ORCID Profile
0000-0001-8011-8882
Current Organisation
Mayo Clinic
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Publisher: S. Karger AG
Date: 2013
DOI: 10.1159/000354236
Abstract: b i Objective: /i /b 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. b i Methods: /i /b 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. b i Results: /i /b 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 smlcap L /smlcap -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). b i Conclusion: /i /b 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.
Publisher: Elsevier BV
Date: 07-2013
Publisher: Wiley
Date: 02-2013
DOI: 10.1111/MICC.12022
Publisher: SAGE Publications
Date: 09-2015
Abstract: Polycystic kidney disease (PKD) is a common cause of end-stage renal failure, for which there is no accepted treatment. Progenitor and stem cells have been shown to restore renal function in a model of renovascular disease, a disease that shares many features with PKD. The objective of this study was to examine the potential of adult stem cells to restore renal structure and function in PKD. Bone marrow-derived mesenchymal stromal cells (MSCs, 2.5 × 10 5 ) were intrarenally infused in 6-week-old PCK rats. At 10 weeks of age, PCK rats had an increase in systolic blood pressure (SBP) versus controls (126.22 ± 2.74 vs. 116.45 ± 3.53 mmHg, p 0.05) and decreased creatinine clearance (3.76 ± 0.31 vs. 6.10 ± 0.48 μl/min/g, p 0.01), which were improved in PKD animals that received MSCs (SBP: 114.67 ± 1.34 mmHg, and creatinine clearance: 4.82 ± 0.24 μl/min/g, p = 0.001 and p = 0.003 vs. PKD, respectively). MSCs preserved vascular density and glomeruli diameter, measured using microcomputed tomography. PCK animals had increased urine osmolality (843.9 ± 54.95 vs. 605.6 ± 45.34 mOsm, p 0.01 vs. control), which was improved after MSC infusion and not different from control (723.75 ± 56.6 mOsm, p = 0.13 vs. control). Furthermore, MSCs reduced fibrosis and preserved the expression of proangiogenic molecules, while cyst size and number were unaltered by MSCs. Delivery of exogenous MSCs improved vascular density and renal function in PCK animals, and the benefit was observed up to 4 weeks after a single infusion. Cell-based therapy constitutes a novel approach in PKD.
No related grants have been discovered for Karen Peterson.