Key result
Exposure to ambient particulate matter induced myocardial hypertrophy and lipotoxicity in mice through PDGFRβ hypermethylation and downregulation of the MEK/ERK pathway, which was mitigated by PDGFRβ overexpression.
Why the study?
Particulate matter exposure can lead to myocardial hypertrophy, but PM-induced myocardial lipotoxicity and the specific role of PM-induced PDGFRβ methylation in hypertrophy and lipotoxicity remain unclear.
p-value: p=<0.05
PDGFRβ gene methylation is a potential biomarker for PM-induced myocardial hypertrophy, and its overexpression may prevent PM-induced cardiac hypertrophy and lipid metabolism disorders.
Animal data link PM to hypertrophy and lipotoxicity via PDGFRβ methylation; leaves open human relevance.
Background: PM exposure can lead to myocardial hypertrophy, with a potential contribution via DNA methylation. Myocardial lipotoxicity is closely related to myocardial hypertrophy. But, myocardial lipotoxicity caused by PM has not been reported. PDGFRβ, a platelet-derived growth factor receptor, is also essential for normal cardiovascular development. However, It is unclear the role of PM-induced PDGFRβ methylation in myocardial hypertrophy and myocardial lipotoxicity. We investigated the effect of PDGFRβ methylation induced by PM on myocardial hypertrophy and myocardial lipotoxicity. Results: PDGFRβ methylation caused by PM decreased PDGFRβ mRNA and protein expression in C57BL/6J mouse hearts. Thus inhibiting gene expression in its downstream pathway, ultimately leading to cardiac hypertrophy. Disturbances of myocardial lipid metabolism caused by PM in AC16 cells and C57BL/6J mouse hearts were also observed. High expression of PDGFRβ in neonatal rat primary cardiomyocytes was found to activate its downstream pathway and ameliorate the effects of PM-induced cardiac hypertrophic activity. At the same time, adenovirus was used to induce high expression of PDGFRβ in C57BL/6J mice. It was found that PDGFRβ not only improved PM-induced cardiac hypertrophy, but also alleviated PM-induced myocardial lipotoxicity. Conclusions: PDGFRβ gene methylation may be one of the potential biomarkers of myocardial hypertrophy induced by PM exposure. And high expression of PDGFRβ may be a potential way to prevent myocardial hypertrophy and cardiac lipid metabolism disorder caused by PM exposure in mice.
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Zhang et al. (2021) studied Myocardial hypertrophy and lipotoxicity (n=60). Particulate matter (PM) exposure vs. Filtered air or saline control was evaluated on Myocardial hypertrophy and PDGFRβ methylation (p=<0.05). Exposure to ambient particulate matter induced myocardial hypertrophy and lipotoxicity in mice through PDGFRβ hypermethylation and downregulation of the MEK/ERK pathway, which was mitigated by PDGFRβ overexpression.
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