The complement component C5a is present in human coronary lesions
            <i>in vivo</i>
            and induces the expression of MMP‐1 and MMP‐9 in human macrophages
            <i>in vitro</i>

Speidl, Walter S.; Kastl, Stefan P.; Hutter, Randolph; Katsaros, Katharina M.; Kaun, Christoph; Bauriedel, Gerhard; Maurer, Gerald; Huber, Kurt; Badimón, Juan J.; Wojta, Johann

doi:10.1096/fj.10-156083

Cited by 82 publications

(78 citation statements)

References 39 publications

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“…Plaque destabilisation is brought about not only by matrix metalloproteinase (MMP)-expressing macrophages but also by mast cells. The levels and activity of MMP-1 and MMP-9 in human monocyte-derived macrophages were increased in vitro by the anaphylatoxin C5a, and C5a as well as MMP-1 and MMP-9 were found to be co-expressed in human atherectomy specimens [66] .…”

Section: Macrophages Express Complement Factors and Are Pathogenic Inmentioning

confidence: 92%

The Role of Complement in the Development and Manifestation of Murine Atherogenic Inflammation: Novel Avenues

Francescut

Steiner²,

Byrne³

et al. 2011

J Innate Immun

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Atherosclerosis is a chronic progressive inflammatory disease which manifests in the arterial vascular tree. It is a major cause of cardiovascular morbidity and contributes significantly to mortality in the developed world. Triggers for this inflammatory process are elevated levels of cholesterol, bacterial infection and obesity. The immune response in atherosclerosis is essentially pro-atherogenic, leading to lipid accumulation and cellular changes within the arterial wall. Small-animal models of atherosclerosis are used to study the relevance of candidate factors (cells, genes, diets) in the development and progression of lesions. From a multidisciplinary viewpoint, there are challenges and limitations to this approach. Activation of complement determines or modifies the outcome of acute and chronic inflammation. This review dissects the role of complement in the early development as well as the progressive manifestation of murine atherosclerosis and the advances in knowledge provided by the use of specific mouse models. It gives a critical overview of existing models, analyses seemingly conflicting results obtained with complement-deficient mouse models, highlights the importance of interrelationships between pro-coagulpant activity, adipose tissue, macrophages and complement, and uncovers exciting avenues of topical research.

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Section: Macrophages Express Complement Factors and Are Pathogenic Inmentioning

confidence: 92%

The Role of Complement in the Development and Manifestation of Murine Atherogenic Inflammation: Novel Avenues

Francescut

Steiner²,

Byrne³

et al. 2011

J Innate Immun

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“…In addition, activation of the complement system generates the anaphylatoxins C3a and C5a, which trigger proinflammatory signaling through their G protein-coupled receptors C3aR, C5aR1, and C5aR2, resulting in chemotaxis and several additional inflammatory responses (14). Circulating levels of C5a are increased in patients with advanced atherosclerotic lesions, and C5a has been suggested to play a role in matrix degradation leading to plaque rupture (15,16). Complement inhibition at several levels has been shown to reduce atherosclerosis in mice (17,18).…”

Section: Eposition Of Cholesterol-rich Lipoproteins In the Vesselmentioning

confidence: 99%

Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal–Induced Inflammatory Responses by Reducing Complement Activation

Niyonzima

Samstad

Aune

et al. 2015

The Journal of Immunology

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Chronic inflammation of the arterial wall is a key element in the development of atherosclerosis, and cholesterol crystals (CC) that accumulate in plaques are associated with initiation and progression of the disease. We recently revealed a link between the complement system and CC-induced inflammasome caspase-1 activation, showing that the complement system is a key trigger in CC-induced inflammation. HDL exhibits cardioprotective and anti-inflammatory properties thought to explain its inverse correlation to cardiovascular risk. In this study, we sought to determine the effect of reconstituted HDL (rHDL) on CC-induced inflammation in a human whole blood model. rHDL bound to CC and inhibited the CC-induced complement activation as measured by soluble terminal C5b-9 formation and C3c deposition on the CC surface. rHDL attenuated the amount of CC-induced complement receptor 3 (CD11b/CD18) expression on monocytes and granulocytes, as well as reactive oxygen species generation. Moreover, addition of CC to whole blood resulted in release of proinflammatory cytokines that were inhibited by rHDL. Our results support and extend the notion that CC are potent triggers of inflammation, and that rHDL may have a beneficial role in controlling the CC-induced inflammatory responses by inhibiting complement deposition on the crystals.

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“…Interferon-γ, eine lokale Komplementaktivierung, die verminderte Produktion beziehungsweise der vermehrte Abbau von Kollagen sowie die Apoptose glatter Muskelzellen spielen bei der akuten Plaqueruptur mit konsekutivem Auftreten eines Myokardinfarktes oder eines ischämischen Schlaganfalls eine große Rolle [3,4,5,6,7,8]. Die Pathophysiologie der Arteriosklerose und akuter Plaquerupturen ist vor dem Hintergrund der Komplexität immer noch Gegenstand aktueller Forschungsarbeiten.…”

Section: Hintergrundunclassified

Auswirkungen von obstruktiver Schlafapnoe und Tabakkonsum auf die endotheliale Funktion

Herkenrath¹

2016

Kompass Pneumol

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Hintergrund: Es ist bekannt, dass endotheliale Dysfunktion im Kontext von obstruktiver Schlafapnoe (OSA) oder Tabakkonsum auftreten kann. Die schädlichen Auswirkungen auf die vaskuläre Funktion bei gleichzeitigem Vorliegen beider Bedingungen sind hingegen weitgehend unbekannt. Ziel: Untersuchung der Frage, ob die Gleichzeitigkeit von OSA und Rauchen eine additive Schädigung im Hinblick auf endotheliale Dysfunktion bewirkt. Methoden: Eine männliche Population aus China ohne chronische innere Erkrankungen in der Vorgeschichte wurde gebeten, einen Fragebogen unter anderem zur Rauchexposition in Packungsjahren zu beantworten und sich einer Polysomnographie und einer peripheren arteriellen Tonometrie (PAT) zur Beurteilung der endothelialen Funktion zu unterziehen. Gemessen wurden die Serumwerte von 8-Isoprostan, AOPP (advanced oxidation protein products) und MCP-1 (monocyte chemo-attractant protein-1). Ergebnisse: 114 Männer wurden in die Studie eingeschlossen. Die PAT-Ratio, korrigiert für Alter und Body-Mass-Index, korrelierte invers mit dem Gesamt-Schweregrad der OSA: Apnoe-Hypopnoe-Index (AHI), r = -0,160 (p = 0,092); Sauerstoff-Entsättigungsindex, r = -0,214 (p = 0,024); Dauer der Sauerstoffsättigung <90%, r = -0,219 (p = 0,020) und Mindest-Sauerstoffsättigung, r = 0,250 (p = 0,008). Die PAT-Ratio sank mit steigender Zahl der Packungsjahre (p = 0,018). Sie war niedriger, wenn Raucheranamnese und mittelschwere bis schwere OSA (AHI ≥15/h) gleichzeitig vorlagen, als wenn nur einer oder keiner der Faktoren gegeben war (p = 0,011). Die Serumwerte von 8-Isoprostan und AOPP hingen positiv mit der Schwere der OSA zusammen, während MCP-1 mit der Quantität der Rauchexposition korrelierte. Multiple lineare Regressionsanalysen ergaben, dass die Schwere der intermittierenden Hypoxie, der MCP-1-Wert und die Zahl der Packungsjahre unabhängig Prognosefaktoren für die PAT-Ratio waren. Schlussfolgerung: Während OSA - insbesondere intermittierende Hypoxämie - und Rauchen für sich genommen schon unabhängige Risikofaktoren darstellten, war das gleichzeitige Vorliegen von mittelschwerer bis schwerer OSA und Tabakkonsum mit den schwersten Beeinträchtigungen der endothelialen Funktion assoziiert. Übersetzung aus Respiration 2016;91:124-131 (DOI:10.1159/000443527)

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The complement component C5a is present in human coronary lesions in vivo and induces the expression of MMP‐1 and MMP‐9 in human macrophages in vitro

Cited by 82 publications

References 39 publications

The Role of Complement in the Development and Manifestation of Murine Atherogenic Inflammation: Novel Avenues

The Role of Complement in the Development and Manifestation of Murine Atherogenic Inflammation: Novel Avenues

Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal–Induced Inflammatory Responses by Reducing Complement Activation

Auswirkungen von obstruktiver Schlafapnoe und Tabakkonsum auf die endotheliale Funktion

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