BACKGROUND & AIMS:Recently, novel inborn errors of metabolism were identified because of mutations in V-ATPase assembly factors TMEM199 and CCDC115. Patients are characterized by generalized protein glycosylation defects, hypercholesterolemia, and fatty liver disease. Here, we set out to characterize the lipid and fatty liver phenotype in human plasma, cell models, and a mouse model.METHODS AND RESULTS:Patients with TMEM199 and CCDC115 mutations displayed hyperlipidemia, characterized by increased levels of lipoproteins in the very low density lipoprotein range. HepG2 hepatoma cells, in which the expression of TMEM199 and CCDC115 was silenced, and induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells from patients with TMEM199 mutations showed markedly increased secretion of apolipoprotein B (apoB) compared with controls. A mouse model for TMEM199 deficiency with a CRISPR/Cas9-mediated knock-in of the human A7E mutation had marked hepatic steatosis on chow diet. Plasma N-glycans were hypogalactosylated, consistent with the patient phenotype, but no clear plasma lipid abnormalities were observed in the mouse model. In the siTMEM199 and siCCDC115 HepG2 hepatocyte models, increased numbers and size of lipid droplets were observed, including abnormally large lipid droplets, which colocalized with lysosomes. Excessive de novo lipogenesis, failing oxidative capacity, and elevated lipid uptake were not observed. Further investigation of lysosomal function revealed impaired acidification combined with impaired autophagic capacity.CONCLUSIONS:Our data suggest that the hypercholesterolemia in TMEM199 and CCDC115 deficiency is due to increased secretion of apoB-containing particles. This may in turn be secondary to the hepatic steatosis observed in these patients as well as in the mouse model. Mechanistically, we observed impaired lysosomal function characterized by reduced acidification, autophagy, and increased lysosomal lipid accumulation. These findings could explain the hepatic steatosis seen in patients and highlight the importance of lipophagy in fatty liver disease. Because this pathway remains understudied and its regulation is largely untargeted, further exploration of this pathway may offer novel strategies for therapeutic interventions to reduce lipotoxicity in fatty liver disease.

To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17–516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman’s rho, 0.42; P < 10 −5 ) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease.

Objective Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota–immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT). Design Patients with recent-onset (<6 weeks) T1D (18–30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition. Results Stimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=−0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics. Conclusion FMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D. Trial registration number NTR3697.

OBJECTIVE:Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS.DESIGN:In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring.RESULTS:A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated.CONCLUSIONS:A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.TRIAL REGISTRATION NUMBER:NTR-NL6630.

Dysbiosis of the intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We performed a phase I/II dose-finding and safety study on the effect of oral intake of the anaerobic butyrogenic strain Anaerobutyricum soehngenii on glucose metabolism in 24 subjects with metabolic syndrome. We found that treatment with A. soehngenii was safe and observed a significant correlation between the measured fecal abundance of administered A. soehngenii and improvement in peripheral insulin sensitivity after 4 weeks of treatment. This was accompanied by an altered microbiota composition and a change in bile acid metabolism. Finally, we show that metabolic response upon administration of A. soehngenii (defined as improved insulin sensitivity 4 weeks after A. soehngenii intake) is dependent on microbiota composition at baseline. These data in humans are promising, but additional studies are needed to reproduce our findings and to investigate long-term effects, as well as other modes of delivery.

The American Board of Emergency Medicine (ABEM) gathers extensive background information on emergency medicine–sponsored residency and fellowship programs, residents and fellows training in those programs, and all fellows for whom ABEM issues subspecialty certifications. We present the 2019 annual report on the status of US emergency medicine training programs.

Introduction and Methods: Elevated circulating levels of Triglyceride-rich Remnant Lipoproteins (TLR) are strongly associated with increased risk for CVD. The hepatic clearance of TRL involves lipoprotein receptors i.e. the low-density lipoprotein receptor (LDLr) and heparin sulfate proteoglycans (HSPG). The relevance of each pathway in humans remains to be established. To further dissect the relative contribution of each of these receptors, we studied postprandial TRL metabolism with an oral fat tolerance test using cream supplemented with retinyl palmitate (RP) in 1) patients with a heterozygous loss-of-function (LOF) variant in LDLR stratified for a low (n=10) or high (n=10) HSPG gene score; 2) patients with heterozygous LOF variants in EXT1 or EXT2 (n=13), characterised by decreased HSPG chains length but normal sulfation pattern, and compared to matched healthy controls (n=13) and 3) diabetic patients (n=29) stratified for a functional SNP in SULF2, that predisposes to lower SULF2 expression and increased 6-O-sulfation of HSPG chains. Results: Postprandial TRL clearance was significantly delayed in patients with FH compared to controls (AUC-RP FH: 1971±190 vs Con: 646±110 nmol/l/h;P<0.0001 and iAUC-TG FH 6.9±1.0 vs Con 3.8±10 mmol/l/h, P<0.05) supporting the important role of LDLr in TRL clearance. No additional effect was observed if the FH group was stratified for HSPG gene score. Also, in patients with LOF variants in EXT, resulting in shorter HSPG chains, no difference in TRL clearance versus controls could be observed. In contrast, improved 6-O-sulfation due to lower hepatic protein expression of SULF2 resulted in improved fasting and postprandial TG levels and significantly lower iAUC-RP (iAUC-TG AA 6.9±1.1 vs GG 4.1±1.2 mmol/l/h P<0.05; AUC-RP AA 97±15 vs GG 15±2 mg/l/h; P<0.001) Conclusion: Our findings clearly indicate an important role for the LDLr in postprandial TRL clearance in humans. In contrast to murine studies, HSPGs do only modestly contribute to hepatic TRL clearance in humans, and implicate that sulfation of HSPG’s is of more relevance for TRL clearance than HSPG chain length.

Objective An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid profile are limited. Therefore, changes in lipids in RTX treated RA patients were evaluated. Methods In 49 consecutive RTX treated RA patients, serum and EDTA plasma samples were collected at baseline, 1, 3 and 6 months. In these samples, lipid and levels were assessed to determine changes in time. Surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) MS analysis was performed in six good and six non-responding RA patients to study functional high density lipoprotein (HDL) protein composition changes in time. Results In the total group (n=49), the atherogenic index decreased from 4.3 to 3.9 (∼9%) after 6 months. Testing for effect modification revealed a difference in the effect on lipid levels between responders and non-responders upon RTX (p<0.001). ApoB to ApoA-I ratios decreased significantly (∼9%) in good responding (n=32) patients. SELDI-TOF MS analysis revealed a significant decrease in density of mass charge (m/z) marker 11743, representing a decrease in serum amyloid A, in good responding patients. Conclusion This study indicates beneficial effects on cholesterol profile upon RTX treatment along with improvement of disease activity. Proteomic analysis of the HDL particle reveals composition changes from proatherogenic to a less proatherogenic composition during 6 months RTX treatment. Whether these HDL particle alterations during immunotherapies result in a lower CV event rate remains to be established.

A chronic inflammatory state is a risk factor for accelerated atherogenesis. The aim of our study was to explore whether Crohn's disease (CD), characterized by recurrent inflammatory episodes, is also associated with accelerated atherogenesis. In 60 CD patients and 122 matched controls, carotid intima media thickness (IMT), a validated marker for the burden and progression of atherosclerosis, was assessed ultrasonographically. Additional subgroup analyses, including plasma levels of acute phase reactants and HDL protein profiling, were performed in 11 consecutive patients with CD in remission, 10 patients with active CD, and 15 healthy controls. Carotid IMT in patients with CD was increased compared with healthy volunteers: 0.71 (0.17) versus 0.59 (0.14) mm (P < 0.0001), respectively. In the subgroup analysis, HDL levels in controls and patients in remission were identical [(1.45 (0.48) and 1.40 (0.46) mmol/l; P = 0.797], whereas HDL during exacerbation was profoundly reduced: 1.02 (0.33) (P = 0.022). HDL from patients with active CD and CD patients in remission was characterized by a reduced ability to attenuate oxidation compared with controls (P = 0.008 and P = 0.024 respectively). Patients with CD have increased IMT compared with matched controls, indicative of accelerated atherogenesis. The changes during CD exacerbation in terms of HDL concentration and composition imply a role for impaired HDL protection in these patients.

Introduction: Atherosclerosis has been characterized as a low-grade chronic inflammatory disease. Conversely, accelerated atherogenesis has been shown to be a hallmark of chronic inflammatory disea...

HomeCirculation ResearchVol. 97, No. 12 Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUB Radjesh Bisoendial, Rakesh Birjmohun, Tymen Keller, Sander van Leuven, Han Levels, Marcel Levi, John Kastelein and Erik Stroes Radjesh BisoendialRadjesh Bisoendial Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands Search for more papers by this author , Rakesh BirjmohunRakesh Birjmohun Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands Search for more papers by this author , Tymen KellerTymen Keller Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands Search for more papers by this author , Sander van LeuvenSander van Leuven Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands Search for more papers by this author , Han LevelsHan Levels Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands Search for more papers by this author , Marcel LeviMarcel Levi Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands Search for more papers by this author , John KasteleinJohn Kastelein Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands Search for more papers by this author and Erik StroesErik Stroes Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands Search for more papers by this author Originally published9 Dec 2005https://doi.org/10.1161/01.RES.0000196746.75724.8bCirculation Research. 2005;97:e115–e116To the Editor:We have diligently read the research commentary by Pepys et al,1 which among others addresses the in vivo effects of C-reactive protein (CRP)- infusion into humans, as recently reported by us in a previous issue of this journal.2 We would like to clarify some misconceptions surrounding our study, as generated in their report. Pepys et al observed, using recombinant human (rh)CRP that still contained large quantities of endotoxin, that this rhCRP solution induced an inflammatory reaction both in vitro as well as in mice, whereas CRP from human resources had no such effect. Pepys et al then extrapolate these findings to our study in humans and conclude that the in vivo effects of rhCRP we observed must have been caused by contaminants rather than rhCRP itself. In fact, these authors arrive at the wrong conclusion, and they fail to acknowledge several shortcomings in their own experiments.First, their dialysed commercial rhCRP displayed residual endotoxin activity of 46·6 endotoxin units (EU) per mg of rhCRP and would for that sake never have been allowed for human use. In comparison, endotoxin activity of our rhCRP was 30× lower (<1·5 EU/mL), which resulted in less than 1·6 EU per mg of rhCRP (at a CRP concentration of 0·91 mg/mL). Interestingly, the trace amounts in our rhCRP are very similar to those reported by Pepys et al in their natural human (nh)CRP solution, ie, 0·9 EU/mg of nhCRP. Needless to state that extrapolation of their findings, using highly contaminated rhCRP, to our study results does not make any sense.Second, Pepys et al argued that contaminants, rather than CRP, are responsible for the inflammatory effects in humans and tested this hypothesis in a mouse model. Using rhCRP with very high endotoxin activity, they observe a substantial acute phase response in accord with previous reports on the clinical sequelae of endotoxin.3 Nevertheless, Pepys et al fail to acknowledge that the residual endotoxin levels in our rhCRP have been proven insufficient to cause any bioactivity in vivo4 and in vitro. Notably, data on nhCRP now provided by Pepys et al, containing comparable amounts of endotoxin as our rhCRP, further corroborate this observation. To even further substantiate this, we infused lipopolysaccharide (LPS; E coli lipopolysaccharide, lot G2B274, United States Pharmacopeial Convention Inc, Rockville, Md) into two healthy volunteers at a dose (1·5 EU/kg) that equaled the mean coinfused dose during the CRP infusion experiments. Compared with the reference values of higher dose LPS infusion (10 EU/kg; n=4) and rhCRP infusion (n=4) groups, none of the subjects receiving the low dose LPS infusion showed any change in TNF-α, as assayed by cytometric bead array analysis (BD Biosciences; Figure). Despite the heterogeneity in potency among endotoxins of different sources, these data demonstrate that the trace amounts of endotoxin present in our rhCRP-solution cannot have contributed to the inflammatory reactions we observed in our human study subjects. Download figureDownload PowerPointEffects of intravenous injection of 1·5 EU/kg LPS, 10 EU/kg LPS, and 1·25 mg/kg rhCRP on temperature, hematological responses, and systemic inflammation in humans. Mean±SE values of temperature, leukocyte numbers, percentage monocytes, and levels of TNF-α are depicted. Compared with reference values of high-dose LPS (n=4) and rhCRP (n=4) groups, none of the subjects of the low-dose LPS group (n=2) developed an increase in body temperature. No early leukopenia with monocyte depletion was observed. Further, antigen levels of TNF-α remained unaltered during the experiments.Third, it should be noted that assessing CRP biology in a mouse model has been criticized. As emphasized by Reifenberg et al, the mouse is not a suitable model for assessment of the consequences of human CRP on atherogenesis.5 The latter is most markedly illustrated by the complete absence in this rodent model of one of the main biological functions of CRP, ie, lipoprotein-dependent complement activation. In line, recent observations in genetically engineered mice that regard the effect of human CRP on atherosclerosis are rather contradictory.6,7Finally, the statement by Pepys et al that the massive SAA response to rhCRP infusion may even increase risk of AA amyloidosis is completely misplaced. In reality, the SAA levels observed in our study are comparable to SAA levels seen in adults infected with uncomplicated influenza.8In conclusion, we concur with Pepys et al that data on the downstream proinflammatory consequences of CRP must be interpreted with caution. However, the data currently generated by Pepys et al bear no relevance with respect to our findings in humans. This is attributable, among others, to the 30-fold higher endotoxin activity in their solution as well as to the use of a rodent model in evaluating the effects of human CRP. Hence, we still whole-heartedly support Pepys in his conclusion that CRP represents an attractive target for cardiovascular prevention.1 Pepys MB, Hawkins PN, Kahan MC, Tennant GA, Gallimore JR, Graham D, Sabin CA, Zychlinsky A, Diego J de. Pro-inflammatory effects of bacterial recombinant human C-reactive protein are caused by contamination with bacterial products not by C-reactive protein itself. Circ Res. 2005; 97: e97–e103.CrossrefMedlineGoogle Scholar2 Bisoendial RJ, Kastelein JJ, Levels JH, Zwaginga JJ, van den BB, Reitsma PH, Meijers JC, Hartman D, Levi M, Stroes ES. Activation of inflammation and coagulation after infusion of C-reactive protein in humans. Circ Res. 2005; 96: 714–716.CrossrefMedlineGoogle Scholar3 Haudek SB, Natmessnig BE, Redl H, Schlag G, Hatlen LE, Tobias PS. Isolation, partial characterization, and concentration in experimental sepsis of baboon lipopolysaccharide-binding protein. J Lab Clin Med. 2000; 136: 363–370.CrossrefMedlineGoogle Scholar4 Levi M, Ten Cate H, Bauer KA, van der PT, Edgington TS, Buller HR, Van Deventer SJ, Hack CE, ten Cate JW, Rosenberg RD. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest. 1994; 93: 114–120.CrossrefMedlineGoogle Scholar5 Reifenberg K, Lehr HA, Baskal D, Wiese E, Schaefer SC, Black S, Samols D, Torzewski M, Lackner KJ, Husmann M, Blettner M, Bhakdi S. Role of C-reactive protein in atherogenesis:can the apolipoprotein E knockout mouse provide the answer? Arterioscler Thromb Vasc Biol. 2005; 25: 1641–1646.LinkGoogle Scholar6 Paul A, Ko KW, Li L, Yechoor V, McCrory MA, Szalai AJ, Chan L. C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2004; 109: 647–655.LinkGoogle Scholar7 Trion A, de Maat MP, Jukema JW, van der LA, Maas MC, Offerman EH, Havekes LM, Szalai AJ, Princen HM, Emeis JJ. No effect of C-reactive protein on early atherosclerosis development in apolipoprotein E*3-leiden/human C-reactive protein transgenic mice. Arterioscler Thromb Vasc Biol. 2005; 25: 1635–1640.LinkGoogle Scholar8 Falsey AR, Walsh EE, Francis CW, Looney RJ, Kolassa JE, Hall WJ, Abraham GN. Response of C-reactive protein and serum amyloid A to influenza A infection in older adults. J Infect Dis. 2001; 183: 995–999.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Frers R, Otero-Losada M, Kersberg E, Cosentino V and Capani F (2017) Immune System Links Psoriasis-Mediated Inflammation to Cardiovascular Diseases via Traditional and Non-Traditional Cardiovascular Risk Factors An Interdisciplinary Approach to Psoriasis, 10.5772/intechopen.68559 CSAJBOK L, NYLÉN K, ÖST M, SONANDER H and NELLGÅRD B (2015) In-hospital C-reactive protein predicts outcome after aneurysmal subarachnoid haemorrhage treated by endovascular coiling, Acta Anaesthesiologica Scandinavica, 10.1111/aas.12441, 59:2, (255-264), Online publication date: 1-Feb-2015. Kölliker Frers R, Bisoendial R, Montoya S, Kerzkerg E, Castilla R, Tak P, Milei J and Capani F (2015) Psoriasis and cardiovascular risk: Immune-mediated crosstalk between metabolic, vascular and autoimmune inflammation, IJC Metabolic & Endocrine, 10.1016/j.ijcme.2015.01.005, 6, (43-54), Online publication date: 1-Mar-2015. Kumaresan P, Devaraj S, Huang W, Lau E, Liu R, Lam K and Jialal I (2013) Synthesis and Characterization of a Novel Inhibitor of C-Reactive Protein–Mediated Proinflammatory Effects, Metabolic Syndrome and Related Disorders, 10.1089/met.2012.0123, 11:3, (177-184), Online publication date: 1-Jun-2013. Koenig W (2013) High-sensitivity C-reactive protein and atherosclerotic disease: From improved risk prediction to risk-guided therapy, International Journal of Cardiology, 10.1016/j.ijcard.2013.07.113, 168:6, (5126-5134), Online publication date: 1-Oct-2013. Bisoendial R, Boekholdt S, Vergeer M, Stroes E and Kastelein J (2010) C-reactive protein is a mediator of cardiovascular disease, European Heart Journal, 10.1093/eurheartj/ehq238, 31:17, (2087-2091), Online publication date: 1-Sep-2010. Döcke W, Asadullah K, Belbe G, Ebeling M, Höflich C, Friedrich M, Sterry W and Volk H (2008) Comprehensive biomarker monitoring in cytokine therapy: heterogeneous, time-dependent, and persisting immune effects of interleukin-10 application in psoriasis, Journal of Leukocyte Biology, 10.1189/jlb.0408249, 85:3, (582-593), Online publication date: 1-Mar-2009. Huang G, Luo C, Gu X, Wu Z, Wang Z, Du Z, Hu C and Tang L (2009) Mechanical Strain Induces Expression of C-Reactive Protein in Human Blood Vessels, Journal of Pharmacology and Experimental Therapeutics, 10.1124/jpet.109.150961, 330:1, (206-211), Online publication date: 1-Jul-2009. Bisoendial R, Birjmohun R, Akdim F, van ‘t Veer C, Spek C, Hartman D, de Groot E, Bankaitis-Davis D, Kastelein J and Stroes E (2009) C-Reactive Protein Elicits White Blood Cell Activation in Humans, The American Journal of Medicine, 10.1016/j.amjmed.2008.11.032, 122:6, (582.e1-582.e9), Online publication date: 1-Jun-2009. VAN LEUVEN S, BIRJMOHUN R, FRANSSEN R, BISOENDIAL R, DE KORT H, LEVELS J, BASSER R, MEIJERS J, KUIVENHOVEN J, KASTELEIN J and STROES E (2009) ApoAI-phosphatidylcholine infusion neutralizes the atherothrombotic effects of C-reactive protein in humans, Journal of Thrombosis and Haemostasis, 10.1111/j.1538-7836.2008.03175.x, 7:2, (347-354), Online publication date: 1-Feb-2009. Singh S, Suresh M, Voleti B and Agrawal A (2009) The connection between C‐reactive protein and atherosclerosis, Annals of Medicine, 10.1080/07853890701749225, 40:2, (110-120), Online publication date: 1-Jan-2008. 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Sheriff A, Kayser S, Brunner P and Vogt B (2021) C-Reactive Protein Triggers Cell Death in Ischemic Cells, Frontiers in Immunology, 10.3389/fimmu.2021.630430, 12 Bock C, Vogt B, Mattecka S, Yapici G, Brunner P, Fimpel S, Unger J and Sheriff A (2020) C-Reactive Protein Causes Blood Pressure Drop in Rabbits and Induces Intracellular Calcium Signaling, Frontiers in Immunology, 10.3389/fimmu.2020.01978, 11 Wallukat G, Mattecka S, Wenzel K, Schrödl W, Vogt B, Brunner P, Sheriff A and Kunze R (2022) C-Reactive Protein (CRP) Blocks the Desensitization of Agonistic Stimulated G Protein Coupled Receptors (GPCRs) in Neonatal Rat Cardiomyocytes, Journal of Clinical Medicine, 10.3390/jcm11041058, 11:4, (1058) December 9, 2005Vol 97, Issue 12 Advertisement Article InformationMetrics https://doi.org/10.1161/01.RES.0000196746.75724.8bPMID: 16339489 Originally publishedDecember 9, 2005 PDF download Advertisement