Changes of ACE and ACE2 expression in kidney of AGT-REN double transgenic hypertensive mice

AIM: To investigate the role of imbalance between angiotensin-converting enzyme (ACE) and ACE2 in hypertensive renal damage by observing the changes of ACE and ACE2 expression in angiotensinogen (AGT)-renin(REN) double transgenic hypertensive mice carrying both human AGT and REN genes. METHODS: Twenty-four male mice of 4 genotypes including wild-type (WT) mice, AGT transgenic mice, REN transgenic mice and AGT-REN double transgenic mice were used in this study. All animals were 10 months old. The carotid artery was catheterized for observation of mean arterial pressure (MAP). After an hour, the mice were killed. The left kidney was prepared for the paraffin fixation, sectioning and HE staining to observe the pathological changes. ACE/ACE2 expression in the kidney was detected by the method of immunohistochemistry. The right kidney was used for Western blotting. RESULTS: No significant difference between AGT transgenic mice and WT mice in MAP was observed(P>0.05). MAP was approximately 15 mmHg lower in REN transgenic mice than that in WT mice (P<0.05). However, MAP was approximately 30 mmHg higher in AGT-REN double transgenic mice than that in WT mice (P<0.05). Compared with WT mice, AGT and REN transgenic mice did not show obvious pathological change, and AGT-REN double transgenic mice showed significant pathological changes, including thickened arteriolar wall, narrow lumen, fibrinoid necrosis and hyalinization. The results of both immunohistochemisty and Western blotting showed that the expression of renal ACE in AGT-REN double transgenic mice was markedly increased, and the expression of ACE2 was significantly decreased, suggesting that the expression of ACE and ACE2 was significantly imbalanced in AGT-REN double transgenic mice. CONCLUSION: Double transgenic mice carrying both human AGT and REN genes show malignant hypertension, renal damage, and imbalance of ACE and ACE2 expression. The imbalance of ACE and ACE2 in the kidney may play an important role in the pathogenesis of hypertension.