Decreased MicroRNA Is Involved in the Vascular Remodeling Abnormalities in Chronic Kidney Disease (CKD)

Xuening (Neal) Chen, Kraiwiporn Kiattisunthorn, Kalisha D. O'Neill, Xianming Chen, Ranjani Moorthi, Vincent H. Gattone, Matthew Allen, Sharon Moe

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Patients with CKD have abnormal vascular remodeling that is a risk factor for cardiovascular disease. MicroRNAs (miRNAs) control mRNA expression intracellularly and are secreted into the circulation; three miRNAs (miR-125b, miR-145 and miR-155) are known to alter vascular smooth muscle cell (VSMC) proliferation and differentiation. We measured these vascular miRNAs in blood from 90 patients with CKD and found decreased circulating levels with progressive loss of eGFR by multivariate analyses. Expression of these vascular miRNAs miR-125b, miR-145, and miR-155 was decreased in the thoracic aorta in CKD rats compared to normal rats, with concordant changes in target genes of RUNX2, angiotensin II type I receptor (AT1R), and myocardin. Furthermore, the expression of miR-155 was negatively correlated with the quantity of calcification in the aorta, a process known to be preceded by vascular de-differentiation in these animals. We then examined the mechanisms of miRNA regulation in primary VSMC and found decreased expression of miR-125b, 145, and 155 in VSMC from rats with CKD compared to normal littermates but no alteration in DROSHA or DICER, indicating that the low levels of expression is not due to altered intracellular processing. Finally, overexpression of miR-155 in VSMC from CKD rats inhibited AT1R expression and decreased cellular proliferation supporting a direct effect of miR-155 on VSMC. In conclusion, we have found ex vivo and in vitro evidence for decreased expression of these vascular miRNA in CKD, suggesting that alterations in miRNAs may lead to the synthetic state of VSMC found in CKD. The decreased levels in the circulation may reflect decreased vascular release but more studies are needed to confirm this relationship.

Original languageEnglish
Article numbere64558
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 22 2013

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kidney diseases
MicroRNAs
Chronic Renal Insufficiency
microRNA
blood vessels
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Blood Vessels
smooth muscle
myocytes
Rats
Cell Proliferation
rats
Angiotensin I
Angiotensin Receptors
aorta
Vascular Remodeling
Thoracic Aorta
cell proliferation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Decreased MicroRNA Is Involved in the Vascular Remodeling Abnormalities in Chronic Kidney Disease (CKD). / Chen, Xuening (Neal); Kiattisunthorn, Kraiwiporn; O'Neill, Kalisha D.; Chen, Xianming; Moorthi, Ranjani; Gattone, Vincent H.; Allen, Matthew; Moe, Sharon.

In: PLoS One, Vol. 8, No. 5, e64558, 22.05.2013.

Research output: Contribution to journalArticle

Chen, Xuening (Neal) ; Kiattisunthorn, Kraiwiporn ; O'Neill, Kalisha D. ; Chen, Xianming ; Moorthi, Ranjani ; Gattone, Vincent H. ; Allen, Matthew ; Moe, Sharon. / Decreased MicroRNA Is Involved in the Vascular Remodeling Abnormalities in Chronic Kidney Disease (CKD). In: PLoS One. 2013 ; Vol. 8, No. 5.
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