Circulating monocytes and cardiac macrophages in diastolic dysfunction (WP4474)
Mus musculus
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).
For a description of pathway objects, see the WikiPathways Legend.
Authors
Kristina Hanspers , Martina Summer-Kutmon , and Daniela DiglesActivity
Discuss this pathway
Check for ongoing discussions or start your own.
Cited In
- Comparative Screening of the Liver Gene Expression Profiles from Type 1 and Type 2 Diabetes Rat Models (2024).
- Isoschaftoside in Fig Leaf Tea Alleviates Nonalcoholic Fatty Liver Disease in Mice via the Regulation of Macrophage Polarity (2025).
Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.
Organisms
Mus musculusCommunities
ExRNAAnnotations
Cell Type Ontology
macrophage macrophage intermediate monocyte myofibroblast cell myofibroblast cell monocyte monocyteDisease Ontology
cardiovascular system disease cardiovascular system disease hypertension hypertensionPathway Ontology
disease pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| ROS | Metabolite | chebi:26523 | |
| Ccl2 | GeneProduct | ensembl:ENSMUSG00000035385 | |
| Il10 | GeneProduct | ensembl:ENSMUSG00000016529 | |
| Spp1 | GeneProduct | ensembl:ENSMUSG00000029304 | |
| Ccr2 | GeneProduct | ensembl:ENSMUSG00000049103 |
References
- Cardiac macrophages promote diastolic dysfunction. Hulsmans M, Sager HB, Roh JD, Valero-Muñoz M, Houstis NE, Iwamoto Y, et al. J Exp Med. 2018 Feb 5;215(2):423–40. PubMed Europe PMC Scholia