Visualizing Cardiac Fibrosis: How Collagen Hybridizing Peptides (CHPs) Reveal Remodeling
Heart disease is the largest cause of death in the world. A major driver of heart disease is angiotensin II, a hormone that, if dysregulated, can trigger inflammation and fibrosis in the heart. Previously, it had been shown that CD14+ derived myeloid angiogenic cells (MACs) have the ability to drive angiogenesis. However, the utility of these MACs in reducing inflammation, and the method to include MACs into an inflammation-reducing state, was previously unknown. A recent paper in Scientific Reports showed that stimulating MACs with the cytokines M-CSF and IL-4 results in anti-inflammatory MACs (MIL4-MACs) that attenuate angiotensin II-driven heart failure in mice.
Standard histological collagen stains such as Picrosirius Red (PSR) measure total collagen, giving a picture of collagen accumulation and fibrotic scarring after it occurs. In this study, the authors needed a way to measure damaged collagen, as a readout of extracellular matrix remodeling. To address this, the authors used our Collagen Hybridizing Peptides (CHPs). Unlike tools that show the buildup of scar tissue, our CHPs provide a dynamic, real-time look at fibrotic remodeling by specifically binding to damaged collagen molecules.
Scarring of the heart tissue is a driver of heart failure and eventual death. Matrix Metalloproteinases (MMPs) including MMP-9 and MMP-2 are known to be expressed by macrophages. In order to compare the capacity of these macrophages to break down collagen, the researchers cultured fibroblasts to produce a collagen matrix. They then cultured M2 and MIL4-MAC macrophages on this collagen. Using F-CHP, the authors found that MIL4-MACs had a 4-fold greater capability to degrade collagen than M2 macrophages. This demonstrates the utility of MIL4-MACs at remodeling fibrotic areas.
The ability of CHPs to quantify fibrotic remodeling and damaged collagen is clearly outlined in this example of angiotensin II-driven heart disease. Using CHPs, the authors were able to highlight a unique capability of MIL4-MACs, as compared to M2 macrophages.
FULL PAPER: Kanayasu-Toyoda T, Tanaka T, Yoshihara K, Matsumura G, Hayashi K, Okura H, Matsuyama A, Uchida E, Yamaguchi T. Anti-inflammatory myeloid angiogenic cells (MIL4-MACs) attenuate angiotensin II‒induced heart failure in mice. Sci Rep. 2025 Oct 6;15(1):34809. doi: 10.1038/s41598-025-18702-7. PMID: 41053180; PMCID: PMC12501379.
