Given the portal vein hepatic first pass metabolism, the levels of D and DA prior to hydrolysis by Cyp 2C19, 3A4 and/or CES2 (Fig. 1C) could be high enough to directly inhibit liver ROCK1 to contribute to the anti-hyperlipidemia activity in the different animal models [87, 88] and in the human trial outcome [53]. Here, ROCK1 is linked to hyperlipidemia.