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Stress is a potent risk factor for depression.Chronic stress can exacerbate and induce symptoms of depression.Clinical studies suggested that depressive patients are more likely to develop coronary artery diseases.However,the causal relationship between depression and heart failure progression remains unclear.In this study,we aimed to explore the relevance between stress and heart failure (HF) in a mouse model subjected to chronic restraint stress and left anterior descending coronary artery (LAD) ligation.Mice were restrained for 3 h daily for 21 days and the processes were repeated once 3 months later.After the repeated chronic restraint stress,mice showed dramatically increased immobility time in the forced swim test,indicating a state of despair.Restrained and control mice were further subjected to LAD ligation surgery.Echocardiography was conducted 1 week,2 weeks,and 1 month afterward.LAD-operated mice showed a significant decrease in the values of left ventricular ejection fraction (LVEF),and there was no difference in the LVEF values between the restrained and control mice.Relevant gene expression,neurotransmitter system,glial activation,and morphology of the heart-brain axis were comprehensively evaluated.We found no overall differences between the restrained and control mice with HF.Our results revealed that the repeated chronic restraint stress may have little effects on the progression of heart failure.