Cargando…
5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction
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), rem...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308004/ https://www.ncbi.nlm.nih.gov/pubmed/34300270 http://dx.doi.org/10.3390/jcm10143104 |
_version_ | 1783728178137661440 |
---|---|
author | Popp, Sandy Schmitt-Böhrer, Angelika Langer, Simon Hofmann, Ulrich Hommers, Leif Schuh, Kai Frantz, Stefan Lesch, Klaus-Peter Frey, Anna |
author_facet | Popp, Sandy Schmitt-Böhrer, Angelika Langer, Simon Hofmann, Ulrich Hommers, Leif Schuh, Kai Frantz, Stefan Lesch, Klaus-Peter Frey, Anna |
author_sort | Popp, Sandy |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8308004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83080042021-07-25 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 J Clin Med Article 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. MDPI 2021-07-14 /pmc/articles/PMC8308004/ /pubmed/34300270 http://dx.doi.org/10.3390/jcm10143104 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Popp, Sandy Schmitt-Böhrer, Angelika Langer, Simon Hofmann, Ulrich Hommers, Leif Schuh, Kai Frantz, Stefan Lesch, Klaus-Peter Frey, Anna 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction |
title | 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction |
title_full | 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction |
title_fullStr | 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction |
title_full_unstemmed | 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction |
title_short | 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction |
title_sort | 5-htt deficiency in male mice affects healing and behavior after myocardial infarction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308004/ https://www.ncbi.nlm.nih.gov/pubmed/34300270 http://dx.doi.org/10.3390/jcm10143104 |
work_keys_str_mv | AT poppsandy 5httdeficiencyinmalemiceaffectshealingandbehavioraftermyocardialinfarction AT schmittbohrerangelika 5httdeficiencyinmalemiceaffectshealingandbehavioraftermyocardialinfarction AT langersimon 5httdeficiencyinmalemiceaffectshealingandbehavioraftermyocardialinfarction AT hofmannulrich 5httdeficiencyinmalemiceaffectshealingandbehavioraftermyocardialinfarction AT hommersleif 5httdeficiencyinmalemiceaffectshealingandbehavioraftermyocardialinfarction AT schuhkai 5httdeficiencyinmalemiceaffectshealingandbehavioraftermyocardialinfarction AT frantzstefan 5httdeficiencyinmalemiceaffectshealingandbehavioraftermyocardialinfarction AT leschklauspeter 5httdeficiencyinmalemiceaffectshealingandbehavioraftermyocardialinfarction AT freyanna 5httdeficiencyinmalemiceaffectshealingandbehavioraftermyocardialinfarction |