Endothelial dysfunction occurs prior to clinical evidence of polycystic kidney disease

Karen M. Peterson, Federico Franchi, Darrel L. Loeffler, Peter J. Psaltis, Peter C. Harris, Lilach O. Lerman, Amir Lerman, Martin Rodriguez-Porcel

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: Polycystic kidney disease (PKD), a monogenic disease with an autosomal dominant or an autosomal recessive form of inheritance (ARPKD), is the most common genetic cause of renal dysfunction and end-stage renal failure. In addition to the development of cysts, the autosomal form of PKD is associated with vascular endothelial dysfunction, a marker of vascular disease. Whether vascular endothelial dysfunction is also present in ARPKD, and its relationship with renal dysfunction remain to be determined. Methods: ARPKD rats (PCK model) and controls were studied at 6 and 10 weeks of age, and mean arterial pressure and renal function were measured. Aortic endothelial function was assessed using organ chamber techniques. Aortic endothelial cells (ECs) were isolated, characterized and their function studied. Results: Compared to controls, ARPKD animals had a decrease in the vasorelaxation to endothelium-dependent vasodilators, even prior to changes in mean arterial pressure or renal function. The abnormal vasoreactivity was corrected with L-arginine (a precursor of nitric oxide, NO), while the expression of endothelial NO synthase (eNOS) was unchanged. Furthermore, isolated ECs from 6-week-old ARPKD animals showed increased oxidative stress, with preserved eNOS expression and abnormal patterns of migration and angiogenic capacity (measured by the scratch and tube formation assays, respectively). Conclusion: ARPKD leads to impairments in aortic vascular function and ECs at an early stage, which can have significant functional consequences, potentially representing a novel therapeutic target in this disease.

Original languageEnglish
Pages (from-to)233-240
Number of pages8
JournalAmerican Journal of Nephrology
Volume38
Issue number3
DOIs
Publication statusPublished - 1 Sep 2013

Keywords

  • Acetylcholine
  • Autosomal inheritance
  • Cardiovascular disease
  • Endothelial dysfunction
  • Polycystic kidney disease

ASJC Scopus subject areas

  • Nephrology

Cite this

Peterson, K. M., Franchi, F., Loeffler, D. L., Psaltis, P. J., Harris, P. C., Lerman, L. O., ... Rodriguez-Porcel, M. (2013). Endothelial dysfunction occurs prior to clinical evidence of polycystic kidney disease. American Journal of Nephrology, 38(3), 233-240. https://doi.org/10.1159/000354236