Persistent Activation of Nuclear Factor Kappa-B Signaling Pathway in Patients With Unstable Angina and Elevated Levels of C-Reactive Protein

Liuzzo, Giovanna; Santamaria, Matteo; Biasucci, Luigi M.; Narducci, Michela; Colafrancesco, Valeria; Porto, Annalisa; Brugaletta, Salvatore; Pinnelli, Michela; Rizzello, Vittoria; Maseri, Attilio; Crea, Filippo

doi:10.1016/j.jacc.2006.07.071

Cited by 71 publications

(13 citation statements)

References 49 publications

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“…Hs-CRP was examined because it is a well-documented inflammatory marker of future health problems including cardiovascular disease, diabetes, and cancer [10–12]. In fact, CRP appears to play a role in the inflammation that is a part of the atherogenic process [13, 14]. In this regard, prior work has linked positivity or negativity in relationships to inflammation [15, 16].…”

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confidence: 99%

The Strength of Family Ties: Perceptions of Network Relationship Quality and Levels of C-Reactive Proteins in the North Texas Heart Study

et al. 2015

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Background Although the quality of one’s social relationships has been linked to important physical health outcomes, less work has been conducted examining family and friends that differ in their underlying positivity and negativity. Purpose The main aim of this study was to examine the association between supportive, aversive, and ambivalent family/friends with levels of C-reactive proteins. Methods Three hundred participants from the North Texas Heart Study completed the social relationships index and a blood draw to assess high-sensitivity C-reactive proteins (hs-CRPs). Results After standard controls, the number of supportive family members predicted lower hs-CRP levels, whereas the number of ambivalent family members predicted higher hs-CRP levels. These links were independent of depressive symptoms and perceived stress. Conclusions These data highlight the importance of considering specific types of relationships and their underlying positive and negative aspects in research on social ties and physical health.

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confidence: 99%

The Strength of Family Ties: Perceptions of Network Relationship Quality and Levels of C-Reactive Proteins in the North Texas Heart Study

et al. 2015

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“…22,23 Patients with unstable coronary syndromes have evidence of NFκB activation in circulating blood monocytes that is associated with a higher risk of future cardiovascular events. 24,25 Thus, inhibition of NFκB-mediated inflammatory responses has been proposed as a strategy to ameliorate risk in coronary artery disease. 25,26 …”

Section: Discussionmentioning

confidence: 99%

“…24,25 Thus, inhibition of NFκB-mediated inflammatory responses has been proposed as a strategy to ameliorate risk in coronary artery disease. 25,26 …”

Section: Discussionmentioning

confidence: 99%

Effect of sulfasalazine on inflammation and endothelial function in patients with established coronary artery disease

et al. 2012

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Inflammation is critical for atherosclerosis development and may be a target for risk-reduction therapy. In experimental studies, activation of the inflammatory regulator, nuclear factor kappa B (NFlB), contributes to endothelial activation and reduced nitric oxide production. We treated patients with coronary artery disease with sulfasalazine, an inhibitor of NFκB, and placebo in a randomized, double-blind, crossover study design. Brachial artery flow-mediated dilation (FMD) and digital vascular function were measured at baseline and after each 6-week treatment period. Of the 53 patients enrolled in the crossover study, 32 (age 60 ± 10, 22% female) completed all the visits, with a high rate of study withdrawal due to gastrointestinal side effects. In a subset of 10 participants, we compared the effects of 4 days of sulfasalazine treatment (n = 5) to no treatment (n = 5) on NFκB-regulated gene expression in peripheral blood mononuclear cells. Tumor necrosis factor α-stimulated expression of CD69 and NFlB subunit p50 was significantly blunted after 4 days of sulfasalazine treatment but not after no treatment. However, FMD and digital vasodilator response did not significantly change from baseline with long-term sulfasalazine treatment. Short-term sulfasalazine inhibited NFlB activity; however, long-term treatment was poorly tolerated and did not improve endothelial function. Our findings suggest that sulfasalazine therapy is not the optimal anti-inflammatory treatment for reversing endothelial dysfunction in cardiovascular disease. Further studies are warranted to investigate the potential for NFlB inhibition to reduce cardiovascular risk.

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“…A recent study demonstrated that CRP may activate nuclear factor-B in human monocytes (38 ) and may be hypothesized as a new mechanism for CRP in regulating the generation of inflammatory mediators. However, CRP did not influence TF expression in the present study, suggesting that the proinflammatory phenotype of monocytes could not be directly modulated by CRP.…”

Section: Discussionmentioning

confidence: 99%

Tissue Factor and Monocyte Chemoattractant Protein-1 Expression in Hypertensive Individuals with Normal or Increased Carotid Intima-Media Wall Thickness

Sardo¹,

Campo²,

Mandraffino³

et al. 2008

Clinical Chemistry

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Background: People with hypertension display an inflammatory pattern that includes increased plasma concentrations of monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and enhanced expression of tissue factor (TF) mRNA in blood monocytes. Methods: In this study, we investigated the relationship between CRP concentrations and TF and MCP-1 mRNA expression in unstimulated and lipopolysaccharide (LPS)-stimulated monocytes isolated from hypertensives with or without an increase in carotid intima-media thickness (IMT). We also investigated the expression of TF and MCP-1 mRNA and MCP-1 protein after in vitro addition of CRP to monocytes. We measured CRP (by immunonephelometry) and monocyte expression of TF and MCP-1 (by real-time PCR) in 80 untreated hypertensive patients without clinical cardiovascular disease (CVD) or additional risk factors for CVD compared with 41 controls. Based on IMT measured by carotid Doppler ultrasonography, patients were classified into the categories of normal (≤1 mm) or abnormal (>1 mm). TF and MCP-1 mRNA and MCP-1 protein (by Western blotting) were measured after in vitro addition of CRP to monocytes from 10 randomized controls as well as 10 hypertensives with IMT ≤1 mm and 10 with IMT >1 mm. Results: CRP and TF and MCP-1 mRNA concentrations were significantly higher in IMT >1 mm hypertensives vs those with IMT ≤1 mm and controls. CRP had no effect on monocyte TF mRNA from either hypertensives or controls. CRP-stimulated monocytes from hypertensives, however, showed increased MCP-1 mRNA and protein expression compared with controls and LPS-stimulated cells. Conclusions: Our findings suggest that the inflammatory response of blood monocytes plays an important role in the development of atherosclerosis and hypertension.

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Persistent Activation of Nuclear Factor Kappa-B Signaling Pathway in Patients With Unstable Angina and Elevated Levels of C-Reactive Protein

Abstract: Nuclear factor kappa-B activation might represent a mechanism by which CRP amplifies and perpetuates the inflammatory component of acute coronary syndromes and influences the clinical outcome.

Cited by 71 publications

References 49 publications

The Strength of Family Ties: Perceptions of Network Relationship Quality and Levels of C-Reactive Proteins in the North Texas Heart Study

The Strength of Family Ties: Perceptions of Network Relationship Quality and Levels of C-Reactive Proteins in the North Texas Heart Study

Effect of sulfasalazine on inflammation and endothelial function in patients with established coronary artery disease

Tissue Factor and Monocyte Chemoattractant Protein-1 Expression in Hypertensive Individuals with Normal or Increased Carotid Intima-Media Wall Thickness

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