Long-term social isolation during adolescence exacerbated cardiac dysfunction after myocardial infarction

Prolonged social isolation (SI) and negative emotion are associated with an increased risk of cardiovascular diseases (CVDs). However, it remains elusive whether SI and emotional states affect the pathological process of myocardial infarction (MI). In this study, SI models with different duration and MI model were co-established in mice. Anxiety and depression were assessed by a series of behavioral tests including open field test, elevated plus maze test, novelty-suppressed feeding test, tail suspension test and forced swim test. Cardiac function, heart infarct size and fibrosis were assessed by echocardiography, TTC staining, and Masson staining. The activity of neurons across the whole brain, as well as the hypothalamic-pituitary-adrenal (HPA) axis, was also investigated. Long-term SI induced anxiety and depression-like behaviors and aggravated cardiac injury and inflammatory response in MI mice, while short-term SI induced anxiety-like behavior but not depression-like behavior and had no significant effects on cardiac injury. Long-term SI altered the activity of several brain regions related to emotional, reward, autonomic and neuroendocrine regulation in MI mice. Furthermore, serum corticosterone levels were altered, indicating the potential involvement of HPA axis. These findings reveal that long-term SI exacerbated cardiac dysfunction and cardiac injury after MI. The underlying mechanisms involved in this process may include negative mood, dysregulation of the reward system, autonomic nervous system modulation, and HPA axis activation. These findings will contribute to our better understanding of heart-brain connections.