Novel Murine Model of Atherosclerosis Progression Induced by a Modified Paigen Diet

Background/Objectives: To better understand the mechanisms involved in atherosclerosis, different models have been developed, but these fail when studying the progression of this disease. The purpose of this study was to standardize a new model of atherosclerosis progression in rats using Paigen-type modified atherogenic diet. Methods: The design included a control group (n = 16) and 64 rats with atherogenic Paigen-type diet subdivided into four subgroups with different doses (Athero 1, Athero 2, Athero 3, and Athero 4). The atherogenic diet was supplemented orally in sequential stages: 1) Hypervitaminic (1.5 mL/kg/day for 12 days) and 2) Hyperlipidic (48 days ad libitum). Blood pressure, heart rate, aortic histopathology, inflammatory biomarkers, and biochemical lipid and liver profiles were measured in all groups on days 30 and 60. Results: All Athero 1 rats were sacrificed due to a poisoning for vitamin D2 excess. Athero 2 rats were sacrificed at day 30 showing severe atherosclerotic lesions (grades V-VIII). Athero 3 rats showed mild lesions (I-IV) at day 30 and severe lesions (V-VIII) at day 60. Athero 4 rats showed mild lesions (I-IV) at days 30 and 60. Diet-dependent changes in blood pressure and heart rate were observed. Furthermore, glycemia, dyslipidemia, and liver profile were associated with the degree of atherosclerotic lesion. Conclusions: "Athero 3" atherogenic diet generates a stable model to study the progress of atherosclerosis in rats.