Periodontitis-related myocardial fibrosis by expansion of collagen-producing SiglecF+ neutrophils.
Summary
In multi-cohort human data and complementary mouse models, persistent periodontitis worsened post-MI remodeling via expansion of a GM-CSF/TGFβ–PPARγ–driven SiglecF+ neutrophil subset that deposits collagen and activates fibroblasts. Depletion of SiglecF+ neutrophils mitigated myocardial fibrosis, linking oral health to cardiac repair outcomes.
Key Findings
- Persistent, not short-term, periodontitis worsened post-MI fibrosis and function in humans and mice.
- Bone marrow neutrophils in PD were skewed towards longer-lived SiglecF+ neutrophils via GM-CSF/TGFβ in a PPARγ-dependent manner.
- SiglecF+ neutrophils deposited collagen and activated fibroblasts in infarcted hearts; depleting them reduced fibrosis.
Clinical Implications
Screening and management of periodontitis should be integrated into MI care pathways. Targeting SiglecF+ neutrophil pathways (e.g., GM-CSF/TGFβ–PPARγ signaling, local depletion strategies) may offer novel antifibrotic therapies.
Why It Matters
This study identifies a previously unrecognized collagen-producing neutrophil program as a driver of cardiac fibrosis after MI and establishes a mechanistic link between periodontitis and adverse cardiac remodeling.
Limitations
- Causality in humans is inferred; interventional human trials are lacking
- Potential sex/species differences (male mouse data emphasized) and unmeasured confounding in cohorts
Future Directions
Test oral-health interventions and neutrophil-targeted strategies to reduce post-MI fibrosis; validate SiglecF+ neutrophil biomarkers for risk stratification.
Study Information
- Study Type
- Cohort
- Research Domain
- Pathophysiology
- Evidence Level
- III - Prospective human cohort data complemented by mechanistic animal experiments without randomized human intervention
- Study Design
- OTHER