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Cited by 147Coagulation, Bradykinin, Polyphosphates, and AngioedemaRenin-Angiotensin System StudiesPeptidase Inhibition and Analysis

Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema

Open access
Byrd, James Brian, Touzin, Karine, Sile, Saba, Gainer, James V., Yu, Chang, Nadeau, John, Adam, Albert, Brown, Nancy J.·2008·Hypertension
DOI 10.1161/hypertensionaha.107.096552PMC PMC2749928
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Abstract

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. DPPIV activity and antigen were decreased in patients.

Integrity signals

Registry

Crossref · 10.1161/hypertensionaha.107.096552

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

12 of 36 cited sources checked · 9 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The frequency of decreased APP activity in the population (18%) exceeds the incidence of angioedema in ACEi-exposed patients.

    “In addition, the frequency of decreased APP activity in the population (18%) exceeds the incidence of angioedema in ACEi-exposed patients.16”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [16] 16. Cyr M, Lepage Y, Blais C Jr, Gervais N, Cugno M, Rouleau JL, Adam A. Bradykinin and des-Arg (9)-bradykinin metabolic pathways and kinetics of activation of human plasma. Am J Physiol Heart Circ Physiol 2001;281:H275-H283. [PubMed: 11406494] source

      The Results (p. 5) report APP activity in 116 healthy individuals, but do not give an 18% frequency of decreased activity. The discussion (p. 8) mentions ACE-inhibitor-associated angioedema without stating its incidence. Searches for the 18% figure and an angioedema incidence did not establish the claimed comparison. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
  • Premisecitation

    DPPIV-deficient Fisher 344 rats demonstrate increased susceptibility to ACEi-induced peritracheal edema through an NK1 receptor-dependent mechanism.

    “Likewise, we have observed recently that DPPIV-deficient Fisher 344 rats demonstrate increased susceptibility to ACEi-induced peritracheal edema through an NK 1 receptordependent mechanism.24”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [24] 24. Byrd JB, Shreevatsa A, Putlur P, Foretia D, McAlexander L, Sinha T, Does MD, Brown NJ. Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema. J Allergy Clin Immunol 2007;120:403-408. [PubMed: 17531305] source

      The Animals and Abstract sections identify DPPIV-deficient Fisher F344 rats and report greater captopril-induced peritracheal edema, attenuated by the neurokinin receptor antagonist spantide. The Discussion describes this as evidence for a neurokinin receptor-dependent mechanism, but the study does not establish that the effect specifically depends on NK1 receptors. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    Substance P contributes to the development of ACEi-associated angioedema in rodent models.

    “Although this study does not specifically address the mechanism underlying the association between decreased DPPIV activity and antigen and ACEi-associated angioedema, substance P contributes to the development of ACEi-associated angioedema in rodent models.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [9] 9. Emanueli C, Grady EF, Madeddu P, Figini M, Bunnett NW, Parisi D, Regoli D, Geppetti P. Acute ACE inhibition causes plasma extravasation in mice that is mediated by bradykinin and substance P. Hypertension 1998;31:1299-1304. [PubMed: 9622145] source
    • cites [10] 10. Sulpizio AC, Pullen MA, Edwards RM, Brooks DP. The effect of acute angiotensin-converting enzyme and neutral endopeptidase 24.11 inhibition on plasma extravasation in the rat. J Pharmacol Exp Ther 2004;309:1141-1147. [PubMed: 14769834] source
    • cites [24] 24. Byrd JB, Shreevatsa A, Putlur P, Foretia D, McAlexander L, Sinha T, Does MD, Brown NJ. Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema. J Allergy Clin Immunol 2007;120:403-408. [PubMed: 17531305] source
  • Findingown data

    Bradykinin half-life correlates inversely with ACE activity in the absence of ACEi.

    “Bradykinin half-life correlated inversely with ACE activity in the sera in the absence of ACEi (r=-0.535;P=0.002) and as well as with ACE activity in sera from subjects taking an ACEi (r=-0.259;P=0.047).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Among subjects taking an ACEi, DPPIV activity tends to be higher in diabetic subjects compared with nondiabetic subjects.

    “Among subjects taking an ACEi, DPPIV activity was lower in smokers compared with nonsmokers (27.1±8.0 versus 29.8±.6.6 nmol/mL per minute; P=0.04) and tended to be higher in diabetic subjects compared with nondiabetic subjects (30.6±7.1 versus 28.6±6.6 nmol/mL per minute; P=0.07).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 17
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Premisecitation

    APP activity and des-Arg9-bradykinin degradation are decreased in the sera of angioedema patients of European origin compared with control subjects.

    “Supporting this notion, APP activity and des-Arg 9 -bradykinin degradation are decreased in the sera of angioedema patients of European origin compared with control subjects.13,14”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [13] 13. Adam A, Cugno M, Molinaro G, Perez M, Lepage Y, Agostoni A. Aminopeptidase P in individuals with a history of angio-oedema on ACE inhibitors. Lancet 2002;359:2088-2089. [PubMed: 12086766] source
    • cites [14] 14. Molinaro G, Cugno M, Perez M, Lepage Y, Gervais N, Agostoni A, Adam A. Angiotensin-converting enzyme inhibitor-associated angioedema is characterized by a slower degradation of des-arginine (9)-bradykinin. J Pharmacol Exp Ther 2002;303:232-237. [PubMed: 12235256] source

      The Discussion reports slower des-Arg9-bradykinin degradation in angioedema patients than controls and cites prior observations of decreased APP activity in the same patients. However, the Blood Samples section says this study tested plasma, not serum, and the Patients section describes participants as white without establishing European origin. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Studies report an increased incidence of nasopharyngitis in subjects randomly assigned to DPPIV inhibitor.

    “However, studies report an increased incidence of nasopharyngitis in subjects randomly assigned to DPPIV inhibitor 35,38,40 ; in 1 study, 1 of 175 sitagliptin-treated subjects was hospitalized for angioedema.41”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [35] 35. Ahren B, Simonsson E, Larsson H, Landin-Olsson M, Torgeirsson H, Jansson PA, Sandqvist M, Bavenholm P, Efendic S, Eriksson JW, Dickinson S, Holmes D. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care 2002;25:869-875. [PubMed: 11978683] source
    • cites [38] 38. Pi-Sunyer FX, Schweizer A, Mills D, Dejager S. Efficacy and tolerability of vildagliptin monotherapy in drug-naive patients with type 2 diabetes. Diabetes Res Clin Pract 2007;76:132-138. [PubMed: 17223217] source
    • cites [40] 40. Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006;29:2638-2643. [PubMed: 17130197] source

  • May combine two claims.

    Premisecitation

    Published trials have either not included subjects taking ACEi or have not commented on the inclusion of subjects exposed to ACEis.

    “Published trials have either not included subjects taking ACEi or have not commented on the inclusion of subjects exposed to ACEis.[35][36][37][38][39]”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [35] 35. Ahren B, Simonsson E, Larsson H, Landin-Olsson M, Torgeirsson H, Jansson PA, Sandqvist M, Bavenholm P, Efendic S, Eriksson JW, Dickinson S, Holmes D. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care 2002;25:869-875. [PubMed: 11978683] source
    • cites [36] 36. Ahren B, Gomis R, Standl E, Mills D, Schweizer A. Twelve-and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 2004;27:2874-2880. [PubMed: 15562200] source
    • cites [37] 37. Mari A, Sallas WM, He YL, Watson C, Ligueros-Saylan M, Dunning BE, Deacon CF, Holst JJ, Foley JE. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 2005;90:4888-4894. [PubMed: 15886245] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Clinical studies of DPPIV inhibitors indicate that this class of drugs improves glycemic control in patients with type 2 diabetes mellitus.

    “Clinical studies of DPPIV inhibitors indicate that this class of drugs improves glycemic control in patients with type 2 diabetes mellitus.[35][36][37]”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [35] 35. Ahren B, Simonsson E, Larsson H, Landin-Olsson M, Torgeirsson H, Jansson PA, Sandqvist M, Bavenholm P, Efendic S, Eriksson JW, Dickinson S, Holmes D. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care 2002;25:869-875. [PubMed: 11978683] source
    • cites [36] 36. Ahren B, Gomis R, Standl E, Mills D, Schweizer A. Twelve-and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 2004;27:2874-2880. [PubMed: 15562200] source
    • cites [37] 37. Mari A, Sallas WM, He YL, Watson C, Ligueros-Saylan M, Dunning BE, Deacon CF, Holst JJ, Foley JE. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 2005;90:4888-4894. [PubMed: 15886245] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DPPIV activity has been associated with increased glucose concentrations in diabetic subjects.

    “Likewise, DPPIV activity has been associated with increased glucose concentrations in diabetic subjects.32”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [32] 32. Mannucci E, Pala L, Ciani S, Bardini G, Pezzatini A, Sposato I, Cremasco F, Ognibene A, Rotella CM. Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus. Diabetologia 2005;48:1168-1172. [PubMed: 15864535] source

  • May combine two claims.

    Findingown data

    DPPIV antigen is decreased in sera from cases collected during ACE inhibition but not in the absence of ACE inhibition.

    “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±163.2ng/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.”
    • Also stated in: § Results · plain
      “When analyzed separately in subjects currently taking an ACEi and those no longer taking an ACEi, DPPIV activity and antigen were lower in case subjects than in control subjects only among subjects exposed to ACEi at the time of blood collection (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    DPPIV activity is decreased in sera from cases collected during ACE inhibition but not in the absence of ACE inhibition.

    “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±163.2ng/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.”
    • Also stated in: § Results · plain
      “When analyzed separately in subjects currently taking an ACEi and those no longer taking an ACEi, DPPIV activity and antigen were lower in case subjects than in control subjects only among subjects exposed to ACEi at the time of blood collection (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Des-Arg9-bradykinin half-life correlates inversely with APP activity in the absence of ACEi but not during ACE inhibition.

    “Des-Arg 9 -bradykinin half-life correlated inversely with APP activity (r=-0.445;P=0.01) in the absence of ACEi but not during ACE inhibition.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There is no difference in ACE activity, APP activity, APN activity, bradykinin degradation half-life, or des-Arg9-bradykinin degradation half-life between case and control subjects either in the presence or absence of ACE inhibition.

    “However, there was no difference in ACE activity, APP activity, APN activity, bradykinin degradation half-life, or des-Arg 9 -bradykinin degradation half-life between case and control subjects either in the presence or absence of ACE inhibition.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among both case and control subjects, ACE activity is significantly lower, and the half-lives of degradation of bradykinin and des-Arg9-bradykinin are significantly prolonged, in individuals taking an ACEi compared with those not taking an ACEi.

    “Among both case and control subjects, ACE activity was significantly lower, and the half-lives of degradation of bradykinin and its active metabolite des-Arg 9 -bradykinin were significantly prolonged in individuals taking an ACEi compared with those not taking an ACEi.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The degradation half-life of substance P correlated with DPPIV antigen only during ACE inhibition; however, the majority of individuals with ACEi-associated angioedema were no longer taking an ACEi at the time that their blood was collected.

    “The degradation half-life of substance P correlated with DPPIV antigen only during ACE inhibition; however, the majority of individuals with ACEi-associated angioedema were no longer taking an ACEi at the time that their blood was collected.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Unexpectedly, there is no difference in APP activity or des-Arg9-bradykinin concentrations between case and control subjects.

    “Unexpectedly, we found no difference in APP activity or des-Arg 9 -bradykinin concentrations between case and control subjects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    We did not detect an effect of either race or gender on enzyme activity or peptide degradation.

    “Nevertheless, we did not detect an effect of either race or gender on enzyme activity or peptide degradation.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Analyses were performed after stratification for ACEi use at the time of blood collection to account for different proportions of case and control subjects exposed to ACEi.

    “To account for the different proportions of case and control subjects exposed to ACEi at the time of blood collection, analyses were performed after stratification for ACEi use at the time of blood collection, except as indicated otherwise in the text.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The study was approved by the Vanderbilt University Institutional Review Board, and all subjects provided written informed consent.

    “The study was approved by the Vanderbilt University Institutional Review Board, and all of the subjects provided written informed consent.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    It is plausible that either decreased APP activity or decreased DPPIV activity could result in the common phenotype of ACEi-associated angioedema.

    “Moreover, given that bradykinin stimulates the release of substance P, 33 it is plausible that either decreased APP activity, leading to decreased inactivation of bradykinin and des-Arg 9 -bradykinin with consequent stimulation of substance P release, or decreased DPPIV activity, leading to decreased inactivation of substance P, could result in the common phenotype of ACEiassociated angioedema.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] 33. Kopp UC, Farley DM, Smith LA. Bradykinin-mediated activation of renal sensory neurons due to prostaglandin-dependent release of substance P. Am J Physiol 1997;272:R2009-R2016. [PubMed: 9227622] source

  • May combine two claims.

    Premisecitation

    Bradykinin and substance P, substrates of ACE, increase vascular permeability and cause tissue edema in animals.

    “Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals.”
    • Also stated in: § Abstract · plain
      “Bradykinin and substance P are 2 substrates of ACE that produce tracheal edema in animals.9,10”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [9] 9. Emanueli C, Grady EF, Madeddu P, Figini M, Bunnett NW, Parisi D, Regoli D, Geppetti P. Acute ACE inhibition causes plasma extravasation in mice that is mediated by bradykinin and substance P. Hypertension 1998;31:1299-1304. [PubMed: 9622145] source
    • cites [10] 10. Sulpizio AC, Pullen MA, Edwards RM, Brooks DP. The effect of acute angiotensin-converting enzyme and neutral endopeptidase 24.11 inhibition on plasma extravasation in the rat. J Pharmacol Exp Ther 2004;309:1141-1147. [PubMed: 14769834] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The regulation of DPPIV expression seems to be tissue specific.

    “The regulation of DPPIV expression seems to be tissue specific, 28,29 and soluble antigen concentrations may reflect not only expression but also cleavage from the cell surface.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] 28. Abbott CA, Baker E, Sutherland GR, McCaughan GW. Genomic organization, exact localization, and tissue expression of the human CD26 (dipeptidyl peptidase IV) gene. Immunogenetics 1994;40:331-338. [PubMed: 7927537] source
    • cites [29] 29. Bohm SK, Gum JR Jr, Erickson RH, Hicks JW, Kim YS. Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter. Biochem J 1995;311:835-843. [PubMed: 7487939] source

  • May combine two claims.

    Study design and conductreasoning

    The study has limitations of small sample size and serum measurements.

    “This suggests the need to identify additional mechanisms whereby decreased DPPIV activity and antigen concentrations associate with ACEi-associated angioedema but also highlights the limitations of small sample size and serum measurements.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The ex vivo degradation of substance P may not reflect its local in vivo metabolism.

    “Similarly, the ex vivo degradation of substance P may not reflect its local in vivo metabolism.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    At least 1 previous study reported lower DPPIV activity in bronchial alveolar lavage fluid from smokers compared with fluid from non-smokers.

    “At least 1 previous study reported lower DPPIV activity in bronchial alveolar lavage fluid from smokers compared with fluid from non-smokers.31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] 31. Van DV V, Naber BA, Van Hal PT, Overbeek SE, Hoogsteden HC, Versnel MA. Peptidase activities in serum and bronchoalveolar lavage fluid from allergic asthmatics-omparison with healthy non- smokers and smokers and effects of inhaled glucocorticoids. Clin Exp Allergy 1999;29:813-823. [PubMed: 10336599] source

  • May combine two claims.

    Premisecitation

    Bradykinin stimulates the release of substance P from sensory nerves, which causes increased vascular permeability by acting at the NK1 receptor.

    “In addition to increasing vascular permeability directly via its B 2 receptor, bradykinin stimulates the release of substance P from sensory nerves, which causes increased vascular permeability by acting at the NK 1 receptor.19”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] 19. Campos MM, Calixto JB. Neurokinin mediation of edema and inflammation. Neuropeptides 2000;34:314-322. [PubMed: 11049735] source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Des-Arg9-bradykinin acts as a proinflammatory agonist at the B1 receptor and is degraded primarily via APP.

    “Des-Arg 9 -bradykinin acts as a proinflammatory agonist at the B 1 receptor and is degraded primarily via APP.22”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] 22. Pesquero JB, Jubilut GN, Lindsey CJ, Paiva AC. Bradykinin metabolism pathway in the rat pulmonary circulation. J Hypertens 1992;10:1471-1478. [PubMed: 1363432] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Medical history, including the history of angioedema, was confirmed by a research nurse or physician using a detailed case report form.

    “Medical history, including the history of angioedema, was confirmed by a research nurse or physician using a detailed case report form.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The contrast with data from a largely European population may reflect differences in ethnicity or in concurrent ACEi use.

    “This contrasts with data from a largely European population 13 and may reflect differences in ethnicity or in concurrent ACEi use.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] 13. Adam A, Cugno M, Molinaro G, Perez M, Lepage Y, Agostoni A. Aminopeptidase P in individuals with a history of angio-oedema on ACE inhibitors. Lancet 2002;359:2088-2089. [PubMed: 12086766] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Serum DPPIV activity correlates with the T-cell membrane-bound antigen.

    “Although serum DPPIV activity correlates with the T-cell membrane-bound antigen, 26 membrane-bound DPPIV in connective tissue stroma has a 10-fold lower Michaelis constant than does soluble DPPIV.27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] 26. Elgun S, Keskinege A, Akan H, Karaca L. Serum dipeptidyl peptidase IV activity correlates with the T-cell CD26 antigen. Clin Chem Lab Med 1999;37:839-840. [PubMed: 10536934] source
26 of 26

  • The paper relies on this without support.

    The mechanism of ACEi-associated angioedema is unknown.

    “Although bradykinin has been implicated in the pathogenesis of hereditary forms of angioedema, 4 the mechanism of ACEi-associated angioedema is unknown.”

  • The paper relies on this without support.

    Serum DPPIV activity and antigen reflect the relevant tissue DPPIV activity in the pathogenesis of ACEi-associated angioedema.

    “In addition, we measured soluble DPPIV antigen and serum activity, but DPPIV is a cell-surface-associated peptidase.21”

  • The paper relies on this without support.

    Ex vivo degradation half-life of substance P reflects its local in vivo metabolism.

    “Similarly, the ex vivo degradation of substance P may not reflect its local in vivo metabolism.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Diabetic count in the serum subset exceeds the full-group count

    Minor

    The table lists 110 diabetic controls in the serum-available subset, but only 64 diabetic controls in the full group. The serum-available controls are a subset of the full group, so their diabetic count cannot be larger.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. 10.1161/hyp.31.6.1299 · DOI
  2. 10.1161/hyp.39.2.460 · DOI

Cited by

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Related

Authors
Byrd, J. B., Touzin, K., Sile, S., Gainer, J. V., Yu, C., Nadeau, J., Adam, A., & Brown, N. J.
Affiliations
United States Department of Veterans Affairs (US)
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2008-01
Volume
51
Issue
1
Pages
141-147
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.107.096552
PMC
PMC2749928
OpenAlex
W2065408836
Cited by
147
References
43
Citations by year
2026: 1 · 2025: 6 · 2024: 4 · 2023: 11 · 2022: 4 · 2021: 8 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 11 · 2016: 11 · 2015: 8 · 2014: 13 · 2013: 8 · 2012: 10
FWCI
4.07
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Deep Blue (University of Michigan) (submittedVersion)
  • University of Michigan Library
Funders
  • National Institutes of Health (5r01hl065193-12)
  • National Heart, Lung, and Blood Institute (T32HL076133, R01-HL076133, R01HL079184, R01-HL065193)
  • National Institute of General Medical Sciences (T32GM007569)
  • National Center for Research Resources (M01RR000095)
Topics
  • Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
Keywords
dipeptidyl peptidase IV, bradykinin degradation, aminopeptidase P, CD13, bradykinin B2 receptor, bradykinin B1 receptor
MeSH terms
Adult, Aged, Angioedema, Angiotensin-Converting Enzyme Inhibitors, Antigens, Bradykinin, Female, Humans, Hypertension, Peptidyl-Dipeptidase A, Male, Middle Aged, Substance P, Case-Control Studies, Dipeptidyl Peptidase 4, Genetic Predisposition to Disease

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