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Prolylcarboxypeptidase protects from vascular dysfunction and promotes vascular repair

Adams, Gregory Nicholas
http://rave.ohiolink.edu/etdc/view?acc_num=case1346973249

Abstract Details

2013, Doctor of Philosophy, Case Western Reserve University, Pathology.
Prolylcarboxypeptidase (PRCP) is a cell surface protease that degrades peptides (including angiotensin II, des-Arg9-bradykinin and alpha-melanocyte stimulating hormone) and activates plasma prekallikrein. The enzyme is highly expressed by endothelial cells where it activates prekallikrein to liberate the vasoactive peptide bradykinin. The following studies characterize the vascular phenotype of the PRCP-deficient (PRCPgt/gt) mouse. Compared to wildtype animals, PRCPgt/gt are hypertensive and demonstrate faster times to induced arterial thrombotic occlusion. PRCPgt/gt have increased levels of vascular reactive oxygen species (ROS) and the hypertensive, prothrombotic phenotypes are corrected by oral antioxidant treatment. The vascular dysfunction induced by PRCP depletion was observed in vitro by siRNA treatment of endothelial cells. Additionally, PRCPgt/gt mice show signs of defective angiogenesis and vascular repair. The animals have decreased presence of vessels in sub-cutaneous injections of matrigel and decreased endothelial sprouting from excised aortic segments. Full thickness skin wounds from PRCPgt/gt heal slower than wildtype mice at the visual level and have decreased invasive blood vessel repair. PRCPgt/gt exhibit defective repair of large vessels as demonstrated by slow recovery from hind limb ischemia and thickened neo-intima formation following wire injury of the femoral artery. In sum, this work suggests PRCP protects from the pathological manifestations of vascular dysfunction and promotes angiogenesis and large vessel repair.
Alvin Schmaier, MD (Advisor)
Keith McCrae, MD (Committee Chair)
Mukesh Jain, MD (Committee Member)
Roy Silverstein, MD (Committee Member)
Clive Hamlin, Ph.D. (Committee Member)
120 p.
Biomedical Research; Pathology
hypertension; thrombosis; reactive oxygen species; ROS; endothelial; angiogenesis

Recommended Citations

Citations

  • Adams, G. N. (2013). Prolylcarboxypeptidase protects from vascular dysfunction and promotes vascular repair [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1346973249

    APA Style (7th edition)

  • Adams, Gregory. Prolylcarboxypeptidase protects from vascular dysfunction and promotes vascular repair. 2013. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1346973249.

    MLA Style (8th edition)

  • Adams, Gregory. "Prolylcarboxypeptidase protects from vascular dysfunction and promotes vascular repair." Doctoral dissertation, Case Western Reserve University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1346973249

    Chicago Manual of Style (17th edition)

case1346973249
327
© 2012, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.