Abstract
Aim: 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.
Highlights
Following myocardial infarction (MI), a number of complex inflammatory and reparatory processes are initiated, which act to remove and replace necrotic heart tissue
We demonstrated that neutrophils and neutrophil-secreted mediators induced a significant increase in mRNA expression of fibronectin (Figure 2A) in isolated cardiac fibroblasts
Compared with the study of Horckmans et al, who demonstrated an important role of neutrophils in polarization of macrophages towards the reparatory phenotype [10], we have demonstrated in this study that neutrophils are actively involved in extracellular matrix formation, representing the key player in switching from the pro-inflammatory to anti-inflammatory phase after MI
Summary
Following myocardial infarction (MI), a number of complex inflammatory and reparatory processes are initiated, which act to remove and replace necrotic heart tissue. A persistent pro-inflammatory response can impair healing and contribute to adverse left ventricular (LV) remodeling after MI [1]. Neutrophils are recruited into the infarct zone immediately after MI onset, and their rapid degranulation and degradation have been shown to play a major pro-inflammatory role, contributing to an increase in MI size by inducing the death of cardiomyocytes at the border zone (so-called “neutrophil-induced injury”) [2], and impairing wound healing, resulting in adverse post-infarct LV modeling [3,4,5]. The persistence of neutrophils in the infarcted area has been reported to influence neither heart function nor infarct size [17]. There is a need to elucidate the role of neutrophils in healing and scar formation after MI in order to design effective therapeutic strategies for preventing adverse LV remodeling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
