Characterising the role of Coronin-1A in developing atherosclerosis using the ApoE-/- Mouse Model

Background: Atherosclerosis is a disease in which build of plaques are build up inside the arteries composed of fat and cholesterol calcium. Atherosclerosis is the underlying cause of cardiovascular diseases.

Aim: Using a mouse in vivo model, we aim to examine whether the coronin-1A protein plays a role in developing atherosclerosis. We also aim to investigate whether coronin-1A is associated with sex differences in developing atherosclerosis.

Method: We will employ an established mouse model of atherosclerosis in which ApoE gene knockout mice (Apo-/-) develop atherosclerosis on a high fat diet. These mice have been crossed with coronin-1A -/- mice to produce either ApoE-/- single knockout controls and ApoE-/- ,Coro1a-/- double knockout (DKO) mice. The mice were fed high-fat diet for ten weeks and then culled for analysis in week 10. Specifically, the body and organs were weighed, blood samples were analysed for blood cell counts and tissues, including the heart aortic root were subjected to histological stains to assess disease progression and severity. In addition, circulating lipids were quantified in plasma samples from culled mice. Intraplaque compositions were quantified using histological staining to measure necrotic core, lipids, collagen content and total plaque burden.

Results: While male DKO mice were heavier in body weight, liver weight and abdominal fat compared to control ApoE-/- control mice, these differences were not seen in matched female DKO mice. There was a reduction of white blood cells in the DKO mice in both male and female groups. Platelets distribution width (PVW), mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased in the DKO mice in both male and female mice. Atherosclerotic plaques in the male DKO mice showed an increase in necrotic core size and lipid content? Compared to male ApoE-/- mice suggesting a more severe phenotype. In comparison, no while atherosclerotic