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

Popp, Sandy; Schmitt-Böhrer, Angelika; Langer, Simon; Hofmann, Ulrich; Hommers, Leif; Schuh, Kai; Frantz, Stefan; Lesch, Klaus-Peter; Frey, Anna

doi:10.3390/jcm10143104

Open AccessArticle

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

by

Sandy Popp

^1,2,†,

Angelika Schmitt-Böhrer

^3,†,

Simon Langer

¹,

Ulrich Hofmann

^1,4,5,

Leif Hommers

^3,5,

Kai Schuh

⁶

,

Stefan Frantz

^1,4,

Klaus-Peter Lesch

^1,2,3,7,8 and

Anna Frey

^1,4,5,*

¹

Comprehensive Heart Failure Center, University Hospital of Würzburg, 97078 Würzburg, Germany

²

Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, Division of Molecular Psychiatry, University Hospital of Würzburg, 97080 Würzburg, Germany

³

Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, 97080 Würzburg, Germany

⁴

Medical Clinic and Policlinic I, University Hospital of Würzburg, 97080 Würzburg, Germany

⁵

Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, 97080 Würzburg, Germany

⁶

Institute of Physiology I, University of Würzburg, 97070 Würzburg, Germany

⁷

Department of Translational Neuroscience, School for Mental Health and Neuroscience, Maastricht University, 6229 Maastricht, The Netherlands

⁸

Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally.

J. Clin. Med. 2021, 10(14), 3104; https://doi.org/10.3390/jcm10143104

Submission received: 3 June 2021 / Revised: 9 July 2021 / Accepted: 12 July 2021 / Published: 14 July 2021

(This article belongs to the Special Issue Effects of Stress and Psychological Trauma on the Development and Progression of Cardiovascular Diseases)

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Abstract

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 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.

Keywords: chronic heart failure; myocardial infarction; serotonin transporter deficient mice; anxiety; depression; behavior; inflammation

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MDPI and ACS Style

Popp, S.; Schmitt-Böhrer, A.; Langer, S.; Hofmann, U.; Hommers, L.; Schuh, K.; Frantz, S.; Lesch, K.-P.; Frey, A. 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction. J. Clin. Med. 2021, 10, 3104. https://doi.org/10.3390/jcm10143104

AMA Style

Popp S, Schmitt-Böhrer A, Langer S, Hofmann U, Hommers L, Schuh K, Frantz S, Lesch K-P, Frey A. 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction. Journal of Clinical Medicine. 2021; 10(14):3104. https://doi.org/10.3390/jcm10143104

Chicago/Turabian Style

Popp, Sandy, Angelika Schmitt-Böhrer, Simon Langer, Ulrich Hofmann, Leif Hommers, Kai Schuh, Stefan Frantz, Klaus-Peter Lesch, and Anna Frey. 2021. "5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction" Journal of Clinical Medicine 10, no. 14: 3104. https://doi.org/10.3390/jcm10143104

APA Style

Popp, S., Schmitt-Böhrer, A., Langer, S., Hofmann, U., Hommers, L., Schuh, K., Frantz, S., Lesch, K.-P., & Frey, A. (2021). 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction. Journal of Clinical Medicine, 10(14), 3104. https://doi.org/10.3390/jcm10143104

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

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