PM2.5 Exacerbates Viral Myocarditis by Disrupting Lysophosphatidylcholine Metabolism and Inhibiting the...

Area of Science:

• Environmental Health
• Cardiovascular Biology
• Immunology

Background:

• Epidemiological studies associate fine particulate matter (PM2.5) with aggravated viral myocarditis (VMC).
• The precise mechanisms underlying PM2.5-induced VMC exacerbation remain incompletely understood.
• Lysophosphatidylcholine (LPC) metabolism and its signaling pathways are implicated in inflammatory responses.

Purpose of the Study:

• To investigate whether PM2.5 exposure exacerbates VMC by disrupting LPC metabolism and downstream signaling.
• To elucidate the role of the GPR4/ERK/PPARγ/TLR4 pathway in PM2.5-mediated cardiac inflammation.

Main Methods:

• A mouse model combining PM2.5 exposure and Coxsackievirus B3 (CVB3) infection was established.
• Cardiac function, inflammation, and molecular signaling were assessed using echocardiography, histology, and molecular techniques.
• In vitro studies utilized H9c2 cardiomyocytes exposed to PM2.5, LPC, GPR4 siRNA, and pathway inhibitors.

Main Results:

• PM2.5 exposure reduced LPC levels and downregulated its receptor GPR4 in vivo and in vitro.
• PM2.5 suppressed the ERK/PPARγ pathway, consequently releasing transcriptional inhibition of Toll-like receptor 4 (TLR4).
• GPR4 knockdown abolished LPC's effects on the ERK/PPARγ pathway and TLR4, confirming sequential signaling.

Conclusions:

• PM2.5 exacerbates VMC through a novel mechanism involving disrupted LPC metabolism.
• Inhibition of the GPR4/ERK/PPARγ pathway by PM2.5 leads to increased TLR4 activation and cardiac inflammation.
• The GPR4/ERK/PPARγ/TLR4 pathway represents a potential therapeutic target for mitigating PM2.5-associated myocardial damage.