Aortic damage, dyslipidemia and liver inflammation in atherosclerosis prone Apo-E knock-out mice.

OTERO-LOSADA M.; CUTRIN JC; RODRIGUEZ-GRANILLO G; MULLER A; OTTAVIANO G; MILEI J.

Athens

Congreso; EUROPEAN SOCIETY OF HYPERTENSION (ESH) AND INTERNATIONAL SOCIETY OF HYPERTENSION (ISH) JOINT MEETING.; 2014

Eur Society of Hypertension

Introduction: Chronology of atherosclerosis-related metabolic and pathological changes in ApoE-KO mice is not clear. Aim: to describe the chronology of biochemical alterations and liver and aorta histomorphology. Methods: Male ApoE-KO mice (C57BL/6 background) were fed with normal chow between the 16-30 weeks of life. After euthanasia, ascending aorta and liver cuts were processed for histomorphometry. Plasma was analyzed (enzymo-colorimetry). Results: glycemia increased at 20 weeks (+39%, p< 0.02) followed at 30 weeks by increase in TG (x2.8, p< 0.01), LDL-C (+62%, p< 0.05) and decrease in HDL-C (-26%, p< 0.05). Liver parenchymal inflammation (Par) and portal (Por) inflammation increased 4-fold (p< 0.01) and 2-fold (p< 0.03) respectively from weeks 20 to 30. Increases in aortic plaque area (Ao) (x5, p< 0.0001), stenosis percentage (x2.4, p< 0.01) and intima-media ratio (x3, p< 0.05) and media thinning (-69%, p< 0.01) were observed at 30 weeks. Hypertriglyceridemia accounted for 44% of Par (p< 0.007), 31% of Por (p< 0.03) and 31% of Ao increase (p< 0.03). Decrease in HDL-C explained 16% of Por (p< 0.03), 41% of the increase in intima: media ratio (p< 0.01) and 32% of Ao increase (p< 0.03). Decrease in relative HDL-C/TC accounted for 50% of Ao increase (p< 0.001). After controlling for Par, correlation between Ao and TG disappeared uncovering the role of liver inflammation in mediating TG effects on Ao while correlation between Ao and HDL-C decrease was strengthened (50% to 66% considering HDL-C/TC, r=0.812, p< 0.001), supporting a robust association between Ao and HDL-C. Increase in Ao was 52% explained by Par (p< 0.001). Conclusions: hyperglycemia preceded dyslipidemia. Present findings support the contribution of hypertriglyceridemia (indirectly via liver inflammation) and HDL-C decrease (directly) to aortic damage. Dyslipidemia association with hepatic and aortic pathology disappeared after controlling for life-time confirming the role of aging in these abnormalities.