AUTHOR=Solga Isabella , Şahin Aslihan , Yogathasan Vithya , Hofer Lina , Celik Feyza Gül , El Rai Amira , Hosen Mohammed Rabiul , Wischmann Patricia , Becher Stefanie , Polzin Amin , Gerdes Norbert , Jung Christian , Kelm Malte , Chennupati Ramesh 

TITLE=Acute blood loss anemia aggravates endothelial dysfunction after acute myocardial infarction

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1635293

DOI=10.3389/fcvm.2025.1635293

ISSN=2297-055X

ABSTRACT=BackgroundAnemia is frequently observed in patients with acute myocardial infarction (AMI) and is known to be associated with poor prognosis. We recently demonstrated that acute blood loss anemia is associated with a compensatory increase in endothelial nitric oxide (NO)-dependent flow-mediated dilation (FMD) responses. However, the effects of acute anemia on systemic endothelial function after AMI remain unclear. In this study, we evaluated systemic endothelial function following AMI in an established murine model of acute blood loss anemia. We hypothesize that acute anemia aggravates systemic endothelial dysfunction (ED) after AMI.Methods and resultsAcute anemia was induced in male C57BL/6J mice by repeated blood withdrawal for three consecutive days. Separate groups of anemic and non-anemic mice underwent AMI via left anterior descending artery (LAD) ligation (45 min), followed by reperfusion. Endothelial function was assessed using both in vivo and in vitro methods 24 h post-AMI. Impaired FMD (in vivo) and endothelium-dependent relaxation (EDR) responses were observed in the aorta, femoral, and saphenous arteries of AA mice compared to their respective control groups 24 h post-AMI. Analysis of oxidative products of NO in plasma revealed reduced nitrite and nitrate levels in acute anemia compared to controls 24 h post-AMI. Immunohistochemistry of aortic tissues from both anemic groups showed increased reactive oxygen species (ROS) product 4-Hydroxynonenal (4-HNE). Co-incubation of RBCs from anemic mice or anemic acute coronary syndrome (ACS) patients with aortic rings from wild-type mice demonstrated attenuated EDR responses. Supplementation with the ROS scavenger N-acetyl cysteine (NAC) for four weeks improved both in vivo and ex vivo EDR in acute anemic mice 24 h post-AMI.ConclusionAfter AMI, acute anemia is associated with ROS-mediated severe endothelial dysfunction, which is partly mediated by RBCs. Antioxidant supplementation with NAC is a potential therapeutic option to reverse the severe ED in anemia following AMI.