Disease relevance of Soat2

• Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice [1].
• We have tested whether partial inhibition of ACAT1 and ACAT2 (expressed in liver and intestine) activities reduces atherosclerosis development in apoE-deficient mice and avoids toxicity [2].
• ACBP contains an endoplasmic reticulum retention motif and significantly colocalized with acyl-CoA cholesteryl acyltransferase 2 (ACAT2) and endoplasmic reticulum markers in L-cell fibroblasts and hepatoma cells, respectively [3].

High impact information on Soat2

• At 30 wk of age, only the control mice had significant atherosclerosis, which was nearly absent in ACAT2(-/-) ApoE(-/-) mice [4].
• Our results demonstrate the crucial role of ACAT2-derived cholesterol esters in the development of atherosclerosis in mice and suggest that triglyceride-rich apoB-containing lipoproteins are not as atherogenic as those containing cholesterol esters [4].
• Despite a lower level of ACAT activity, the ACAT1-expressing cells esterified 4-fold more sitosterol than the ACAT2 cells [5].
• Compared with ACAT1, ACAT2 selectively esterified cholesterol even when sitosterol was loaded into the microsomes [5].
• This sterol selectivity by ACAT2 may reflect a role in the sorting of dietary sterols during their absorption by the intestine in vivo [5].

Biological context of Soat2

• CONCLUSIONS: The increased hepatic CE levels, following P-407 treatment, was neither related to an up-regulation of ACAT2 nor enhanced SR-BI expression [6].
• Previous studies suggested the existence of several isoforms of ACAT with different tissue distribution and this has largely been confirmed by molecular cloning of ACAT-1 and ACAT-2 [7].

Associations of Soat2 with chemical compounds

• In contrast, ACAT2 demonstrated a strong preference for cholesterol rather than sitosterol [5].
• ASO-mediated knockdown of ACAT2 resulted in reduction of total plasma cholesterol, increased levels of plasma triglyceride, and a shift in LDL cholesteryl ester (CE) fatty acid composition from mainly saturated and monounsaturated to polyunsaturated fatty acid enrichment [8].
• The expression of acyl-coenzyme A:cholesterol acyltransferase 2 showed a sexually dimorphic response, where estrogen appeared to have a stimulatory effect in females, but not males [9].

Regulatory relationships of Soat2

• However, it has been found that cholesterol absorption is not completely inhibited in ACAT2-deficient (ACAT2 KO) mice [10].
• To support this idea, LDL that was modified to decrease its ability to induce net cellular cholesterol efflux stimulated ACAT 2-fold greater than control LDL when matched for lysosomal LDL-cholesterol influx [11].

Other interactions of Soat2

• The hepatic ACAT microsomal activity and ACAT2 protein expression were not altered by P-407 [6].
• Liver-specific inhibition of acyl-coenzyme a:cholesterol acyltransferase 2 with antisense oligonucleotides limits atherosclerosis development in apolipoprotein B100-only low-density lipoprotein receptor-/- mice [8].
• To test this hypothesis, cholesterol absorption was measured in mice deficient in both ABCA1 and ACAT2 (DKO) [10].

Analytical, diagnostic and therapeutic context of Soat2

• Northern blot analysis and real-time quantitative polymerase chain reaction data showed that ACAT-2 mRNA increased with age as well [12].

References