Work

Serotonin 5-HT7 receptor signaling modulates inflammatory responses and survival after myocardial infarction

Year: 2026

Type: article

Abstract: BACKGROUND: Myocardial infarction (MI) is among the leading causes of death worldwide, and a precisely regulated inflammatory response is essential for effective cardiac repair and long-term outcome. The serotonergic system regulates immune cell functions, yet its contribution to post-MI remodeling is incompletely understood. METHODS: Here, we investigated the role of serotonin receptor 7 (5-HT7R) in post-infarction inflammation and outcome after permanent left anterior coronary artery ligation in mice, and complementary analysis of peripheral blood mononuclear cells (PBMCs) obtained from patients with acute MI. RESULTS: cells demonstrated high 5-HT7R expression in cardiac macrophages during the acute phase, which was confirmed by immunohistochemistry. Systemic 5-HT7R-knockout did not affect basal cardiac function but resulted in impaired left ventricular function and enhanced inflammatory signatures 14 days after MI without changes in infarct size. Pharmacological activation of 5-HT7R signaling with the selective agonist LP-211 increased survival after MI, although global systolic function among survivors was not improved. Transcriptomic profiling of cardiac macrophages 3 days after MI revealed bidirectional regulation of inflammatory and metabolic programs depending on 5-HT7R activity, including altered expression of Got1 and S100A9. Complementary, in PBMCs from MI patients Got1 expression was reduced, while S100A9 was increased, and both correlated with 5-HT7R expression. CONCLUSIONS: These data suggest 5-HT7R as a regulator of post-MI immune responses and a potential target to improve repair and survival.

Source: Journal of Translational Medicine

DOI: 10.1186/s12967-026-08423-4