ECE2018 Poster Presentations: Diabetes, Obesity and Metabolism Diabetes complications (72 abstracts)
Levels of scerostostin in serum and femoral vascular tissue and its relationship with atherosclerosis and cardiovascular mortality in patients with and without type 2 diabetes
Beatriz García-Fontana 1, , Cristina Novo-Rodríguez 1 , Francisco Andújar-Vera 1 , Cristina García-Fontana 1 , Sheila González-Salvatierra 1, , Teresa Márquez-Hernández 1, , Silvia Lozano-Alonso 4 , Sonia Morales-Santana 5 , Pedro Rozas-Moreno 6 , Antonia García-Martín 1, , Francisco O’valle-Ravassa 7 , Juan De Dios Luna-Del Castillo 8 & Manuel Muñoz-Torres 1,
1Endocrinology and Nutrition Unit, Hospital Universitario Campus de la Salud, Instituto de Investigación Biosanitaria de Granada (Ibs.GRANADA), Granada, Spain; 2CIBERFES. Instituto de Salud Carlos III, Madrid, Spain; 3Department of Medicine, University of Granada, Granada, Spain; 4Service of Angiology and Vascular Surgery, Universitario Campus de la Salud, Granada, Spain; 5Proteomic Research Service, Fundación para la Investigación Biosanitaria de Andalucía Oriental-Alejandro Otero, Instituto de Investigación Biosanitaria de Granada (Ibs.GRANADA), Granada, Spain; 6Endocrinology Division, Hospital General de Ciudad Real, Granada, Spain; 7Department of Pathological Anatomy, University of Granada, Granada, Spain; 8Department of Biostatistical, University of Granada, Granada, Spain.
Introduction: Sclerostin is a glycoprotein expressed mainly by osteocytes, which acts as inhibitor of bone formation. However, several studies have shown an increase in serum levels of sclerostin in subjects with type 2 diabetes (T2D) and cardiovascular disease (CVD) suggesting an additional role of this protein at the vascular level. The hypothesis that sclerostin could be expressed by vascular smooth muscle cells (VSMCs) under calcifying conditions could justify this elevation. However, there are few data at the tissue level.
Objectives: Determination of serum sclerostin levels in non-diabetic and T2D subjects with CVD and a at the transcriptional and immunohistochemical levels in femoral vascular tissue of patients with DM2 with atherosclerosis and non-atherosclerotic vascular tissue from healthy controls. Evaluation of the relationship between circulating sclerostin levels and cardiovascular mortality in subjects with and without T2D.
Material and methods: Serum sclerostin levels were determined in 75 T2D subjects with and without CVD and in 55 non-diabetic controls by commercial ELISA kit (Biomedica). Sclerostin expression was determined by RT-qPCR from 400 ng of total RNA from 45 sections of atherosclerotic femoral arterial tissue from subjects with T2D as well as from a healthy control. The gene expression was normalized according to the expression of two constitutive genes (GAPDH and ubiquitin). Immunohistochemical detection of sclerostin was performed on sections of paraffined vascular tissue using 1:50 antiesclerostin-specific antibody (Sigma Aldrich) and chromogenic detection. The relationship between sclerostin and cardiovascular mortality was assessed by a competitive risk analysis (Fine & Gray) after the 7-year follow-up of the cohort of diabetic and non-diabetic subjects with and without CVD.
Results: Serum sclerostin levels were significantly higher in T2D subjects with CVD compared to controls (58.29±26.36 vs 39.27±12.71 pmol/l, P<0.001). Increased expression of sclerostin at the transcriptional and immunohistochemical level was observed in atherosclerotic femoral artery of T2D patients compared with the femoral artery of healthy control. Serum sclerostin levels were independently associated with cardiovascular mortality (P=0.008).
Conclusions: The increase in serum sclerostin associated with CVD in T2D could be associated with an increased expression of this protein by vascular tissue. This suggests the involvement of sclerostin in the atherosclerotic process. In addition, high levels of sclerostin are associated with increased cardiovascular mortality, and it could act as new biomarker of cardiovascular mortality risk.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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