{"id":{"repo_id":"ohiolink","oai_identifier":"oai:etd.ohiolink.edu:case1346973249"},"canonical_url":"https://search.dev.ndltd.org/etd/ohiolink/oai:etd.ohiolink.edu:case1346973249","repository":{"repo_id":"ohiolink","name":"OhioLINK","base_url":"https://etd.ohiolink.edu/acprod/odb_etd/ws/oai/oai"},"display":{"title":"Prolylcarboxypeptidase protects from vascular dysfunction and promotes vascular repair","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Adams, Gregory Nicholas"],"institution":"Case Western Reserve University School of Graduate Studies","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Pathology","degree_department":null,"school":null,"contributors":["Schmaier, Alvin","McCrae, Keith"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-03-07","date_published":"2013-03-07","updated_at":"2026-07-24T03:35:52Z","subjects":["Biomedical Research","Pathology","hypertension","thrombosis","reactive oxygen species","ROS","endothelial","angiogenesis"],"languages":["English"],"rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://rave.ohiolink.edu/etdc/view?acc_num=case1346973249","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Schmaier, Alvin","McCrae, Keith"]},{"key":"dc:creator","label":"Author","values":["Adams, Gregory Nicholas"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-03-07"]},{"key":"dc:publisher","label":"Institution","values":["Case Western Reserve University School of Graduate Studies / OhioLINK"]},{"key":"dc:type","label":"Dc Type","values":["Electronic Thesis or Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pathology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Case Western Reserve University School of Graduate Studies"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biomedical Research","Pathology","hypertension","thrombosis","reactive oxygen species","ROS","endothelial","angiogenesis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://rave.ohiolink.edu/etdc/view?acc_num=case1346973249"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf","p.120","16.31 MB"]},{"key":"dc:title","label":"Title","values":["Prolylcarboxypeptidase protects from vascular dysfunction and promotes vascular repair"]}]}],"canonical_facts":{"dc:contributor":["Schmaier, Alvin","McCrae, Keith"],"dc:creator":["Adams, Gregory Nicholas"],"dc:date":["2013-03-07"],"dc:description":["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."],"dc:format":["application/pdf","p.120","16.31 MB"],"dc:identifier":["http://rave.ohiolink.edu/etdc/view?acc_num=case1346973249"],"dc:language":["English"],"dc:publisher":["Case Western Reserve University School of Graduate Studies / OhioLINK"],"dc:rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"dc:subject":["Biomedical Research","Pathology","hypertension","thrombosis","reactive oxygen species","ROS","endothelial","angiogenesis"],"dc:title":["Prolylcarboxypeptidase protects from vascular dysfunction and promotes vascular repair"],"dc:type":["Electronic Thesis or Dissertation"],"thesis:degree_discipline":["Pathology"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["Case Western Reserve University School of Graduate Studies"]},"updated_at":"2026-07-24T03:35:52Z"}