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

MC LAUGHLIN SANTIAGO; OTERO-LOSADA, MATILDE; RODRIGUEZ-GRANILLO, GASTÓN; MULLER ANGÉLICA DEL CARMEN; OTTAVIANO G; MILEI J

Paris

Congreso; Congreso de la European Society of Cardiology; 2011

= = Abst=act Information Abstract Submitter: Doctor=/SPAN>  Ote=o-Losada  Ma=ilde - mol@fmed.uba.ar Event: ESC Congress 2011 Status: Submitted<=SPAN> Number: 88059 Title: Histopathol=gical study of lesion development in the aortic =rch and liver of apolipoprotein e-deficient =ice Evaluation Topic: 08.15 - Atherosclerosis Acro=ym Abbreviation: Acronym:<=TD> Category: Bench Options: = No Options   Abstract=20 Authors S. = Mc Loughlin1, M. Otero-Losada1, G. Rodriguez-Granillo1, A. Muller1, G. =ttaviano1, J. Milei1 - (1) Institute of =ardiological Research UBA-CONICET, Buenos Aires, Argentina   Abstract=20 Content 99%<=SPAN> Purpose: The chronological evolution of =therosclerotic lesions in apo E deficient mice is well established. However, hepatic injury =mplication in atherosclerotic development is still =nclear. This study explores explore the =elationship bewtween hepatic damage and =therosclerotic development in apo E deficient mice over =he first of 30 weeks of life. Methods: Fifteen =po E-deficient mice were divided into 3 =roups and euthanized at 16, 20 and 30 weeks of age. =ortic arch and liver were dissected for histomorphometric assessment. =ematoxylin-eosin and Heidenhain trichrome (Azan) staining =ere used for histological examination and acetic =rcein staining allowed elastic fiber =dentification. After manual planimetry in a dedicated =mage analysis software, sections were magnified =nd digitalized. Plaque area and stenosis (%) =ere calculated. For liver histological =nalysis, non-alcoholic steato hepatitis (NASH) =eatures were scored: steatosis (0-4), =epatocellular injury (0-4), parenchymal inflammation =0-4), portal inflammation (0-4) and fibrosis =0-4). Results: Significant increases in =laque area were observed at 30 weeks of age as =ompared with 16 weeks (124345±µm2 ± =8809µm2 vs 0 ±µm2 p<0,0001) and 20 weeks (124345µm2 =C2� 58809µm2 vs 24637µm2 ± 15394µm2 =<0,0001). Percent stenosis was also increased at 30 weeks of age as =ompared with 20 weeks (36,66% ± 19,81 vs. =3,10 % ± 8,8% p=0,01) and 16 weeks (36,66% ± =9,81 vs. 0% p=0,001). Predominant liver injury =eatures for 16, 20 and 30 weeks were steatosis =3,75±0,5; 2,75 ± 0,95 and 3 ± 0) and =epatocellular injury (2,50 ± 0,57; 2,50 ± 1,29; 2,75 ± =,5) in all groups and presented no significant differences with =ging. Parenchymal inflammation scores were =ignificantly increased at 30 weeks of age when compared =o 16 and 20 weeks (1,5 ± 0,57 vs. 0 ± =; p=0,001 and 1,5 ± 0,57 vs. 0,25 ± 0,50 ==0,003) as well as portal inflammation scores (0,5 ± =,57 vs. 1,75 ± 0,5; p =0,008 ; 0,75 ± 0,5 vs 1,75 =C2� 0,5 p=0,025). No fibrosis was detected in any group. Conclusion: Unlike atherosclerotic =laque area, hepatic steatosis is not increased =ith aging. However, liver inflammation =resents a significant increase at 30 weeks as =ompared with 20 and 16 weeks but not between 16 to 20 =eeks of age. This transition from steatosis to steatohepatitis is accompanied by a =ignificant increase in plaque area also at 30 weeks =f age but, likewise, not between 16 to 20 weeks. =hese data suggests that atherosclerotic =volution in Apo E-deficient mice might be related to =he progression to a more severe inflammatory =orm of liver damage. =/B>