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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-242739
  • 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−/− miceAnxiety 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 5-Htt 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.show moreshow less

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Metadaten
Author: Sandy Popp, Angelika Schmitt-Böhrer, Simon Langer, Ulrich Hofmann, Leif Hommers, Kai Schuh, Stefan Frantz, Klaus-Peter Lesch, Anna Frey
URN:urn:nbn:de:bvb:20-opus-242739
Document Type:Journal article
Faculties:Medizinische Fakultät / Physiologisches Institut
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Medizinische Fakultät / Medizinische Klinik und Poliklinik I
Language:English
Parent Title (English):Journal of Clinical Medicine
ISSN:2077-0383
Year of Completion:2021
Volume:10
Issue:14
Article Number:3104
Source:Journal of Clinical Medicine 2021, 10(14), 3104; https://doi.org/10.3390/jcm10143104
DOI:https://doi.org/10.3390/jcm10143104
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:anxiety; behavior; chronic heart failure; depression; inflammation; myocardial infarction; serotonin transporter deficient mice
Release Date:2022/01/10
Date of first Publication:2021/07/14
Open-Access-Publikationsfonds / Förderzeitraum 2021
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International