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 language | English |
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Article number | 3104 |
Number of pages | 23 |
Journal | Journal of Clinical Medicine |
Volume | 10 |
Issue number | 14 |
DOIs | |
Publication status | Published - 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