Histopathological study of lesion development in the aortic arch and lever of apolipoprotein e deficient mice

J MILEI; G RODRIGUEZ GRANILLO; M OTERO LOSADA; A MÜLLER; G OTTAVIANO; J MAC LAUGHLIN

París

Congreso; Congreso European Society of Cardiology; 2011

European Society of Cardiology

Histopathological studv of Iesion developrnent in the aortic arch andliver of apoüpoprotetn e-deficient miceS. Me Loughlin (Institute of Cardiological Research UBA-CONICET, Buenos Aires /Argentina), M. Otero-Losada (Institute of Cardiological Research UBA-CONICET, Buenos Aires /Argentina), G. Rodriguez-Granillo (Institute of Cardiological Research UBA-CONICET, Buenos Aires /Argentina), A. Muller (Instituteof Cardiological Research UBA-CONICET, Buenos Aires /Argentina), G. OUaviano (Institute of CardiologicalResearch UBA-CONICET, Buenos Aires /Argentina), J. Milei (Institute of Cardiological Research UBACONICET,Buenos Aires /Argentina)Purpose: The chronological evolution of atherosclerotic lesions in apo E deficient mice is well established. However,hepatic injury implication in atherosclerotic development is still unclear. This study explores explore the relationshipbewtween hepatic damage and atherosclerotic development in apo E deficient mice over the first of 30 weeks of lifeMethods: Fifteen Apo E-deficient mice were divided into 3 groups and euthanized at 16, 20 and 30 weeks of age.Aortic arch añd liver were dissected for histomorphometric assessment. Hematoxylin-eosin and Heidenhaintrichrome (Azan) staining were used for histological examination and acetic orcein staining allowed elastic fiberidentification. After manual planimetry in a dedicated image analysis software, sections were magnified anddigitalized. Plaque area and stenosis (%) were calculated. For liver histological analysis, non-alcoholic steatohepatitis (NASH) features were scored: steatosis (0-4), hepatocellular injury (0-4), parenchymal inflammation (0-4), portal inflammation (0-4) and fibrosis (0-4).Results: Significant increases in plaque area were observed at 30 weeks of age as compared with 16 weeks(124345±¡m2±58809¡m2 vs O ±¡m2 p<O,OOOl) and 20 weeks (124345¡m2±58809¡m2 vs 246371m2±153941m2p<O,OOOl). Percent stenosis was also increased at 30 weeks of age as compared with 20 weeks (36,66% ± 19,81vs. 13,10% ± 8,8% p=O,Ol) and 16 weeks (36,66% ± 19,81 vs. 0% p=O,OOl). Predominant liver injury featuresfor 16, 20 and 30 weeks were steatosis (3,75±´o,S; 2,75±0,95 and 3±0) and hepatocellular injury (2,SO±0,57;2,50±1,29; 2,75±0,5) in all groups and presented no significant differences with aging. Parenchymal inflammationscores were significantly increased at 30 weeks of age when compared to 16 and 20 weeks (1,5±0,57 vs. O±O;p=O,OOl and 1,S±0,57 vs. 0,25±0,SO p=0,003) as well as portal inflammation scores (0,S±0,57 vs. 1,7S±0,5;p=O,008; 0,75±0,S vs 1,7S±0,5 p=0,025). No fibrosis was detected in any group.Conclusion: Unlike atherosclerotic plaque area, hepatic steatosis is not increased with aging. However, liverinflammation presents a significant increase at 30 weeks as compared with 20 and 16 weeks but not between 16 to20 weeks of age. This transition from steatosis to steatohepatitis is accompanied by a significant increase in plaquearea also at 30 weeks of age but, likewise, not between 16 to 20 weeks. These data suggests that atheroscleroticevolution in Apo E-deficient mice might be related to the progression to a more severe inflammatory form of liverdamage.