Dipeptidyl peptidase 3, a marker of the antagonist pathway of the renin–angiotensin–aldosterone system in patients with heart failure

Boorsma, Eva M; Maaten, Jozine M. ter; Damman, Kevin; Veldhuisen, Dirk J. van; Dickstein, Kenneth; Anker, Stefan D.; Filippatos, Gerasimos; Lang, Chim C.; Metra, Marco; Santos, Karine; Voors, Adriaan A.

doi:10.1002/ejhf.2158

Cited by 9 publications

(13 citation statements)

References 23 publications

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“…Notably, we revealed here that lower circulating Dpp3 enzymatic levels are associated with a worse skeletal phenotype; conversely, in sepsis, cardiogenic shock, heart failure, and acute kidney injury the correlation goes in the opposite direction, with higher levels resulting in more severe disease and reduced survival rate [19][20][21][22][23][24][25]. In these conditions, angiotensin 2, the primary effector of the renin-angiotensin system (RAS), is recognized as the key substrate of Dpp3 activity and clinical evidence has been interpreted based on the modulation of the RAS by Dpp3, and the resulting impact on hemodynamics and on the physiology of the cardiovascular system.…”

Section: Discussionmentioning

confidence: 77%

Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women

et al. 2022

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The dipeptidyl peptidase 3 (Dpp3) is a ubiquitous zinc-dependent aminopeptidase, participating in the activation or degradation of signaling peptides and in the Keap1–Nrf2 antioxidant pathway. The absence of Dpp3 in the Dpp3 knockout mouse model causes increased osteoclast activity, altered osteogenic function, sustained oxidative stress in the bone tissue, and bone loss. We aimed to assess the association of Dpp3 activity with bone fragility in postmenopausal osteoporosis and the impact of denosumab on enzymatic activity. We conducted a two-phase study including 69 postmenopausal women with severe osteoporosis and 36 postmenopausal women without osteometabolic conditions, as controls (cross-sectional phase). Subjects with severe osteoporosis were assessed at baseline and 14 days after the first denosumab administration (prospective phase). The results showed significant reduction in serum Dpp3 activity (expressed as nmoles of formed product/mg proteins/min) in patients vs. controls (0.791 ± 0.232 vs. 1.195 ± 0.338; p < 0.001), and significant association with bone mass at the femoral neck (r = 0.28, p = 0.02) in patients prior to treatment. We found a negative correlation between C-terminal telopeptide (CTX) or N-terminal pro-peptide of type 1 procollagen (P1NP) levels and Dpp3 activity (respectively, r = −0.29, p = 0.012; and r = −0.2572, p = 0.033). Dpp3 activity did not change after denosumab injection. Our findings support a critical role played by Dpp3 in bone homeostasis as a potential bone protective factor. Additional clinical studies in larger cohorts might explore the implementation of Dpp3 assessment as a biomarker of bone health status.

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Section: Discussionmentioning

confidence: 77%

Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women

et al. 2022

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“…10 Higher levels of circulating dipeptidyl peptidase 3 (DPP3) were related with mortality in patients with cardiogenic shock and DPP3 inhibition can improve haemodynamics. 11,12 Boorsma et al 13 showed that high DPP3 levels are associated with higher renin and aldosterone concentrations and poorer outcomes.…”

Section: Biomarkersmentioning

confidence: 99%

June 2021 at a glance: focus on epidemiology, biomarkers and medical treatment

Tomasoni

Adamo

Metra

2021

European J of Heart Fail

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The epidemiology of heart failure (HF) is still unsettled, above all in European countries, because of marked differences in coding and management modalities. To date, most of our data came from analyses of dedicated studies and trials. 1,2 The Heart Failure Association (HFA) Atlas is a novel European data set, developed to provide a contemporary description of HF epidemiology and management. 3,4 The median incidence of HF was 3.2 [interquartile range (IQR) 2.66-4.17] cases per 1000 person-years; the median HF prevalence was 17.20 (IQR 14.30-21) cases per 1000 people and the median number of HF hospitalizations was 2671 (IQR 1771-4317) per million people, annually. A large heterogeneity among different countries both with respect to epidemiology and management was shown. 3 Diagnosis and prognosis Endomyocardial biopsyTreatment of cardiomyopathies and myocarditis remains challenging. [5][6][7] Indications to endomyocardial biopsy needed to be updated accordingly and this issue hosts a consensus document developed by HFA, HF Society of America and Japanese HF Society. 8 Evidence-based medical treatment is still underused in patients with HF and reduced ejection fraction. 23,24 In a HFA consensus document, Rosano et al. 25 identified nine patient profiles which may inform treatment choices. These profiles include patients with atrial fibrillation, low blood pressure, tachycardia, chronic kidney disease, hyperkalaemia, congestion, or pre-discharge status. A strategy of rapid sequencing of evidence-based treatment was also proposed to optimize medical treatment. 26

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“…Elevated cDPP3 is associated with therapy refractoriness in cardiogenic shock [2]. Recently, cDPP3 levels were determined in 2314 advanced heart failure (HF) patients of the BIOSTAT-CHF observational cohort, revealing an increase in the combined endpoint of all-cause mortality and HF hospitalizations in the highest quartile [3].…”

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confidence: 99%

“…Consecutive patients with advanced HFrEF and GDMT were enrolled prospectively from the HF outpatient clinic at the Medical University of Vienna between February 2016 and December 2017. Routine laboratory parameters including NT-proBNP and active plasma renin concentration (ARC), and additionally a set of other established HF neurohumoral biomarkers-norepinephrine (NE), growth differentiation factor 15 (GDF-15), copeptin, big endothelin 1 (big-ET-1) and plasma neprilysin (NEP) activity-were measured in plasma by specific immunoassays and a fluorokinetic assay as described earlier [3]. Bioactive adrenomedullin (bio-ADM) and pro-enkephalin-A 119-159 (PENK) were determined in serum samples by the sphingotest ® assay.…”

mentioning

confidence: 99%

“…Bioactive adrenomedullin (bio-ADM) and pro-enkephalin-A 119-159 (PENK) were determined in serum samples by the sphingotest ® assay. Blinded cDPP3 measurements in serum were organized by 4TEEN4 Pharmaceuti-cals GmbH (Hennigsdorf, Germany) using a luminometric immunoassay (DPP3-LIA) [3]. Because DPP3 is classified as a primary cytosolic enzyme and can be released from erythrocytes during hemolysis, hemolytic samples were excluded from the analysis.…”

mentioning

confidence: 99%

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