MiRNA Expression is Associated with Clinical Variables Related to Vascular Remodeling in the Kidney and the Brain in Type 2 Diabetes Mellitus Patients

Endocr Res. 2020 Feb-May;45(2):119-130. doi: 10.1080/07435800.2019.1690505. Epub 2019 Nov 14.

Abstract

Background: The association of vascular remodeling in the kidney and the brain with a particular microRNAs (miRNA) profile is not well studied.Methods: Seventy-six patients with Type 2 diabetes and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio (UACR), biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. MiRNA were quantified in blood and urine by a real-time PCR System. Cerebrovascular ultrasound measurements were performed in the carotid and middle cerebral arteries.Results: MiRNA21 and miRNA124 correlated positively with nephrin, podocalyxin, synaptopodin, urinary N-acetyl-D-glucosaminidase (NAG), urinary kidney-injury molecule-1 (KIM-1), UACR, and negatively with eGFR; miRNA125a, 126, 146a, 192 correlated negatively with nephrin, podocalyxin, synaptopodin, urinary NAG, urinary KIM-1, UACR, and directly with eGFR. Plasma miRNA-21 and miRNA192 correlated directly with cerebral hemodynamics parameters of atherosclerosis and arteriosclerosis. MiRNA-124, 125a, 126, 146a showed negative correlations with the same parameters.Conclusions: In Type 2 diabetes patients there is an association of vascular remodeling in the brain and the kidney with a specific miRNAs pattern. Cerebrovascular changes occur even in normoalbuminuric patients, with 'high-to-normal' levels of podocyte injury and PT dysfunction biomarkers. These phenomena may be explained by the variability of miRNA expression within the two organs in early DKD.

Keywords: Brain; diabetes mellitus; kidney; miRNA; vascular remodeling.

MeSH terms

  • Adult
  • Cerebrovascular Disorders / blood
  • Cerebrovascular Disorders / etiology
  • Cerebrovascular Disorders / metabolism*
  • Cerebrovascular Disorders / urine
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / urine
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / metabolism*
  • Diabetic Angiopathies / urine
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / urine
  • Female
  • Humans
  • Kidney Tubules / physiopathology
  • Male
  • MicroRNAs / blood
  • MicroRNAs / metabolism*
  • MicroRNAs / urine
  • Middle Aged
  • Podocytes / pathology
  • Vascular Remodeling / physiology*

Substances

  • MicroRNAs