DYRK1A overexpression decreases plasma lecithin:cholesterol acyltransferase activity and apolipoprotein A-I levels

Abstract

Background and aimsDown syndrome is caused by trisomy of all or part of human chromosome 21. Individuals with Down syndrome present some metabolic abnormalities involving lipoproteins, notably lower high-density lipoprotein levels associated with altered lecithin:cholesterol acyltransferase activity and apolipoprotein A-I levels. DYRK1A is a kinase overexpressed in Down syndrome that can activate the STAT3 pathway, which is involved in lecithin:cholesterol acyltransferase expression. Therefore, we characterized the role of DYRK1A overexpression on lecithin:cholesterol acyltransferase activity and expression in mouse models. MethodsEffects of Dyrk1a overexpression were examined in mice overexpressing Dyrk1a by ELISA, chemical analyses and Western blotting. ResultsOverexpression of DYRK1A decreased plasma lecithin:cholesterol acyltransferase activity and hepatic STAT3 activation, which was associated with activation of SHP2, a tyrosine phosphatase. Although hepatic apolipoprotein E and D levels were increased in mice overexpressing DYRK1A, decreased plasma lecithin:cholesterol acyltransferase activity was associated with decreased hepatic and plasma apolipoprotein A-I levels. High-density lipoprotein-cholesterol levels were also decreased in plasma despite similar total cholesterol and non-high-density lipoprotein-cholesterol levels. ConclusionsWe identified the role of DYRK1A overexpression on altered lipoprotein metabolism.