5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction.
J Clin Med
; 10(14)2021 Jul 14.
Article
em En
| MEDLINE
| ID: mdl-34300270
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-ß, 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.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
J Clin Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha