HIF-1α/HO-1-Mediated Ferroptosis Participates in Polystyrene Nanoplastics-Induced Intergenerational Cardiotoxicity

Area of Science:

• Environmental Toxicology
• Cardiovascular Research
• Nanomaterial Safety

Background:

• Nanoplastics (PS-NP) pose emerging environmental and health risks.
• Understanding the intergenerational effects of nanoplastics is crucial for public health.
• Cardiotoxicity is a potential concern associated with plastic particle exposure.

Purpose of the Study:

• To investigate the intergenerational cardiotoxicity of polystyrene nanoplastics (PS-NP).
• To elucidate the underlying mechanisms of PS-NP-induced cardiotoxicity in offspring.
• To explore the role of hypoxia-inducible factor-1 (HIF-1) and ferroptosis.

Main Methods:

• Maternal mice were exposed to 60 nm PS-NP during pregnancy and lactation.
• Offspring heart tissues were analyzed for histological changes and cardiac biomarkers (CK-MB, LDH).
• RNA sequencing and KEGG analysis were performed to identify molecular pathways; ferroptosis markers and HIF-1α expression were assessed.

Main Results:

• PS-NP exposure in offspring hearts led to myocardial fiber disorder and cardiomyocyte degeneration.
• Elevated levels of creatine kinase isoenzymes (CK-MB) and lactate dehydrogenase (LDH) were observed.
• Mechanistic studies revealed PS-NP-induced ferroptosis, characterized by iron accumulation, mitochondrial damage, oxidative stress, GPX4 downregulation, and altered expression of FTH1, ACSL4, and SLC7A11.
• PS-NP upregulated HIF-1α and HO-1; inhibiting HIF-1α with si-HIF-1α alleviated PS-NP-induced ferroptosis.

Conclusions:

• Maternal exposure to PS-NP induces intergenerational cardiotoxicity in offspring.
• The mechanism involves HIF-1 and ferroptosis pathways.
• Targeting HIF-1α presents a potential strategy to mitigate PS-NP-induced cardiotoxicity.