Endothelial cell modulation of cardiomyocyte gene expression

Area of Science:

• Cardiovascular Biology
• Cellular Signaling
• Endothelial Cell Biology

Background:

• In vivo, microvascular endothelial cells and cardiomyocytes interact closely.
• Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are crucial for cardiac homeostasis.

Purpose of the Study:

• To investigate the paracrine signaling between cardiac microvascular endothelial cells and cardiomyocytes.
• To elucidate the role of endothelial cell-derived factors in regulating cardiomyocyte gene expression, particularly fetal genes.

Main Methods:

• In vitro co-culture of mouse atrial cardiomyocyte cell line (HL-1) and mouse cardiac microvascular endothelial cells.
• Treatment with endothelial cell-conditioned medium, endothelin-1 (ET-1), and angiopoietin-2 (Ang2).
• Assessment of ANP and BNP expression and release using molecular assays.
• Pharmacological inhibition of the calcineurin-NFAT pathway.

Main Results:

• Co-culture with endothelial cells or exposure to conditioned medium upregulated ANP and BNP expression in HL-1 cells.
• ET-1 stimulation of endothelial cells enhanced their paracrine effect on cardiomyocyte fetal gene expression.
• Angiopoietin-2 modulated ET-1-induced ANP expression in a concentration-dependent manner.
• Inhibition of the calcineurin-NFAT pathway blocked the stimulatory effect of conditioned medium on fetal gene expression.

Conclusions:

• Cardiac microvascular endothelial cells exert paracrine control over cardiomyocyte function.
• ET-1 signaling in endothelial cells influences cardiomyocyte fetal gene expression via paracrine pathways.
• Angiopoietin-2 and the calcineurin-NFAT pathway are involved in this endothelial-cardiomyocyte crosstalk.