Epidemiology has associated fine particulate matter(PM_(2.5))exposure with an increased cardiovascular risk.However,the underlying mechanism,particularly from the liver perspective,remains unclear.Here,the influence o...Epidemiology has associated fine particulate matter(PM_(2.5))exposure with an increased cardiovascular risk.However,the underlying mechanism,particularly from the liver perspective,remains unclear.Here,the influence of chronic PM_(2.5)exposure on cardiovascular risk in mice fed a high-fat and high-cholesterol diet(HFCD)was studied by using a real-world PM_(2.5)exposure system.Results showed that PM_(2.5)exposure elevated the serum levels of nonhigh-density lipoprotein cholesterol(non-HDL-C)and oxidized low-density lipoprotein(oxLDL)in HFCD-fed mice,demonstrating increased cardiovascular risk.To investigate the molecular mechanism,lipidomics and metabolomics analyses were conducted and revealed that PM_(2.5)exposure enhanced lipid accumulation and disturbed purine metabolism and glutathione metabolism in the liver of HFCD-fed mice,contributing to the elevated non-HDL-C levels and intensified oxidative stress.Moreover,PM_(2.5)exposure increased total cholesterol levels by upregulating Hmgcr expression and downregulating Cyp7a1 expression in the livers of HFCD-fed mice.The HDL-C level was reduced by inhibiting the hepatic Abca1 and Abcg1 expression and decreasing the levels of ApoA-I and LCAT.Additionally,the PM_(2.5)-induced pro-oxidative environment impeded the oxLDL clearance and further triggered inflammation,in turn exacerbating oxidative stress and oxLDL production.This study demonstrated a synergy of PM_(2.5)and HFCD on cardiovascular risk and illuminated the molecular mechanism in PM_(2.5)-susceptible populations.展开更多
基金supported by National Key Research and Development Program of China(2018YFA0901104)National Natural Science Foundation of China(91843301)+1 种基金Hong Kong General Research Fund(12302922,12303320,and 12103820)internal research funds SKLP_2223_P04 from Hong Kong Baptist University.
文摘Epidemiology has associated fine particulate matter(PM_(2.5))exposure with an increased cardiovascular risk.However,the underlying mechanism,particularly from the liver perspective,remains unclear.Here,the influence of chronic PM_(2.5)exposure on cardiovascular risk in mice fed a high-fat and high-cholesterol diet(HFCD)was studied by using a real-world PM_(2.5)exposure system.Results showed that PM_(2.5)exposure elevated the serum levels of nonhigh-density lipoprotein cholesterol(non-HDL-C)and oxidized low-density lipoprotein(oxLDL)in HFCD-fed mice,demonstrating increased cardiovascular risk.To investigate the molecular mechanism,lipidomics and metabolomics analyses were conducted and revealed that PM_(2.5)exposure enhanced lipid accumulation and disturbed purine metabolism and glutathione metabolism in the liver of HFCD-fed mice,contributing to the elevated non-HDL-C levels and intensified oxidative stress.Moreover,PM_(2.5)exposure increased total cholesterol levels by upregulating Hmgcr expression and downregulating Cyp7a1 expression in the livers of HFCD-fed mice.The HDL-C level was reduced by inhibiting the hepatic Abca1 and Abcg1 expression and decreasing the levels of ApoA-I and LCAT.Additionally,the PM_(2.5)-induced pro-oxidative environment impeded the oxLDL clearance and further triggered inflammation,in turn exacerbating oxidative stress and oxLDL production.This study demonstrated a synergy of PM_(2.5)and HFCD on cardiovascular risk and illuminated the molecular mechanism in PM_(2.5)-susceptible populations.
