Further invasive approaches to develop unstable plaques were aimed at generating hemodynamic changes both in ApoE−/− mice fed a high-fat diet, for example by placing a perivascular device [36,78] or introducing a tandem stenosis in the carotid arteries [38], and in ApoE−/− mice fed a standard diet, using two different interventions (ligation plus cuff positioning) on common carotid arteries [79,80] or using ligation of external and internal carotid arteries and part of the renal artery to induce hypertension [81]. This evidence concerns the gene APOE and hypertensive disorder.