As ApoE−/− mice generate atherosclerotic lesions repeatedly at susceptible locations, particular at branch points of the aorta26, 27, we examined whether overexpressing HtrA2 is therapeutic and reduces aortic plaque progression in ApoE−/− mice immunized with proteoglycan to induce a hyperlipidemia-based RA animal model. Here, HTRA2 is linked to hyperlipidemia.