5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction

• Main Authors: Sandy Popp, Angelika Schmitt-Böhrer, Simon Langer, Ulrich Hofmann, Leif Hommers, Kai Schuh, Stefan Frantz, Klaus-Peter Lesch, Anna Frey
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Journal of Clinical Medicine
• Subjects: chronic heart failure; myocardial infarction; serotonin transporter deficient mice; anxiety; depression; behavior
• Online Access: https://www.mdpi.com/2077-0383/10/14/3104

Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either <i>5-Htt</i> genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.