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Loss of soluble gua...
Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation
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Mauersberger, C (author)
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Sager, HB (author)
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Wobst, J (author)
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Dang, TA (author)
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Lambrecht, L (author)
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Koplev, S (author)
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Stroth, M (author)
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Bettaga, N (author)
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Schlossmann, J (author)
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Wunder, F (author)
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Friebe, A (author)
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- Björkegren, JLM (author)
- Karolinska Institutet
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Dietz, L (author)
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Maas, SL (author)
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van der Vorst, EPC (author)
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Sandner, P (author)
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Soehnlein, O (author)
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Schunkert, H (author)
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Kessler, T (author)
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(creator_code:org_t)
- 2022-12-12
- 2022
- English.
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In: Nature cardiovascular research. - : Springer Science and Business Media LLC. - 2731-0590. ; 1:12, s. 1174-1186
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Abstract
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- Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here, by using histology, flow cytometry and intravital microscopy, we show that functional loss of sGC in platelets of atherosclerosis-prone Ldlr−/− mice contributes to atherosclerotic plaque formation, particularly via increasing in vivo leukocyte adhesion to atherosclerotic lesions. In vitro experiments revealed that supernatant from activated platelets lacking sGC promotes leukocyte adhesion to endothelial cells (ECs) by activating ECs. Profiling of platelet-released cytokines indicated that reduced platelet angiopoietin-1 release by sGC-depleted platelets, which was validated in isolated human platelets from carriers of GUCY1A1 risk alleles, enhances leukocyte adhesion to ECs. Importantly, pharmacological sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in atherosclerosis-prone Ldlr−/− mice. Therefore, pharmacological sGC stimulation might represent a potential therapeutic strategy to prevent and treat CAD.
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- By the author/editor
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Mauersberger, C
-
Sager, HB
-
Wobst, J
-
Dang, TA
-
Lambrecht, L
-
Koplev, S
-
show more...
-
Stroth, M
-
Bettaga, N
-
Schlossmann, J
-
Wunder, F
-
Friebe, A
-
Björkegren, JLM
-
Dietz, L
-
Maas, SL
-
van der Vorst, E ...
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Sandner, P
-
Soehnlein, O
-
Schunkert, H
-
Kessler, T
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show less...
- Articles in the publication
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Nature cardiovas ...
- By the university
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Karolinska Institutet