaded macrophage foam cells contributes to the development of atherosclerosis. C-reactive protein (CRP) binds to atherogenic forms of LDL, but the role of CRP in foam cell formation is unclear. In this study, we first explored the binding site on CRP for enzymatically modified LDL (E-LDL), a model of atherogenic LDL to which CRP binds. As reported previously, phosphocholine (PCh) inhibited CRP-E-LDL interaction, indicating the involvement of the PCh-binding site of CRP in binding to E-LDL. However, the amino acids Phe66 and Glu81 in CRP that participate in CRP-PCh interaction were not required for CRP-E-LDL interaction. Surprisingly, blocking of the PCh-binding site with phosphoethanolamine (PEt) dramatically increased the binding of CRP to E-LDL. The PEt-mediated enhancement in the binding of CRP to E-LDL was selective for E-LDL because PEt inhibited the binding of CRP to another PCh-binding site-ligand pneumococcal C-polysaccharide. Next, we investigated foam cell formation by CRP-bound E-LDL. We found that, unlike free E-LDL, CRP-bound E-LDL was inactive because it did not transform macrophages into foam cells. The function of CRP in eliminating the activity of E-LDL to form foam cells was not impaired by the presence of PEt. Combined data lead us to two conclusions. First, PEt is a useful compound because it potentiates the binding of CRP to E-LDL and, therefore, increases the efficiency of CRP to prevent transformation of macrophages into E-LDL-loaded foam cells. Second, the function of CRP to prevent formation of foam cells may influence the process of atherogenesis.

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C-reactive protein: From innocent bystander to pivotal mediator of atherosclerosis

Cited by 134 publications

References 97 publications

Relationship between C-reactive protein and arterial stiffness in an asymptomatic population

Relationship between C-reactive protein and arterial stiffness in an asymptomatic population

Effects of C-reactive protein on human pulmonary vascular cells in chronic thromboembolic pulmonary hypertension

C-Reactive Protein-Bound Enzymatically Modified Low-Density Lipoprotein Does Not Transform Macrophages into Foam Cells

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