Abstract
Background: During myocardial infarction (MI), billions of cardiomyocytes are lost. The optimal therapy should effectively replace damaged cardiomyocytes, possibly with stem cells able to engraft and differentiate into adult functional cardiomyocytes. As such, cardiac atrial appendage stem cells (CASCs) are suitable candidates. However, the presence of elevated levels of advanced glycation end products (AGEs) in cardiac regions where CASCs are transplanted may affect their regenerative potential. In this study, we examine whether and how AGEs alter CASCs properties in vitro. Methods and Results: CASCs in culture were exposed to ranging AGEs concentrations (50 µg/mL to 400 µg/mL). CASCs survival, proliferation, and migration capacity were significantly decreased after 72 h of AGEs exposure. Apoptosis significantly increased with rising AGEs concentration. The harmful effects of these AGEs were partially blunted by pre-incubation with a receptor for AGEs (RAGE) inhibitor (25 µM FPS-ZM1), indicating the involvement of RAGE in the observed negative effects. Conclusion: AGEs have a time- and concentration-dependent negative effect on CASCs survival, proliferation, migration, and apoptosis in vitro, partially mediated through RAGE activation. Whether anti-AGEs therapies are an effective treatment in the setting of stem cell therapy after MI warrants further examination.
Highlights
Coronary heart disease (CHD) remains the leading cause of mortality and morbidity worldwide, with myocardial infarction (MI) being the most common form of CHD [1]
The negative impact of advanced glycation end products (AGEs) on cardiac atrial appendage stem cells (CASCs) proliferation was concentraAs shown in Figure 1, AGEs significantly and gradually decreased CASCs proliferation tion-dependent
The negative impact of AGEs on CASCs proliferation was concentrationAGEs significantly reduced CASCs proliferation compared to bovine serum albumin (BSA)
Summary
Coronary heart disease (CHD) remains the leading cause of mortality and morbidity worldwide, with myocardial infarction (MI) being the most common form of CHD [1]. Oxygen and nutrients are restricted, resulting in myocardial cell death. The infarct size depends on multiple factors, such as the size of the ischemic area at risk, the location and duration of coronary occlusion, and the amount of residual collateral blood flow [1,2]. Finding a therapeutic approach that effectively replaces myocardial scar with functional contractile tissue is the only option to recover lost cardiac tissue. The optimal therapy should effectively replace damaged cardiomyocytes, possibly with stem cells able to engraft and differentiate into adult functional cardiomyocytes. Conclusion: AGEs have a time- and concentration-dependent negative effect on CASCs survival, proliferation, migration, and apoptosis in vitro, partially mediated through RAGE activation. Whether anti-AGEs therapies are an effective treatment in the setting of stem cell therapy after MI warrants further examination
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.
