TY - JOUR
T1 - Circulating MicroRNAs associate with diabetic nephropathy and systemic microvascular damage and normalize after simultaneous pancreas-kidney transplantation
AU - Bijkerk, R.
AU - Duijs, J. M.G.J.
AU - Khairoun, M.
AU - Ter Horst, C. J.H.
AU - Van Der Pol, P.
AU - Mallat, M. J.
AU - Rotmans, J. I.
AU - De Vries, A. P.J.
AU - De Koning, E. J.
AU - De Fijter, J. W.
AU - Rabelink, T. J.
AU - Van Zonneveld, A. J.
AU - Reinders, M. E.J.
N1 - Publisher Copyright:
© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
PY - 2015/4
Y1 - 2015/4
N2 - Because microvascular disease is one of the most important drivers of diabetic complications, early monitoring of microvascular integrity may be of clinical value. By assessing profiles of circulating microRNAs (miRNAs), known regulators of microvascular pathophysiology, in healthy controls and diabetic nephropathy (DN) patients before and after simultaneous pancreas-kidney transplantation (SPK), we aimed to identify differentially expressed miRNAs that associate with microvascular impairment. Following a pilot study, we selected 13 candidate miRNAs and determined their circulating levels in DN (n=21), SPK-patients (n=37), healthy controls (n=19), type 1 diabetes mellitus patients (n=15) and DN patients with a kidney transplant (n=15). For validation of selected miRNAs, 14 DN patients were studied longitudinally up to 12 months after SPK. We demonstrated a direct association of miR-25, -27a, -126, -130b, -132, -152, -181a, -223, -320, -326, -340, -574-3p and -660 with DN. Of those, miR-25, -27a, -130b, -132, -152, -320, -326, -340, -574-3p and -660 normalized after SPK. Importantly, circulating levels of some of these miRNAs tightly associate with microvascular impairment as they relate to aberrant capillary tortuosity, angiopoietin-2/angiopoietin-1 ratios, circulating levels of soluble-thrombomodulin and insulin-like growth factor. Taken together, circulating miRNA profiles associate with DN and systemic microvascular damage, and might serve to identify individuals at risk of experiencing microvascular complications, as well as give insight into underlying pathologies. Selected circulating microRNAs correlate with diabetic nephropathy and systemic microvascular damage, and normalize after simultaneous pancreas-kidney transplantation, providing novel opportunities for the identification of patients at risk for microvascular complications and pathways involved in disease progression.
AB - Because microvascular disease is one of the most important drivers of diabetic complications, early monitoring of microvascular integrity may be of clinical value. By assessing profiles of circulating microRNAs (miRNAs), known regulators of microvascular pathophysiology, in healthy controls and diabetic nephropathy (DN) patients before and after simultaneous pancreas-kidney transplantation (SPK), we aimed to identify differentially expressed miRNAs that associate with microvascular impairment. Following a pilot study, we selected 13 candidate miRNAs and determined their circulating levels in DN (n=21), SPK-patients (n=37), healthy controls (n=19), type 1 diabetes mellitus patients (n=15) and DN patients with a kidney transplant (n=15). For validation of selected miRNAs, 14 DN patients were studied longitudinally up to 12 months after SPK. We demonstrated a direct association of miR-25, -27a, -126, -130b, -132, -152, -181a, -223, -320, -326, -340, -574-3p and -660 with DN. Of those, miR-25, -27a, -130b, -132, -152, -320, -326, -340, -574-3p and -660 normalized after SPK. Importantly, circulating levels of some of these miRNAs tightly associate with microvascular impairment as they relate to aberrant capillary tortuosity, angiopoietin-2/angiopoietin-1 ratios, circulating levels of soluble-thrombomodulin and insulin-like growth factor. Taken together, circulating miRNA profiles associate with DN and systemic microvascular damage, and might serve to identify individuals at risk of experiencing microvascular complications, as well as give insight into underlying pathologies. Selected circulating microRNAs correlate with diabetic nephropathy and systemic microvascular damage, and normalize after simultaneous pancreas-kidney transplantation, providing novel opportunities for the identification of patients at risk for microvascular complications and pathways involved in disease progression.
UR - http://www.scopus.com/inward/record.url?scp=84925240349&partnerID=8YFLogxK
U2 - 10.1111/ajt.13072
DO - 10.1111/ajt.13072
M3 - Article
C2 - 25716422
AN - SCOPUS:84925240349
SN - 1600-6135
VL - 15
SP - 1081
EP - 1090
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 4
ER -
