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

MC LOUGHLIN S; OTERO-LOSADA M.; RODRIGUEZ-GRANILLO G; MULLER A; OTTAVIANO G; MILEI J.

Paris

Congreso; ESC Congress 2011; 2011

European Society of Cardiology (ESC)

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 relationship bewtween hepatic damage and atherosclerotic development in apo E deficient mice over the first of 30 weeks of life. Methods: Fifteen Apo E-deficient mice were divided into 3 groups and euthanized at 16, 20 and 30 weeks of age. Aortic arch and liver were dissected for histomorphometric assessment. Hematoxylin-eosin and Heidenhain trichrome (Azan) staining were used for histological examination and acetic orcein staining allowed elastic fiber identification. After manual planimetry in a dedicated image analysis software, sections were magnified and digitalized. Plaque area and stenosis (%) were calculated. For liver histological analysis, non-alcoholic steato hepatitis (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±µm2 ± 58809µm2 vs 0 ±µm2 p<0,0001) and 20 weeks (124345µm2 ± 58809µm2 vs 24637µm2 ± 15394µm2 p<0,0001). Percent stenosis was also increased at 30 weeks of age as compared with 20 weeks (36,66% ± 19,81 vs. 13,10 % ± 8,8% p=0,01) and 16 weeks (36,66% ± 19,81 vs. 0% p=0,001). Predominant liver injury features for 16, 20 and 30 weeks were steatosis (3,75±0,5; 2,75 ± 0,95 and 3 ± 0) and hepatocellular injury (2,50 ± 0,57; 2,50 ± 1,29; 2,75 ± 0,5) in all groups and presented no significant differences with aging. Parenchymal inflammation scores were significantly increased at 30 weeks of age when compared to 16 and 20 weeks (1,5 ± 0,57 vs. 0 ± 0; p=0,001 and 1,5 ± 0,57 vs. 0,25 ± 0,50 p=0,003) as well as portal inflammation scores (0,5 ± 0,57 vs. 1,75 ± 0,5; p =0,008 ; 0,75 ± 0,5 vs 1,75 ± 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, liver inflammation presents a significant increase at 30 weeks as compared with 20 and 16 weeks but not between 16 to 20 weeks of age. This transition from steatosis to steatohepatitis is accompanied by a significant increase in plaque area also at 30 weeks of age but, likewise, not between 16 to 20 weeks. These data suggests that atherosclerotic evolution in Apo E-deficient mice might be related to the progression to a more severe inflammatory form of liver damage.