title: Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema.
abstract: Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor-associated angioedema. This case-control study tested the hypothesis that dipeptidyl peptidase IV activity and antigen are decreased in sera of patients with a history of angiotensin-converting enzyme inhibitor-associated angioedema. Fifty subjects with a history of angiotensin-converting enzyme inhibitor-associated angioedema and 176 angiotensin-converting enzyme inhibitor-exposed control subjects were ascertained. Sera were assayed for angiotensin-converting enzyme activity, aminopeptidase P activity, aminopeptidase N activity, dipeptidyl peptidase IV activity, and antigen and the ex vivo degradation half-lives of bradykinin, des-Arg(9)-bradykinin, and substance P in a subset. The prevalence of smoking was increased and of diabetes decreased in case versus control subjects. Overall, dipeptidyl peptidase IV activity (26.6+/-7.8 versus 29.6+/-7.3 nmol/mL per minute; P=0.026) and antigen (465.8+/-260.8 versus 563.1+/-208.6 ng/mL; P=0.017) were decreased in sera from individuals with angiotensin-converting enzyme inhibitor-associated angioedema compared with angiotensin-converting enzyme inhibitor-exposed control subjects without angioedema. Dipeptidyl peptidase IV activity (21.5+/-4.9 versus 29.8+/-6.7 nmol/mL per minute; P=0.001) and antigen (354.4+/-124.7 versus 559.8+/-163.2 ng/mL; P=0.003) were decreased in sera from cases collected during angiotensin-converting enzyme inhibition but not in the absence of angiotensin-converting enzyme inhibition. The degradation half-life of substance P correlated inversely with dipeptidyl peptidase IV antigen during angiotensin-converting enzyme inhibition. Environmental or genetic factors that reduce dipeptidyl peptidase IV activity may predispose individuals to angioedema.
authors.affiliation: Department of Medicine, Vanderbilt University Medical School, Nashville, TN, USA.
authors.forename: James Brian
authors.initials: JB
authors.lastname: Byrd
authors.forename: Karine
authors.initials: K
authors.lastname: Touzin
authors.forename: Saba
authors.initials: S
authors.lastname: Sile
authors.forename: James V
authors.initials: JV
authors.lastname: Gainer
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.forename: John
authors.initials: J
authors.lastname: Nadeau
authors.forename: Albert
authors.initials: A
authors.lastname: Adam
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000799:Angioedema / Q000139:chemically induced* / Q000201:enzymology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000941:Antigens / Q000276:immunology; D001920:Bradykinin / Q000378:metabolism; D016022:Case-Control Studies; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D013373:Substance P / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000941:Antigens; D013373:Substance P; D018819:Dipeptidyl Peptidase 4; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin