Circulating monocytes and cardiac macrophages in diastolic dysfunction (Mus musculus)

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1Endothelial cellMacrophageLeft ventriculardiastolic dysfunctionCollagen depositionAutocrine activationDecreased proteases / MMPsBloodCcl2ROSIl10Spp1MyofibroblastFibroblastROSROSIl10MonocyteFibroblastactivationMyocardiumMonocyteCcr2Adhesionmolecules


This pathway is modeled based on fig 10 in Hulsmans et al, and was developed in collaboration with Dr. Matthias Nahrendorf. Circulating monocytes and myocardial macrophage density are increased in diastolic dysfunction, and the macrophage expansion is partially driven by monocyte recruitment. Mechanistically, cardiac macrophages produce more IL-10 leading to autocrine activation toward a fibrogenic phenotype. A profibrotic macrophage subset secretes more Spp1 (OPN) and fewer proteases and MMPs, contributing to fibroblast activation, collagen deposition, and subsequently increased myocardial stiffness and diastolic dysfunction. (Description based on figure 10 legend).

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  1. Hulsmans M, Sager HB, Roh JD, Valero-Muñoz M, Houstis NE, Iwamoto Y, Sun Y, Wilson RM, Wojtkiewicz G, Tricot B, Osborne MT, Hung J, Vinegoni C, Naxerova K, Sosnovik DE, Zile MR, Bradshaw AD, Liao R, Tawakol A, Weissleder R, Rosenzweig A, Swirski FK, Sam F, Nahrendorf M; ''Cardiac macrophages promote diastolic dysfunction.''; J Exp Med, 2018 PubMed Europe PMC Scholia


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102094view00:18, 29 November 2018KhanspersModified title
102093view00:14, 29 November 2018KhanspersModified description
102091view22:14, 28 November 2018KhanspersOntology Term : 'hypertension' added !
102090view22:14, 28 November 2018KhanspersOntology Term : 'myofibroblast cell' added !
102089view22:13, 28 November 2018KhanspersOntology Term : 'cardiovascular system disease' added !
102088view22:13, 28 November 2018KhanspersOntology Term : 'macrophage' added !
102087view22:13, 28 November 2018KhanspersOntology Term : 'monocyte' added !
102086view22:12, 28 November 2018KhanspersNew pathway

External references


NameTypeDatabase referenceComment
Ccl2GeneProductENSMUSG00000035385 (Ensembl)
Ccr2GeneProductENSMUSG00000049103 (Ensembl)
Il10GeneProductENSMUSG00000016529 (Ensembl)
ROSMetaboliteCHEBI:26523 (ChEBI)
Spp1GeneProductENSMUSG00000029304 (Ensembl)

Annotated Interactions

No annotated interactions

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