PM2.5 induced cardiac hypertrophy via CREB/GSK3b/SOS1 pathway and metabolomics alterations

Area of Science:

• Environmental Health
• Cardiovascular Research
• Pharmacology

Background:

• Fine particulate matter (PM2.5) exposure is linked to adverse cardiovascular effects, including cardiac hypertrophy and impaired function.
• PM2.5 can adsorb toxic substances, leading to pulmonary gas exchange interference and systemic inflammation.
• Cardiac hypertrophy, characterized by structural remodeling and fibrosis, is a significant risk factor for heart failure.

Purpose of the Study:

• To investigate the cardioprotective effects of low molecular weight (LMW) fucoidan against PM2.5-induced cardiac hypertrophy.
• To evaluate the impact of LMW fucoidan on cardiac function, structure, and related molecular pathways.
• To assess the clearance and metabolic effects of LMW fucoidan in organs affected by PM2.5 exposure.

Main Methods:

• Induction of cardiac hypertrophy in mice via PM2.5 exposure.
• Administration of LMW fucoidan for 28 consecutive days.
• Assessment of cardiovascular parameters including blood pressure, QT interval, and cardiac structure (echocardiography, histology).
• Analysis of protein expression (SOS1, CREB, GSK3b, GRB2) and metabolic alterations in serum and various organs.

Main Results:

• PM2.5 exposure led to increased blood pressure, prolonged QT interval, cardiac hypertrophy, and fibrosis.
• LMW fucoidan treatment significantly reduced myocardial injury, improved cardiac function, and reversed structural remodeling.
• Fucoidan administration altered protein expression, notably reducing CREB levels, and mitigated metabolic disturbances caused by PM2.5.
• Clearance effects of fucoidan were observed in serum, heart, kidney, lung, and liver.

Conclusions:

• LMW fucoidan demonstrates significant cardioprotective effects against PM2.5-induced cardiac hypertrophy and dysfunction.
• Fucoidan treatment rescues QT interval prolongation, improves cardiac structure, and reduces fibrosis.
• This study highlights the potential of LMW fucoidan as a therapeutic agent for mitigating cardiovascular damage from air pollution.