Moo Yong Park1, Sandra M Herrmann2, Ahmed Saad2, Robert Jay Widmer3, Hui Tang2, Xiang-Yang Zhu2, Amir Lerman3, Stephen C Textor2, Lilach O Lerman4. 1. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea. 2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. 3. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. 4. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
Abstract
BACKGROUND: MicroRNAs (miRs) are small non-coding RNAs that are important regulators of gene expression and have been implicated in atherosclerosis. Kidney injury distal to atherosclerotic renal artery stenosis (ARAS) is aggravated by atherosclerosis. Therefore, this study tested the hypothesis that renal miR expression would be altered in patients with ARAS. METHODS: Patients with essential hypertension (EH; n = 13) or ARAS (n = 13) underwent a 3-day protocol study under controlled conditions. For miR levels, blood samples were collected from EH and ARAS renal vein (RV) and inferior vena cava or peripheral vein of matched normotensive healthy volunteers (HV; n = 13) and patients with coronary atherosclerosis (CA; n = 11). Single-renal blood flow was measured in EH and ARAS using computer tomography to calculate renal gradients and release of miRs. RESULTS: Glomerular filtration rate (GFR) was lower in ARAS compared with the other groups. Systemic levels of most miRs were elevated in CA. RV miR levels were lower than systemic levels in both ARAS and EH. GFR-adjusted RV levels of miR-21, 155 and 210 were reduced only in ARAS patients compared with systemic levels in HV, although cross-kidney gradients were not different from EH. RV levels of miR-21, 126, 155 and 210 correlated with GFR. CONCLUSIONS: Levels of atherosclerosis-related miR-21, 126, 155 and 210 are decreased in the stenotic-kidney vein of ARAS compared with EH patients, likely due to decreased GFR. Yet, these miRs might be implicated in modulating renal injury in ARAS, and their RV level may be a marker reflecting their renal expression.
BACKGROUND: MicroRNAs (miRs) are small non-coding RNAs that are important regulators of gene expression and have been implicated in atherosclerosis. Kidney injury distal to atherosclerotic renal artery stenosis (ARAS) is aggravated by atherosclerosis. Therefore, this study tested the hypothesis that renal miR expression would be altered in patients with ARAS. METHODS:Patients with essential hypertension (EH; n = 13) or ARAS (n = 13) underwent a 3-day protocol study under controlled conditions. For miR levels, blood samples were collected from EH and ARAS renal vein (RV) and inferior vena cava or peripheral vein of matched normotensive healthy volunteers (HV; n = 13) and patients with coronary atherosclerosis (CA; n = 11). Single-renal blood flow was measured in EH and ARAS using computer tomography to calculate renal gradients and release of miRs. RESULTS: Glomerular filtration rate (GFR) was lower in ARAS compared with the other groups. Systemic levels of most miRs were elevated in CA. RV miR levels were lower than systemic levels in both ARAS and EH. GFR-adjusted RV levels of miR-21, 155 and 210 were reduced only in ARASpatients compared with systemic levels in HV, although cross-kidney gradients were not different from EH. RV levels of miR-21, 126, 155 and 210 correlated with GFR. CONCLUSIONS: Levels of atherosclerosis-related miR-21, 126, 155 and 210 are decreased in the stenotic-kidney vein of ARAS compared with EH patients, likely due to decreased GFR. Yet, these miRs might be implicated in modulating renal injury in ARAS, and their RV level may be a marker reflecting their renal expression.
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