ELASTIN DEGRADATION IN THE AORTA OF WATANABE HEREDITARY HYPERLIPIDEMIC RABBITS

The Watanabe hereditary hyperlipidemic (WHHL) rabbit is an animal model that resembles humans with familial hyperlipidemia. In the thoracic aortae, there is also morphologic evidence of marked destruction of medial lamellar elastin fibers. Herein is provided the chemical evidence of elastolytic degradation. The levels of lysyl oxidase (L.Ox.), soluble elastin (SE) and insoluble elastin (IE) were estimated in thoracic aortae samples from New Zealand white (NZW) and WHHL rabbits at 6 months of age or 5 WHHL rabbits at 2.5 years of age. Enzyme-linked immunosorption assays (ELISA) were used in the L.Ox. and SE measurements. IE was measured following alkali extraction of aortae. There was a decrease in IE in thoracic aortae from Watanabe rabbits compared to NZW controls at 6 months of age (P < 0.1), and a further loss of IE in aortae from 2.5-year-old WHHL rabbits relative to the values at 6 months (P < 0.05). Average values for IE were: 130 mg/g for 6-month-old NZW, 100 mg/g for 6-month-old WHHL, and 60 mg/g for 2.5-year-old WHHL rabbits. Moreover, SE was only observed in aorta extracts from the older WHHL rabbits, a sign of elastolytic damage. There was also a five- to sixfold decrease in L.Ox. in the older vs. younger rabbits.