Type V collagen from macrophages regulates initial collagen assembly and alignment in post-infarcted hearts

Previous work has revealed that macrophages directly contribute collagen to the fibrotic scar in the injured hearts of zebrafish and mice. However, the functional impact of this contribution has not been investigated. Here, we characterised the deposition and ultrastructure of collagen fibrils in the forming scar of neonatal regenerative post-natal day (P)1 hearts and fibrotic P7 and adult mouse hearts after myocardial infarction (MI). Collagen type V (Col V) was the earliest deposited fibrillar collagen, coincident with macrophage recruitment to the site of injury and prior to cardiac myo-fibroblast activation. Deletion of COL5A1 in CD68+ macrophages resulted in disarrayed collagen fibrils within the nascent scar that was associated with a trend toward chamber dilation, wall thinning and compromised cardiac function. Our findings shed light on a role for macrophage-deposited Col V in establishing collagen deposition, alignment and scar stability prior to myofibroblast activation in the immediate acute phase post-MI.