Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema.
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.
Byrd
James Brian
JB
Department of Medicine, Vanderbilt University Medical School, Nashville, TN, USA.
Touzin
Karine
K
Sile
Saba
S
Gainer
James V
JV
Yu
Chang
C
Nadeau
John
J
Adam
Albert
A
Brown
Nancy J
NJ
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D000941:Antigens; D013373:Substance P; D018819:Dipeptidyl Peptidase 4; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin