CD38 promotes angiotensin II-induced cardiac hypertrophy

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Cellular Signaling

Background:

• Cardiac hypertrophy is a key factor in heart failure, regulated by complex signaling pathways.
• CD38 knockout mice show resistance to oxidative stress and protection from ischemia-reperfusion injury.
• The specific role of CD38 in cardiac hypertrophy remains unexplored.

Purpose of the Study:

• To investigate the role and underlying mechanisms of CD38 in angiotensin II (Ang-II)-induced cardiac hypertrophy.
• To determine if CD38 influences key markers of cardiac hypertrophy and associated signaling pathways.

Main Methods:

• Utilized CD38 knockout and wild-type mice subjected to Ang-II infusion.
• Employed RNA interference (RNAi) to knockdown CD38 in Ang-II-stimulated H9c2 cells.
• Assessed cardiac hypertrophy, fibrosis, gene expression (ANF, BNP), reactive oxygen species (ROS), SIRT3, intracellular Ca2+ levels, and signaling pathways (NFATc4, ERK, AKT).

Main Results:

• CD38 knockout mice exhibited significantly less cardiac hypertrophy and fibrosis compared to wild-type mice under Ang-II stimulation.
• CD38 knockdown in H9c2 cells reduced ANF and BNP expression and ROS generation.
• CD38 knockdown led to elevated SIRT3 expression, decreased intracellular Ca2+ release, reduced NFATc4 nuclear translocation, and inhibited ERK/AKT phosphorylation.

Conclusions:

• CD38 plays a critical role in promoting cardiac hypertrophy.
• CD38 appears to mediate hypertrophy by inhibiting SIRT3 expression and activating the Ca2+-NFAT signaling pathway.
• Targeting CD38 may offer a novel therapeutic strategy for treating cardiac hypertrophy.