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Effects of recombinant angiotensin-converting enzyme 2 on renal caspase signaling and apoptosis in apolipoprotein E-deficient mice

ZHANG Zhen-zhou1, XU Ran1, CHANG Qing1, XU Ying-le1, JIN Hai-yan1,2, CHEN Lai-jiang1, SONG Bei1, ZHONG Jiu-chang11   

  1. 1.State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute of Hypertension, Shanghai 200025, China; 2. Department of Mental Health, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2016-08-29 Published:2016-08-31
  • Supported by:

    National Major Research Plan Training Program， 91339108；National Basic Research Program of China，2014CB542300；National Natural Science Foundation of China，81370362，81170246；Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support，20152509

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Abstract:

Objective · To investigate the alterations in renal caspase signaling and apoptosis in apolipoprotein E (ApoE)-knockout (KO) mice and the effects of recombinant angiotensin-converting enzyme 2 (rACE2) on these alterations. Methods · The ApoEKO mice aged 11- or 12-week were infused with 1.5 mg/kg of Ang Ⅱ and/or 2 mg/kg of recombinant ACE2 (rACE2) per day for 2 weeks. Alterations in renal caspase signaling and renal cell apoptosis were determined with Western blotting and TUNEL method, respectively. Results · The renal cell apoptosis level was elevated in the ApoEKO mice as compared with the wild-type controls. Ang Ⅱ infusion promoted the increases in systolic blood pressure, renal cell apoptosis, expressions of cleaved caspase-3 and cleaved caspase-8, and levels of plasma urea nitrogen and creatinine, which could be revered by rACE2 intervention. Conclusion · The rACE2 treatment can lower the elevated blood pressure induced by Ang Ⅱ in ApoEKO mice and significantly improve renal cell apoptosis and kidney function, which suggest that ACE2 has certain protective effect on atherosclerotic renal injury.

Key words: angiotensin-converting enzyme 2, apolipoprotein E, hypertension, apoptosis, renoprotection