Liver Plaques: Portal Vein Deposition of Oxidized Low-density Lipoprotein in Non-alcoholic Fatty Liver Disease

Abstract

ObjectivesThe interaction of accumulated oxidized low-density lipoprotein (oxLDL), a key pathogenic determinant of vascular atherosclerosis, with the hepatic microenvironment in non-alcoholic fatty liver disease (NAFLD) is unknown.MethodsWe aim to demonstrate the role of hepatic oxLDL deposition in the pathogenesis of NAFLD by immuno-fluoro-histo-chemistry. Cross-sectional human liver specimens of different stages of NAFLD (normal, fatty liver, hepatitis, and cirrhosis) were stained with antibodies against oxLDL, apolipoprotein B 100 (Apo-B 100), α smooth muscle actin (a marker of activated stellate cells), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD68 (a marker of Kupffer cell), and interleukin-1β (IL-1β) and compared in serial sections. OxLDL is confirmed by co-localized staining with Apo-B 100 and free cholesterol, which was stained with filipin.ResultsCompared to normal liver, oxLDL is deposited through the portal vein (rather than hepatic artery) in the early stage of NAFLD, forming plaques associated with Kupffer cell-related inflammation (marked by inducible expression of CD68, IL-1β and LOX-1) in the progressing stage. Further oxLDL accumulation extending to the hepatic sinusoid is closely associated with activated stellate cells in the cirrhosis stage.ConclusionsOxLDL-enriched portal plagues are closely associated with active inflammation and periportal fibrosis in the progression of NAFLD. Hepatic oxLDL deposition is of great significance in the pathogenesis of NAFLD and could be a potential useful clinical biomarker for the progression of NAFLD. ObjectivesThe interaction of accumulated oxidized low-density lipoprotein (oxLDL), a key pathogenic determinant of vascular atherosclerosis, with the hepatic microenvironment in non-alcoholic fatty liver disease (NAFLD) is unknown. The interaction of accumulated oxidized low-density lipoprotein (oxLDL), a key pathogenic determinant of vascular atherosclerosis, with the hepatic microenvironment in non-alcoholic fatty liver disease (NAFLD) is unknown. MethodsWe aim to demonstrate the role of hepatic oxLDL deposition in the pathogenesis of NAFLD by immuno-fluoro-histo-chemistry. Cross-sectional human liver specimens of different stages of NAFLD (normal, fatty liver, hepatitis, and cirrhosis) were stained with antibodies against oxLDL, apolipoprotein B 100 (Apo-B 100), α smooth muscle actin (a marker of activated stellate cells), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD68 (a marker of Kupffer cell), and interleukin-1β (IL-1β) and compared in serial sections. OxLDL is confirmed by co-localized staining with Apo-B 100 and free cholesterol, which was stained with filipin. We aim to demonstrate the role of hepatic oxLDL deposition in the pathogenesis of NAFLD by immuno-fluoro-histo-chemistry. Cross-sectional human liver specimens of different stages of NAFLD (normal, fatty liver, hepatitis, and cirrhosis) were stained with antibodies against oxLDL, apolipoprotein B 100 (Apo-B 100), α smooth muscle actin (a marker of activated stellate cells), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD68 (a marker of Kupffer cell), and interleukin-1β (IL-1β) and compared in serial sections. OxLDL is confirmed by co-localized staining with Apo-B 100 and free cholesterol, which was stained with filipin. ResultsCompared to normal liver, oxLDL is deposited through the portal vein (rather than hepatic artery) in the early stage of NAFLD, forming plaques associated with Kupffer cell-related inflammation (marked by inducible expression of CD68, IL-1β and LOX-1) in the progressing stage. Further oxLDL accumulation extending to the hepatic sinusoid is closely associated with activated stellate cells in the cirrhosis stage. Compared to normal liver, oxLDL is deposited through the portal vein (rather than hepatic artery) in the early stage of NAFLD, forming plaques associated with Kupffer cell-related inflammation (marked by inducible expression of CD68, IL-1β and LOX-1) in the progressing stage. Further oxLDL accumulation extending to the hepatic sinusoid is closely associated with activated stellate cells in the cirrhosis stage. ConclusionsOxLDL-enriched portal plagues are closely associated with active inflammation and periportal fibrosis in the progression of NAFLD. Hepatic oxLDL deposition is of great significance in the pathogenesis of NAFLD and could be a potential useful clinical biomarker for the progression of NAFLD. OxLDL-enriched portal plagues are closely associated with active inflammation and periportal fibrosis in the progression of NAFLD. Hepatic oxLDL deposition is of great significance in the pathogenesis of NAFLD and could be a potential useful clinical biomarker for the progression of NAFLD.