distinct kinin-induced functions are altered in circulating cells of young type 1 diabetic patients不同kinin-induced循环细胞功能改变的年轻的1型糖尿病患者.pdfVIP

Distinct Kinin-Induced Functions Are Altered in Circulating Cells of Young Type 1 Diabetic Patients ¨ 1 2 2 2 1 Nicolle Krankel *, Stephen Paul Armstrong , Craig Alexander McArdle , Colin Dayan , Paolo Madeddu 1 Experimental Cardiovascular Medicine, University of Bristol, Bristol, United Kingdom, 2 Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, Bristol, United Kingdom Abstract Aims/Hypothesis: We aimed to understand early alterations in kinin-mediated migration of circulating angio-supportive cells and dysfunction of kinin-sensitive cells in type-1 diabetic (T1D) patients before the onset of cardiovascular disease. Methods: Total mononuclear cells (MNC) were isolated from peripheral blood of 28 T1D patients free from cardiovascular complications except mild background retinopathy (age: 34.8 61.6 years, HbA1C: 7.960.2%) and 28 age- and sex-matched non-diabetic controls (H). We tested expression of kinin receptors by flow cytometry and migratory capacity of circulating monocytes and progenitor cells towards bradykinin (BK) in transwell migration assays. MNC migrating towards BK (BKmig) were assessed for capacity to support endothelial cell function in a matrigel assay, as well as generation of nitric oxide (NO) and superoxide (O22*) by using the fluorescent probes diaminofluorescein and dihydroethidium. Results: CD14hiCD16neg, CD14hiCD16pos and CD14loCD16pos monocytes and circulating CD34pos progenitor cells did not differ between T1D and H subjects in their kinin receptor expression and migration towards BK. T1D BKmig failed to generate NO upon BK stimulation and supported endothelial cell network formation less efficiently than H BK