C-Reactive Protein in the Arterial Intima

Torzewski, Michael; Rist, Carsten; Mortensen, Richard F.; Zwaka, Thomas P.; Bienek, Magda; Waltenberger, Johannes; Köenig, Wolfgang; Schmitz, Gerd; Hombach, Vinzenz; Torzewski, Jan

doi:10.1161/01.atv.20.9.2094

Cited by 489 publications

(142 citation statements)

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“…This result was corroborated by RT‐PCR analysis (Figure 5A). It is well known, however, that most of the CRP within atherosclerotic lesions derives from plasma CRP insudation 24. We therefore performed extensive immunohistochemical studies using a well‐established mouse monoclonal anti‐CRP antibody 12, 13, 24, 25.…”

Section: Resultsmentioning

confidence: 99%

“…It is well known, however, that most of the CRP within atherosclerotic lesions derives from plasma CRP insudation 24. We therefore performed extensive immunohistochemical studies using a well‐established mouse monoclonal anti‐CRP antibody 12, 13, 24, 25. Surprisingly, besides increasing extracellular staining around calcified areas of grade 2 to 4 lesions (rather impressive in grade 4 lesions) as well as rare intracellular staining, we were not able to detect any extracellular staining in early lesions (Figure 5B, left panels).…”

Section: Resultsmentioning

confidence: 99%

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Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease

Twardowski

Cheng

Michaelsen

et al. 2015

JAHA

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BackgroundWe have demonstrated previously that enzymatically degraded low‐density lipoprotein (eLDL) is an essential causative component for the initiation of atherosclerosis. Here, we investigated the different stages of human aortic valve sclerosis for the presence of eLDL and effectors of the innate immune system, as well as the interaction of eLDL with isolated valvular interstitial cells/myofibroblasts to discover possible pathways leading to aortic valve sclerosis.Methods and ResultsHuman aortic valvular tissue was obtained from 68 patients undergoing valve replacement surgery. Patients were classified into 3 groups (mild, moderate, or severe aortic valve sclerosis), and clinical data for statistical analysis were gathered from all patients. Immunohistochemical staining demonstrated extensive extracellular deposits of eLDL throughout all grades of aortic valve sclerosis. Complementary analysis of lipid composition revealed higher concentrations of the decisive components of eLDL (ie, unesterified cholesterol and linoleic acid) compared with internal control tissues. Further, the complement component C3d and terminal complement complexes colocalized with eLDL compatible with the proposal that subendothelially deposited eLDL is enzymatically transformed into a complement activator at early stages of valvular cusp lesion development. Gene expression profiles of proteases and complement components corroborated by immunohistochemistry demonstrated an upregulation of the protease cathepsin D (a possible candidate for LDL degradation to eLDL) and the complement inhibitor CD55. Surprisingly, substantial C‐reactive protein expression was not observed before grade 2 aortic valve sclerosis as investigated with microarray analysis, reverse transcription–polymerase chain reaction analysis, and immunohistochemistry. Finally, we demonstrated cellular uptake of eLDL by valvular interstitial cells/myofibroblasts.ConclusionsThe present study is a startup of a hypothesis on the pathogenesis of aortic valve sclerosis declaring extracellular lipoprotein modification, subsequent complement activation, and cellular uptake by valvular interstitial cells/myofibroblasts as integral players.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease

Twardowski

Cheng

Michaelsen

et al. 2015

JAHA

Self Cite

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“…6 Moreover, it affects the synthesis and action of several inflammatory circulating mediators such as C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. 7,8 Epitopes of apolipoprotein B (apoB) 100 generated in association with LDL oxidation have been identified as major targets for immune responses in atherosclerosis. [9][10][11] Several studies have demonstrated increased titers of antibodies recognizing oxLDL in patients with coronary, 12 cerebral 13 or peripheral artery disease, 14 suggesting that they can serve as markers of the atherosclerotic process.…”

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confidence: 99%

Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy

Asciutto¹,

Dias²,

Edsfeldt³

et al. 2015

Atherosclerosis

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Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy.Asciutto, Giuseppe; Dias, Nuno; Edsfeldt, Andreas; Alm, Ragnar; Nordin Fredrikson, Gunilla; Goncalves, Isabel; Nilsson, Jan Link to publication Citation for published version (APA): Asciutto, G., Dias, N., Edsfeldt, A., Alm, R., Nordin Fredrikson, G., Goncalves, I., & Nilsson, J. (2015). Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy. Atherosclerosis, 239(2), 289-294. DOI: 10.1016289-294. DOI: 10. /j.atherosclerosis.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Methods: Native (nat) and malondialdehyde (MDA)-modified apoB p210 autoantibodies (IgM-p210nat, IgG-p210nat, IgM-p210MDA and IgG-p210MDA) were analyzed by ELISA from plasma samples of 351 patients at the time they underwent CEA. The incidence of postoperative CV events was assessed using national registers.Results: A total of 52 non-fatal and 15 fatal CV events were registered during the follow-up period (35.1 ± 16.7 months). Patients who suffered from a fatal CV event had significantly lower plasma levels of IgG-p210nat and IgG-p210MDA. Kaplan-Meier curves of event-free survival showed increased CV mortality in patients with levels of IgG-p210nat and IgGp210MDA below the median (Log Rank 7.813, p .005 and 9.105, p .003 respectively). The association between low levels of p210 IgG and fatal post-operative CV events remained significant when adjusting for age, sex, total cholesterol, HDL cholesterol, smoking habits and hypertension in a Cox Proportional Hazard model (hazard ratios (HR) IgG-p210nat below median: HR 6.7 (95% C.I. 1.5-30.6, p .013) and IgG-p210MDA below median: HR 7.8 (95% C.I. 1.7-35.5, p .008).Conclusions: The present findings support the notion that autoantibodies against LDL antigens are involved in the atherosclerotic disease process and suggest that CEA patients with low levels of IgG-p210nat and IgG-p210MDA have an increased risk of post-operative CV death.

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“…CRP protein elevation has been related with monocyte activation and adhesion molecules synthesis that recruit leukocytes 25 . In present study, IL-6 preceded CRP peak in the circulation and CRP peak was done at 24 hours after training.…”

Section: Discussionmentioning

confidence: 99%

Effect of elastic-band exercise on muscle damage and inflammatory responses in Taekwondo athletes

Gadruni

Mahmmadpour

Gadruni

2015

Rev Bras Med Esporte

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Introduction: Elastic bands offer variable elastic resistance (ER) throughout a range of motion and their incorporation with exercise movements has been used for variable strength training and rehabilitation purposes. Objective: Investigate the effect of acute bout of progressive elastic-band exercise on muscle damage and inflammatory response in Taekwondo athletes (TKD) compared with untrained ones. Methods: Fourteen (TKD, n = 7 and untrained, n = 7) men performed 3 sets of progressive resistance elastic exercise. Blood samples were taken pre-exercise and also immediately and 24h post exercise. Delayed onset muscle soreness (DOMS), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, total leukocyte counts, interleukin-6 and C-reactive protein (CRP) were analyzed. Results: Only DOMS increased in untrained group, but elevation of DOMS was observed in both groups (TKD and untrained) at 24h after exercise (p<0.05). CK and LDH activity increased in both groups significantly. Also TKD group only showed CK increasing 24h post exercise (p<0.05). Total circulating leukocyte counts increased immediately in post exercise experiments and decreased in 24h ones in both groups (p<0.05). Serum IL-6 immediately increased in both groups and 24h post exercises but there was no significant difference between immediate and 24h post exercise experiments in TKD group. Furthermore, CRP just increased 24h after exercise in both groups (p<0.05). Conclusion: Progressive resistance elastic exercise induced muscle damage and inflammation in TKD athletes, but also had smaller changes in comparison with untrained group and other forms of exercise.

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C-Reactive Protein in the Arterial Intima

Cited by 489 publications

References 44 publications

Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease

Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease

Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy

Effect of elastic-band exercise on muscle damage and inflammatory responses in Taekwondo athletes

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