Lymphangiogenesis contributes to exercise-induced physiological cardiac growth

Area of Science:

• Cardiovascular Biology
• Lymphatic System Research
• Exercise Physiology

Background:

• Cardiac lymphangiogenesis is increasingly recognized for its beneficial effects on heart health.
• Exercise induces physiological cardiac growth, but the role of lymphangiogenesis in this process is not well understood.

Purpose of the Study:

• To investigate the role of cardiac lymphangiogenesis in exercise-induced physiological cardiac growth.
• To elucidate the underlying mechanisms, including the involvement of vascular endothelial growth factor receptor 3 (VEGFR3).

Main Methods:

• Mice underwent swimming exercise, with some treated with a VEGFR3 inhibitor (SAR131675).
• Lymphatic vessel density and expression of markers (LYVE-1, Podoplanin) were assessed.
• Cardiomyocyte proliferation and hypertrophy were studied using conditioned medium from lymphatic endothelial cells (LECs).

Main Results:

• Swimming exercise increased cardiac lymphangiogenesis and VEGFR3 expression.
• VEGFR3 inhibition attenuated exercise-induced cardiac growth and lymphangiogenesis.
• LEC-conditioned medium promoted cardiomyocyte hypertrophy and proliferation via AKT activation and the C/EBPβ-CITED4 axis.

Conclusions:

• Cardiac lymphangiogenesis, mediated by VEGFR3, is crucial for exercise-induced physiological cardiac growth.
• LECs promote cardiomyocyte growth through specific molecular signaling pathways, highlighting their importance in cardiac adaptation to exercise.