Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes: pooled analysis of three cohort studies

Cardiovascular Diabetology

Original Investigation

John H. Fuller¹  Casper G. Schalkwijk²  Coen D. A. Stehouwer²  Lian Engelen³  Stijn A. Peeters⁴  Jacqueline Buijs⁵  Hans-Henrik Parving⁶  Nish Chaturvedi⁷  Simone Theilade⁸  Anders Jorsal⁹  Lise Tarnow^1,10  Peter Rossing^1,11 

[1] Department of Epidemiology and Public Health, University College London, London, UK;Department of Internal Medicine, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands;CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands;Department of Internal Medicine, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands;Centraal Bureau voor de Statistiek, Heerlen, The Netherlands;Department of Internal Medicine, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands;Department of Internal Medicine, Zuyderland hospital, Heerlen, The Netherlands;Department of Internal Medicine, Zuyderland hospital, Heerlen, The Netherlands;Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;Institute of Cardiovascular Sciences, University College London, London, UK;Steno Diabetes Center Copenhagen, Gentofte, Denmark;Steno Diabetes Center Copenhagen, Gentofte, Denmark;Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark;Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark;Steno Diabetes Center Copenhagen, Gentofte, Denmark;Faculty of Health, Aarhus University, Aarhus, Denmark;Steno Diabetes Center Copenhagen, Gentofte, Denmark;University of Copenhagen, Copenhagen, Denmark;

关键词: Type 1 diabetes;    Matrix metalloproteinase;    Tissue inhibitor of metalloproteinase;    Pulse pressure;    Arterial stiffness;    Carotid-femoral pulse wave velocity;   

DOI  :  10.1186/s12933-017-0620-9

 received in 2017-07-20, accepted in 2017-10-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAltered regulation of extracellular matrix (ECM) composition by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) may contribute to arterial stiffening. We investigated associations between circulating MMP-1, -2, -3, -9, -10 and TIMP-1, and carotid-femoral pulse wave velocity (cfPWV) and pulse pressure (PP), as markers of arterial stiffness in type 1 diabetic patients.MethodsIndividuals with type 1 diabetes from three different cohorts were included in this study: EURODIAB Prospective Complications study (n = 509), LEACE (n = 370) and PROFIL (n = 638). Linear regression analyses were used to investigate cross-sectional associations between circulating levels of MMP-1, -2, -3, -9, -10, and TIMP-1 and cfPWV (n = 614) as well as office PP (n = 1517). Data on 24-h brachial and 24-h central PP were available in 638 individuals from PROFIL. Analyses were adjusted for age, sex, duration of diabetes, HbA1c, mean arterial pressure (MAP), and eGFR, and additionally for other cardiovascular risk factors and presence of vascular complications.ResultsAfter adjustment for potential confounders and presence of vascular complications, circulating MMP-3 was associated with cfPWV [β per 1 SD higher lnMMP3 0.29 m/s (0.02; 0.55)]. In addition, brachial and central 24-h PP measurements in PROFIL were significantly associated with MMP-2 [(1.40 (0.47:2.33) and 1.43 (0.63:2.23)]. Pooled data analysis showed significant associations of circulating levels of MMP-1 and MMP-2 with office PP [β per 1 SD higher lnMMP-1 and lnMMP-2 = − 0.83 mmHg (95% CI − 1.50; − 0.16) and = 1.33 mmHg (0.55; 2.10), respectively].ConclusionsMMPs-1, -2, and -3 are independently associated with markers of arterial stiffening in patients with type 1 diabetes and may become therapeutic targets.

【 授权许可】

CC BY   
© The Author(s) 2017

【 图 表 】

Fig. 3