Cross-talk between the complement system and endothelial cells in physiologic conditions and in vascular diseases

Fischetti, Fabio; Tedesco, Francesco

doi:10.1080/08916930600739712

Cited by 81 publications

(72 citation statements)

References 146 publications

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“…In the case of DECs, we failed to detect immunoglobulins and C4 co-localized with C1q suggesting that C activation through the classical pathway is unlikely to be responsible for the binding of C1q to ECs. This observation is in agreement with the findings that quiescent cultured ECs do not activate C (Mold and Morris, 2001) or support a very low C activation (Hindmarsh and Marks, 1998;Yin et al, 2007) and is consistent with the antiinflammatory property of the endothelium maintained by cell surface and plasma C inhibitors (Fischetti and Tedesco, 2006).…”

Section: Discussionsupporting

confidence: 81%

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Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium

Bulla

Agostinis

Bossi

et al. 2008

Molecular Immunology

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112

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This study was prompted by the observation that decidual endothelial cells (DECs), unlike endothelial cells (ECs) of blood vessels in normal skin, kidney glomeruli and brain, express surface-bound C1q in physiologic pregnancy. This finding was unexpected, because deposits of C1q are usually observed in pathologic conditions and are associated with complement activation. In the case of DECs, we failed to detect immunoglobulins and C4 co-localized with C1q on the cell surface. Surprisingly, DECs expressed mRNA for the three chains of C1q and secreted detectable level of this component in serum-free medium. The ability to synthesize C1q is acquired by DECs during pregnancy and is not shared by ECs obtained from endometrium and from other sources. Cell-associated C1q has a molecular weight similar to that of secreted C1q and is released from DECs following treatment with heparinase or incubation at low pH. This suggests that C1q binds to DECs and it is not constitutively expressed on the cell surface. C1q is localized at contact sites between endovascular trophoblast and DECs and acts as an intercellular molecular bridge because adhesion of endovascular trophoblast to DECs was inhibited by antibodies to C1q and to a receptor recognizing its globular portion expressed on trophoblast.

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Section: Discussionsupporting

confidence: 81%

“…Endothelial cells (ECs) cover the inner surface of the vessel wall and establish continuous interaction with the complement (C) system that may cause their morphologic and functional changes (Fischetti and Tedesco, 2006).…”

Section: Introductionmentioning

confidence: 99%

Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium

Bulla

Agostinis

Bossi

et al. 2008

Molecular Immunology

Self Cite

112

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“…Activated endothelial cells have been shown to secrete complement components and to express adhesion molecules ICAM‐1 and VCAM‐1 in response to sC5b‐9 and are also targets for complement activation products 44. Herein, we also found a significant correlation between sC5b‐9 and the adhesion molecules in the whole HF group, further suggesting crosstalk between endothelial cells and terminal complement activation in patients with acute, severe HF following MI.…”

Section: Discussionsupporting

confidence: 57%

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

et al. 2018

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AimsHeart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction.Methods and resultsThe LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary intervention‐treated ST‐elevation myocardial infarction herein underwent a post hoc analysis. Blood samples were drawn from inclusion to Day 5 and at 42 day follow‐up, and biomarkers were measured with enzyme immunoassays. Regional myocardial contractility was measured by echocardiography as wall motion score index (WMSI). The cardiogenic shock group (n = 9) was compared with the non‐shock group (n = 52). Controls (n = 44) were age‐matched and sex‐matched healthy individuals. C4bc, C3bc, C3bBbP, and sC5b‐9 were elevated in patients at inclusion compared with controls (P < 0.01). The shock group had higher levels compared with the non‐shock group for all activation products except C3bBbP (P < 0.05). At Day 42, all products were higher in the shock group (P < 0.05). In the shock group, sC5b‐9 correlated significantly with WMSI at baseline (r = 0.68; P = 0.045) and at Day 42 (r = 0.84; P = 0.036). Peak sC5b‐9 level correlated strongly with WMSI at Day 42 (r = 0.98; P = 0.005). Circulating endothelial cell activation markers sICAM‐1 and sVCAM‐1 were higher in the shock group during the acute phase (P < 0.01), and their peak levels correlated with sC5b‐9 peak level in the whole HF population (r = 0.32; P = 0.014 and r = 0.30; P = 0.022, respectively).ConclusionsComplement activation discriminated cardiogenic shock from non‐shock in acute ST‐elevation myocardial infarction complicated by HF and correlated with regional contractility and endothelial cell activation, suggesting a pathogenic role of complement in this condition.

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“…Complement has indeed been implicated in the activation and stimulation of endothelial cells (33), with the subsequent release of proangiogenic and prothrombotic factors (34). In this study, we have further investigated the mechanism of complement inhibition by Trx1 and demonstrated the presence of reduced Trx1 at the endothelial cell surface, suggesting a role in limiting cell surface complement deposition.…”

Section: Discussionmentioning

confidence: 93%

Truncated and Full-Length Thioredoxin-1 Have Opposing Activating and Inhibitory Properties for Human Complement with Relevance to Endothelial Surfaces

King

Nowakowska

Karsten

et al. 2012

The Journal of Immunology

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Thioredoxin (Trx)-1 is a small, ubiquitously expressed redox-active protein with known important cytosolic functions. However, Trx1 is also upregulated in response to various stress stimuli, is found both at the cell surface and secreted into plasma, and has known anti-inflammatory and antiapoptotic properties. Previous animal studies have demonstrated that exogenous Trx1 delivery can have therapeutic effects in a number of disease models and have implicated an interaction of Trx1 with the complement system. We found that Trx1 is expressed in a redox-active form at the surface of HUVEC and acts as an inhibitor of complement deposition in a manner dependent on its Cys-Gly-Pro-Cys active site. Inhibition occurred at the point of the C5 convertase of complement, regulating production of C5a and the membrane attack complex. A truncated form of Trx1 also exists in vivo, Trx80, which has separate nonoverlapping functions compared with the full-length Trx1. We found that Trx80 activates the classical and alternative pathways of complement activation, leading to C5a production, but the inflammatory potential of this was also limited by the binding of inhibitors C4b-binding protein and factor H. This study adds a further role to the known anti-inflammatory properties of Trx1 and highlights the difference in function between the full-length and truncated forms.

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Cross-talk between the complement system and endothelial cells in physiologic conditions and in vascular diseases

Cited by 81 publications

References 146 publications

Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium

Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

Truncated and Full-Length Thioredoxin-1 Have Opposing Activating and Inhibitory Properties for Human Complement with Relevance to Endothelial Surfaces

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