Complement Cross Talks With H-K-ATPase to Upregulate Runx2 in Human Aortic Valve Interstitial Cells

Area of Science:

• Cardiovascular Biology
• Cellular Pathophysiology
• Molecular Medicine

Background:

• Calcific aortic valve disease (CAVD) is a complex, progressive disorder.
• The complement system and H-K-ATPase are implicated in CAVD pathogenesis.
• Complement upregulates Runx2, promoting fibrosis in aortic valve interstitial cells (AVICs).

Purpose of the Study:

• To investigate the crosstalk between complement and H-K-ATPase in regulating Runx2 in human AVICs.
• To elucidate the role of ERK1/2 signaling in this interaction.
• To identify potential therapeutic targets for CAVD.

Main Methods:

• Human AVICs were isolated from normal and calcified valves.
• Cells were treated with complement, H-K-ATPase, or ERK1/2 inhibitors.
• Expression levels and signaling pathways were analyzed using RT-PCR, immunofluorescence, and Western blot.

Main Results:

• Calcified AVICs showed higher H-K-ATPase levels than normal AVICs.
• Complement treatment increased H-K-ATPase and Runx2 expression in AVICs, activating ERK1/2 signaling.
• Inhibiting H-K-ATPase or ERK1/2 blocked complement-induced Runx2 upregulation.

Conclusions:

• Complement and H-K-ATPase interact to upregulate Runx2 in human AVICs through ERK1/2 activation.
• H-K-ATPase plays a significant role in CAVD pathogenesis.
• Targeting the complement system or H-K-ATPase offers potential therapeutic strategies for CAVD.