Neutrophils Modulate Fibroblast Function and Promote Healing and Scar Formation after Murine Myocardial Infarction.
Adelina CurajDavid SchumacherMihaela RusuMareike StaudtXiaofeng LiSakine SimsekyilmazVera JankowskiJoachim JankowskiAndreea Ramona DumitraşcuDerek J HausenloyAlexander SchuhElisa Anamaria LiehnPublished in: International journal of molecular sciences (2020)
Recruitment of neutrophils to the heart following acute myocardial infarction (MI) initiates inflammation and contributes to adverse post-infarct left ventricular (LV) remodeling. However, therapeutic inhibition of neutrophil recruitment into the infarct zone has not been beneficial in MI patients, suggesting a possible dual role for neutrophils in inflammation and repair following MI. Here, we investigate the effect of neutrophils on cardiac fibroblast function following MI. Methods and Results: We found that co-incubating neutrophils with isolated cardiac fibroblasts enhanced the production of provisional extracellular matrix proteins and reduced collagen synthesis when compared to control or co-incubation with mononuclear cells. Furthermore, we showed that neutrophils are required to induce the transient up-regulation of transforming growth factor (TGF)-ß1 expression in fibroblasts, a key requirement for terminating the pro-inflammatory phase and allowing the reparatory phase to form a mature scar after MI. Conclusion: Neutrophils are essential for both initiation and termination of inflammatory events that control and modulate the healing process after MI. Therefore, one should exercise caution when testing therapeutic strategies to inhibit neutrophil recruitment into the infarct zone in MI patients.
Keyphrases
- acute myocardial infarction
- left ventricular
- extracellular matrix
- transforming growth factor
- end stage renal disease
- oxidative stress
- heart failure
- ejection fraction
- chronic kidney disease
- newly diagnosed
- wound healing
- peritoneal dialysis
- epithelial mesenchymal transition
- poor prognosis
- induced apoptosis
- percutaneous coronary intervention
- physical activity
- emergency department
- coronary artery disease
- hypertrophic cardiomyopathy
- mitral valve
- aortic stenosis
- acute coronary syndrome
- binding protein
- patient reported
- cell death
- subarachnoid hemorrhage