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  <Comment Source="WikiPathways-description">This pathway is modeled based on fig 10 in [Hulsmans et al](https://www.ncbi.nlm.nih.gov/pubmed/29339450), 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).</Comment>
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      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">cardiovascular system disease</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">DOID:1287</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Disease</bp:Ontology>
    </bp:openControlledVocabulary>
    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">cardiovascular system disease</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">DOID:1287</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Disease</bp:Ontology>
    </bp:openControlledVocabulary>
    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">hypertension</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">DOID:10763</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Disease</bp:Ontology>
    </bp:openControlledVocabulary>
    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">intermediate monocyte</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">CL:0002393</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
    </bp:openControlledVocabulary>
    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">myofibroblast cell</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">CL:0000186</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
    </bp:openControlledVocabulary>
    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">myofibroblast cell</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">CL:0000186</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
    </bp:openControlledVocabulary>
    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">monocyte</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">CL:0000576</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
    </bp:openControlledVocabulary>
    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">hypertension</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">DOID:10763</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Disease</bp:Ontology>
    </bp:openControlledVocabulary>
    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">monocyte</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">CL:0000576</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
    </bp:openControlledVocabulary>
    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">disease pathway</bp:TERM>
      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PW:0000013</bp:ID>
      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pathway Ontology</bp:Ontology>
    </bp:openControlledVocabulary>
  </Biopax>
</Pathway>

