Role of ACE/ACE2 imbalance on cardiac fibrosis induced by diabetes

Objective To confirm the effects of angiotensin-converting enzyme (ACE)/ACE2 imbalance on cardiac fibrosis induced by diabetes mellitus and the regulatory effects of the PI3K/Akt/mTOR signaling pathways on cardiac fibrosis. Methods Diabetic rats induced by streptozocin and db/db diabetic mice were used to establish models of cardiac fibrosis induced by diabetes. The myocardial collagen area percentage was detected by Masson staining. The levels of ACE, ACE2, Akt, p-Akt, mammalian target of rapamycin (mTOR) and p-mTOR were measured by immunohistochemistry and Western blot. The contents of angiotensin Ⅱ (AngⅡ) and Ang-(1-7) were examined by enzyme-linked immunosorbent assay. Results Both diabetic rats and db/db mice presented obvious fibrosis in myocardial tissue and increased percentages of collagen area (P<0.05). Compared with the normal group, the contents of ACE and Ang Ⅱ significantly increased in the two diabetic models (P< 0.05). Notably, diabetic rats showed substantial decreases in ACE2 and Ang - (1-7), while increases were found as to ACE2 and Ang - (1-7) in db/db mice (P<0.05). Compared with the normal group, both diabetic rats and db/db mice produced remarkable increased ratios of ACE/ACE2 (P<0.05) as wll as p-Akt/Akt and p-mTOR/mTOR (P<0.05). Conclusions Diabetes mellitus induces the imbalance of ACE/ACE2 that stimulates the signaling pathway of PI3K/Akt/mTOR, leading to the diabetic cardiac fibrosis.