Endothelial cells downregulate apolipoprotein D expression in mural cells through paracrine secretion and Notch...

Area of Science:

• Vascular Biology
• Cellular Communication
• Molecular Mechanisms

Background:

• Endothelial and mural cell interactions are crucial for blood vessel formation and function.
• Apolipoprotein D (APOD) is a secreted glycoprotein involved in stress response, lipid metabolism, and aging, and is found in atherosclerotic lesions.
• APOD influences smooth muscle cell regulation.

Purpose of the Study:

• To investigate the regulation of apolipoprotein D (APOD) in mural cells by endothelial cells.
• To elucidate the signaling pathways involved in APOD downregulation.
• To determine the functional consequences of APOD downregulation on mural cell behavior.

Main Methods:

• Coculture of endothelial and mural cells.
• Analysis of APOD gene expression.
• Investigation of Notch signaling pathways (NOTCH3, JAGGED-1).
• Assessment of mural cell adhesion and focal contact formation.

Main Results:

• Endothelial cells partially downregulate APOD expression in mural cells through paracrine secretion.
• Cell-contact dependent Notch signaling, specifically NOTCH3 on mural cells interacting with JAGGED-1 on endothelial cells, further downregulates APOD.
• NOTCH3 signaling is sufficient to attenuate APOD transcript expression.
• Decreased APOD expression in mural cells negatively regulates cell adhesion by reducing focal contacts, without affecting stress fiber formation.

Conclusions:

• Endothelial cells employ a novel mechanism to control mural cell function by downregulating APOD.
• This downregulation modulates mural cell adhesion, impacting vascular homeostasis.
• The interplay between endothelial cells, mural cells, and APOD represents a potential target for vascular disease therapies.