Evaluation of an experimental model of senescence SAMR1/SAMP8 for microRNA studies in acute myocardial infarction: role of sex and aging

Age and sex are critical yet often overlooked variables in preclinical models of acute myocardial infarction (AMI), potentially limiting the translational relevance of molecular findings. In this study, we used the Senescence-Accelerated Mouse Prone 8 (SAMP8) strain, a model of age-related cardiovascular dysfunction, alongside age-matched SAMR1 controls, to investigate early expression patterns of four canonical circulating miRNA biomarkers of AMI: miR-1-3p, miR-133a-3p, miR-208a-3p, and miR-499-5p. Male and female mice underwent left anterior descending (LAD) coronary artery ligation, with serum and cardiac tissue collected at 1, 4, and 24 h post-injury. Results reveal a robust early induction of all four miRNAs in serum, with 4 h identified as the optimal profiling time point. Notably, miR-1-3p was significantly elevated in both male and female SAMP8 mice post-AMI, but not in SAMR1. miR-133a-3p increased only in aged females, while male SAMP8 and SAMR1 mice showed divergent responses. miR-208a-3p and miR-499-5p rose consistently across all groups. In cardiac tissue, SAMR1 mice exhibited downregulation of all four miRNAs, whereas only miR-1-3p was reduced in SAMP8 males. Baseline expression in sham-operated hearts revealed age-related differences, particularly in males, with lower levels of miR-133a-3p, miR-208a-3p, and miR-499-5p in SAMP8 versus SAMR1. These findings highlight pronounced age- and sex-dependent miRNA expression dynamics in both serum and cardiac tissue during the acute phase of AMI. These results validate the SAMP8/SAMR1 model as a valuable tool for dissecting molecular responses to myocardial injury and underscore the need to integrate age and sex into preclinical AMI research.