posted on 2021-02-22, 17:40authored byAndrzej S Januszewski, Chris J Watson, Vikki O’Neill, Kenneth McDonald, Mark Ledwidge, Tracy RobsonTracy Robson, Alicia J Jenkins, Anthony C Keech, Lana McClements
Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). As disturbed angiogenesis and endothelial dysfunction are strongly implicated in T2D and CVD, we aimed to investigate the association between a novel anti-angiogenic protein, FK506-binding protein like (FKBPL), and these diseases. Plasma FKBPL was quantified by ELISA cross-sectionally in 353 adults, consisting of 234 T2D and 119 non-diabetic subjects with/without CVD, matched for age, BMI and gender. FKBPL levels were higher in T2D (adjusted mean: 2.03 ng/ml ± 0.90 SD) vs. non-diabetic subjects (adjusted mean: 1.79 ng/ml ± 0.89 SD, p = 0.02), but only after adjustment for CVD status. In T2D, FKBPL was negatively correlated with fasting blood glucose, HbA1c and diastolic blood pressure (DBP), and positively correlated with age, known diabetes duration, waist/hip ratio, urinary albumin/creatinine ratio (ACR) and fasting C-peptide. FKBPL plasma concentrations were increased in the presence of CVD, but only in the non-diabetic group (CVD: 2.02 ng/ml ± 0.75 SD vs. no CVD: 1.68 ng/ml ± 0.79 SD, p = 0.02). In non-diabetic subjects, FKBPL was positively correlated with an established biomarker for CVD, B-type Natriuretic Peptide (BNP), and echocardiographic parameters of diastolic dysfunction. FKBPL was a determinant of CVD in the non-diabetic group in addition to age, gender, total-cholesterol and systolic blood pressure (SBP). FKBPL may be a useful anti-angiogenic biomarker in CVD in the absence of diabetes and could represent a novel CVD mechanism..
Funding
Faculty Collaboration Seed funding, Faculty of Medicine, Health, Life Sciences, Queen’s University Belfast, Northern Ireland, United Kingdom
NHMRC Program grant to the NHMRC Clinical Trials Centre, and NHMRC Fellowships.
Health Research Board of Ireland, Grant number CSA-2012-36
History
Data Availability Statement
Supplementary material available at https://doi.org/10.1038/s41598-020-78676-6
Comments
The original article is available at https://www.nature.com/
Published Citation
Januszewski AS, Watson CJ, O'Neill V, McDonald K, Ledwidge M, Robson T, Jenkins AJ, Keech AC, McClements L. FKBPL is associated with metabolic parameters and is a novel determinant of cardiovascular disease. Scientific Reports. 2020;10(1):21655.