Deficiency of acyl CoA:cholesterol acyltransferase 2 (ACAT2) in mice results in a reduction in cholesterol ester synthesis in the small intestine and liver, which in turn limits intestinal cholesterol absorption, hepatic cholesterol gallstone formation, and the accumulation of cholesterol esters in the plasma lipoproteins. Here we examined the contribution of ACAT2-derived cholesterol esters to atherosclerosis by crossing ACAT2-deficient (ACAT2 -/-) mice with apolipoprotein (apo) E-deficient (ApoE -/-) mice, an atherosclerosissusceptible strain that has impaired apoE-mediated clearance of apoB-containing lipoproteins. ACAT2 -/-ApoE -/-mice and ACAT2 ؉/؉ ApoE -/-(control) mice had similar elevations of plasma apoB and total plasma lipids; however, the lipid cores of the apoB-containing lipoproteins in ACAT2 -/-ApoE -/-mice contained primarily triglycerides rather than cholesterol esters. At 30 wk of age, only the control mice had significant atherosclerosis, which was nearly absent in ACAT2 -/-ApoE -/-mice. ACAT2 deficiency in the apoE-deficient background also led to a compensatory increase in the activity of lecithin͞cholesterol acyltransferase, the major plasma cholesterol esterification enzyme, which increased highdensity lipoprotein cholesterol esters. Our results demonstrate the crucial role of ACAT2-derived cholesterol esters in the development of atherosclerosis in mice and suggest that triglyceride-rich apoBcontaining lipoproteins are not as atherogenic as those containing cholesterol esters. Our results also support the rationale of pharmacological inhibition of ACAT2 as a therapy for atherosclerosis.
Gynecologic conditions in infants, children, and adolescents are distinct from those seen in adults, due to fluctuating hormone levels from infancy to puberty. This chapter focuses on the prepubertal child as there is significant overlap between gynecologic complaints in postpubertal adolescents and adults. The content in this chapter will enable emergency providers to distinguish normal pediatric gynecologic conditions from urgent and emergent pathology, including ovarian torsion, dysfunctional uterine bleeding and straddle injuries. Guidance for the management and treatment of these conditions is also provided in this chapter.
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