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Proteomic profiling of endothelium-dependent vasodilation
Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.ORCID-id: 0000-0002-6933-4637
2019 (engelsk)Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, nr 1, s. 216-222Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

OBJECTIVE: As endothelial dysfunction is an early event in atherosclerosis formation, we investigated if proteins previously related to cardiovascular disease also were related to endothelial function using a novel targeted proteomics approach.

METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 850-970, all aged 70 years), endothelium-dependent vasodilation (EDV) in the forearm was assessed by intra-arterial infusion of acetylcholine. Flow-mediated vasodilation (FMD) was investigated in the brachial artery by ultrasound. The same investigations were carried out in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 375-461, all aged 50 years). After strict quality control, 84 cardiovascular-related proteins measured by the proximity extension assay were studied in relation to EDV and FMD in PIVUS (discovery sample) and POEM (validation sample).

RESULTS: Of the 15 proteins being significantly related to EDV in PIVUS (false discovery rate <0.025), seven could be replicated in POEM at nominal significance and same effect direction when adjusted for sex and storage time. Of those, only cathepsin D remained significant following further adjustment for traditional cardiovascular risk factors (beta, -0.08; 95% confidence interval, -0.16, -0.01; P = 0.033; change in ln-transformed EDV per 1-SD increase in protein level). No protein was significantly related to FMD.

CONCLUSION: Using a discovery/validation approach in two samples, our results indicate an inverse association between plasma cathepsin D levels and endothelial-dependent vasodilation.

sted, utgiver, år, opplag, sider
2019. Vol. 37, nr 1, s. 216-222
HSV kategori
Forskningsprogram
Forskningsprofiler 2009-2020, Hälsa och välfärd
Identifikatorer
URN: urn:nbn:se:du-28816DOI: 10.1097/HJH.0000000000001863ISI: 000467336300031PubMedID: 30339551Scopus ID: 2-s2.0-85057537816OAI: oai:DiVA.org:du-28816DiVA, id: diva2:1257938
Tilgjengelig fra: 2018-10-23 Laget: 2018-10-23 Sist oppdatert: 2021-11-12bibliografisk kontrollert

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