Hydrogen Sulfide Ameliorated High Choline-Induced Cardiac Dysfunction by Inhibiting cGAS-STING-NLRP3 Inflammasome...

Area of Science:

• Cardiovascular Biology
• Metabolic Disease
• Inflammation Research

Background:

• High choline intake is linked to cardiovascular disease, but the underlying mechanisms are unclear.
• Trimethylamine N-oxide (TMAO) is a choline metabolite implicated in cardiovascular risk.
• Hydrogen sulfide (H2S) plays a role in cardiovascular health, but its involvement in choline-induced dysfunction needs investigation.

Purpose of the Study:

• To investigate the role of hydrogen sulfide (H2S) in high choline-induced cardiac dysfunction.
• To elucidate the molecular mechanisms linking high choline intake to heart problems.
• To explore the therapeutic potential of H2S in mitigating choline-related cardiac damage.

Main Methods:

• Mice were fed a high-choline diet for 4 months, with some receiving DMB to inhibit TMAO production or NaHS as an H2S donor.
• Echocardiography was used to assess cardiac function (ejection fraction and fractional shortening).
• Western blotting and ELISA were employed to measure protein levels of key inflammatory markers (cGAS, STING, NLRP3, caspase-1, IL-1β) and H2S-producing enzymes (CSE).

Main Results:

• High choline diet significantly reduced cardiac function (EF, FS) in mice.
• Choline or TMAO feeding increased the expression of cGAS, STING, NLRP3, caspase-1, and IL-1β, indicating inflammasome activation.
• Dietary choline decreased plasma H2S levels and increased CSE expression, while H2S supplementation (NaHS) improved cardiac function and reduced inflammasome markers.

Conclusions:

• High choline intake induces cardiac dysfunction by decreasing plasma H2S levels and activating the cGAS-STING-NLRP3 inflammasome axis.
• H2S plays a protective role against high choline-induced cardiac dysfunction.
• H2S treatment can restore cardiac function by inhibiting the cGAS-STING-NLRP3 inflammasome pathway.