The Role of ACE2 and Apelin in Cardiac and Vascular Diseases

  • Author / Creator
    Wang, Wang
  • Both ACE2 and apelin have been reported playing important roles in regulating cardiovascular structure and function. In this study, we used ACE2 or apelin gene knockout or knockdown mice to explore the roles of ACE2 or apelin in cardiovascular diseases. In particular, we created animal disease models of various cardiovascular remodeling or heart failure by exogenous Angiotensin II infusion or increasing the cardiac afterload or myocardial ischemia/infarction by surgeries. We also used ex vivo. disease models in isolated heart or vascular perfusion. Thereafter we performed cardiovascular morphological studies together with functional assays and signaling pathways studies. The results show that ACE2 is a protective factor against Ang II or transverse aortic constriction induced pathological remodeling by decreasing fibrosis, reactive oxygen species and direct degrading of Ang II. Apelin also shows beneficial effects in ischemic heart disease by promoting angiogenesis; apelin also counteracts Ang II by up-regulate ACE2 and mediates Ang II induced ACE2 up-regulation. In a separate group of studies, we confirmed that ACE2 degrades Apelin in vivo with significant functional changes. All these results added to the understanding of how ACE2 and apelin maintain the homeostasis of the cardiovascular system and the involvement in diseases conditions. Finally, we designed and tested apelin analogues; the results showing the potential of apelin, especially apelin analogues with C-terminal active and protected from ACE2 hydrolysis, as a new target for treating cardiovascular disease.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Physiology
  • Supervisor / co-supervisor and their department(s)
    • Oudit, Gavin (Medicine)
  • Examining committee members and their departments
    • Oudit, Gavin (Medicine)
    • O'Brien, Edward (Medicine)
    • Seubert, John (Pharmacology)
    • Kassiri, Zameneh (Physiology)
    • Lopaschuk, Gary (Pharmacology)