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Abstract: TH-PO933

Angiotensin II Receptor Blocker (ARB) Alters the MicroRNA Profile of Extracellular Vesicles in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Kim, Hyoshik, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Republic of Korea, Seoul, Korea (the Republic of)
  • Kim, Yon hee, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Republic of Korea, Seoul, Korea (the Republic of)
  • Noh, Hyunjin, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Republic of Korea, Seoul, Korea (the Republic of)
  • Park, Moo Yong, Soonchunhyang University Hospital, Bucheon, Korea (the Republic of)
  • Kwon, Soon hyo, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, Seoul, Republic of Korea, Seoul, Korea (the Republic of)
Background

The renin-angiotensin system (RAS) is a major target of diabetes nephrapthy therapy. Angiotensin II receptor blockers (ARBs) decrease proteinuria and mortality associated with diabetes nephropathy. Extracellular vesicles (EVs) contain miRNAs that play a role in cell-to-cell communication and are biomarkers of disease. Whether ARBs modulate miRNAs in EVs is not known.

Methods

We prospectively enrolled 6 ARB naïve patients (male=4, female=2) with diabetic nephropathy and hypertension along with age-sex matched healthy volunteers (HVs). After collecting baseline samples, an ARB (losartan 50 mg) was added to the patients’ drug regimens. Serum EV microRNAs were profiled using RNA sequencing at baseline and 3 months after initiation of ARB therapy.

Results

RNA sequencing identified 130 miRNAs in the EVs from HVs and patients. ARB therapy decreased the expression of 5 miRNAs (miR-328-3p, miR-199a-5p, hsa-miR-16-5p, miR-1277-3p and miR-4284) in the EVs from patients. Expression of 3 miRNAs (miR-660-5p, miR-20b-5p and miR-143-3p) was increased after ARB therapy. Biological analysis identified the predicted involved pathways of the decreased miRNAs after ARB treatment (table 1).

Conclusion

Our study demonstrates that ARBs affect the expression of miRNAs in EVs from hypertensive patients. The change in expression of miRNAs in EVs due to ARB therapy is a novel aspect of the RAS. Further study is needed to identify the role of these miRNAs in diabetes.

The predicitve pathway of angiotensin receptor blocker responsive miRNAs
PathwayNumber of genesp-value
Pathway in cancer660.000162
Ribosome biogenesis in eukaryotes200.000849
Prostate cancer250.00037
Cell cycle310.000414
Chronic myeloid leukemia220.000414
Small cell lung cancer230.000419
RNA transport310.000419
HTLV-1 infection420.000703
Pancreatic cancer200.000951
Focal adhesion 400.0031