Acute Phase Reactants as Novel Predictors of Cardiovascular Disease

Ahmed, M. S.; Jadhav, Ashok; Hassan, Alaa Ali; Meng, Qing H.

doi:10.5402/2012/953461

Cited by 81 publications

(79 citation statements)

References 234 publications

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“…One possibility for the effect of ribose-cysteine on Lp(a) is that the apo(a) transgene, which is under the control of a transferrin promoter, could be affected. Transferrin is a negative acute phase response protein regulated by inflammatory cytokines [43], the levels of which could be altered by the antioxidant effects of ribosecysteine. However, this possibility seems unlikely given that there was no significant change in apo(a) levels in the livers of ribosecysteine treated animals (Suppl.…”

Section: Discussionmentioning

confidence: 99%

Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice

et al. 2014

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“…This estimate yielded 5 major acute‐phase glycoproteins that were then shown to produce GlycA signals in proportion to their glycan N ‐acetyl glucosamine concentrations (J. Otvos, PhD, LipoScience Inc, personal communication, 2014). Their findings indicate that α1‐acid glycoprotein, haptoglobin, α1‐antitrypsin, α1‐antichymotrypsin, and transferrin—all of which have been implicated in the development of CVD—make major contributions to the GlycA signal. Biomarker profiling by NMR spectroscopy in an Estonian Biobank study found α1‐acid glycoprotein to be significantly predictive of cardiovascular mortality, a finding that was validated in a replication cohort .…”

Section: Discussionmentioning

confidence: 99%

A Novel Protein Glycan Biomarker and Future Cardiovascular Disease Events

Akinkuolie

Buring

Ridker

et al. 2014

JAHA

192

213

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BackgroundGlycosylated proteins partake in multiple cellular processes including inflammation. We hypothesized that GlycA, a novel biomarker of protein glycan N‐acetyl groups, is related to incident cardiovascular disease (CVD), and we compared it with high‐sensitivity C‐reactive protein (hsCRP).Methods and ResultsIn 27 491 initially healthy women, baseline GlycA was quantified by nuclear magnetic resonance spectroscopy and hsCRP by an immunoturbidimetric assay. During median follow‐up of 17.2 years, 1648 incident CVD events occurred (myocardial infarction, ischemic stroke, coronary revascularization, and CVD death). GlycA and hsCRP were moderately correlated (Spearman r=0.61, P<0.0001). In Cox regression models that included age, ethnicity, smoking, blood pressure, medications, menopausal status, body mass index, and diabetes, hazard ratios for CVD across quartiles 1 to 4 of GlycA were 1.00, 1.10 (95% CI, 0.92 to 1.30), 1.34 (95% CI, 1.13 to 1.58), and 1.64 (95% CI, 1.39 to 1.93), similar to hsCRP, for which hazard ratios were 1.00, 1.18 (95% CI, 0.99 to 1.41), 1.35 (95% CI, 1.14 to 1.61), and 1.75 (95% CI, 1.47 to 2.09) (both Ptrend<0.0001). Associations were attenuated after additionally adjusting for lipids: the hazard ratio of quartile 4 versus 1 for GlycA was 1.23 (95% CI, 1.04 to 1.46; Ptrend=0.002) and for hsCRP was 1.44 (95% CI, 1.20 to 1.72; Ptrend<0.0001). Further adjustment for the other biomarker resulted in a hazard ratio of quartile 4 versus 1 for GlycA of 1.03 (95% CI, 0.85 to 1.24; Ptrend=0.41) and for hsCRP of 1.29 (95% CI, 1.06 to 1.56; Ptrend=0.001).ConclusionsIn this prospective study of initially healthy women, baseline GlycA was associated with incident CVD, consistent with a possible role for protein glycans in inflammation and CVD.Clinical Trial RegistrationURL: http//clinicaltrials.gov/. Unique identifier NCT00000479.

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“…CREBH has been shown to directly activate the transcription of acute-phase genes encoding SAP and CRP upon exposure to the pro-inflammatory cytokines IL-1β and IL-6 [22]. Although apoB has not been classified as an APR gene, an early and consistent increase of plasma VLDL has been observed during APR [32, 33]. Our study demonstrated that the CREBH-apoB axis is the signaling pathway that, at least partially, mediated upregulation of VLDL in APR induced by TNFα and LPS.…”

Section: Resultsmentioning

confidence: 99%

CREBH mediates metabolic inflammation to hepatic VLDL overproduction and hyperlipoproteinemia

et al. 2017

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Metabolic inflammation is closely associated with hyperlipidemia and cardiovascular disease. However, the underlying mechanisms are not fully understood. The current study established that cAMP-responsive-element-binding protein H (CREBH), an acute-phase transcription factor, enhances very-low-density lipoprotein (VLDL) assembly and secretion by upregulating apolipoprotein B (apoB) expression, and contributes to metabolic inflammation-associated hyperlipoproteinemia induced by TNFα, lipopolysaccharides (LPS), and a high-fat diet (HFD) in mice. Specifically, overexpression of CREBH significantly induced mRNA and protein expression of apoB in McA-7777 cells. Luciferase assay further revealed that the presence of CREBH could significantly increase the activities of the apoB gene promoter. In contrast, genetic depletion of CREBH in mice resulted in significant reduction in expression of hepatic apoB mRNA. Challenging mice with an acute fat load led to upregulation of triglyceride (TG)-rich lipoprotein secretion in wildtype mice, but not in CREBH-null mice. TNFα treatment activated hepatic CREBH expression, which in turn enhanced hepatic apoB biosynthesis and VLDL secretion. Metabolic inflammation induced by LPS or HFD also resulted in overproduction of apoB and hyperlipoproteinemia in wildtype mice, but not in CREBH-null mice. This study demonstrates that CREBH could be a mediator between metabolic inflammation and hepatic VLDL overproduction in chronic metabolic disorders. This novel finding establishes CREBH as the first transcription factor that regulates apoB expression on the transcriptional level and the subsequent VLDL biosynthesis in response to metabolic inflammation. The study also provides novel insight into the pathogenesis of hyperlipidemia in metabolic syndrome.

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Acute Phase Reactants as Novel Predictors of Cardiovascular Disease

Cited by 81 publications

References 234 publications

Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice

Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice

A Novel Protein Glycan Biomarker and Future Cardiovascular Disease Events

CREBH mediates metabolic inflammation to hepatic VLDL overproduction and hyperlipoproteinemia

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