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

S. Popp, A. Schmitt-Bohrer, S. Langer, U. Hofmann, L. Hommers, K. Schuh, S. Frantz, K.P. Lesch, A. Frey*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)

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 naive 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-beta, TNF-alpha, 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.

Original languageEnglish
Article number3104
Number of pages23
JournalJournal of Clinical Medicine
Volume10
Issue number14
DOIs
Publication statusPublished - 1 Jul 2021

Keywords

  • chronic heart failure
  • myocardial infarction
  • serotonin transporter deficient mice
  • anxiety
  • depression
  • behavior
  • inflammation
  • LEFT-VENTRICULAR RUPTURE
  • CORONARY-ARTERY-DISEASE
  • SEROTONIN TRANSPORTER
  • MATRIX METALLOPROTEINASES
  • DEPRESSION
  • LACKING
  • ANXIETY
  • RECEPTOR
  • MOUSE
  • INFLAMMATION

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