Intracellular Calcium Increases in Vascular Smooth Muscle Cells with Progression of Chronic Kidney Disease in a Rat Model

Overview

Journal Nephrol Dial Transplant

Publisher Oxford University Press

Specialties General Surgery
Nephrology

Date 2016 Aug 12

PMID 27510531

Citations 14

Authors

Stacey Dineen Rodenbeck

Chad A Zarse

Mikaela L McKenney-Drake

Rebecca S Bruning

Michael Sturek

Neal X Chen

Sharon M Moe

Affiliations

Soon will be listed here.

Abstract

Background: Vascular smooth muscle cells (VSMCs) exhibit phenotypic plasticity, promoting vascular calcification and increasing cardiovascular risk. Changes in VSMC intracellular calcium ([Ca 2+ ] i ) are a major determinant of plasticity, but little is known about changes in [Ca 2+ ] i in chronic kidney disease (CKD). We have previously demonstrated such plasticity in aortas from our rat model of CKD and therefore sought to examine changes in [Ca 2+ ] i during CKD progression.

Materials And Methods: We examined freshly isolated VSMCs from aortas of normal rats, Cy/+ rats (CKD) with early and advanced CKD, and advanced CKD rats treated without and with 3% calcium gluconate (CKD + Ca 2+ ) to lower parathyroid hormone (PTH) levels. [Ca 2+ ] i was measured with fura-2.

Results: Cy/+ rats developed progressive CKD, as assessed by plasma levels of blood urea nitrogen, calcium, phosphorus, parathyroid hormone and fibroblast growth factor 23. VSMCs isolated from rats with CKD demonstrated biphasic alterations in resting [Ca 2+ ] i : VSMCs from rats with early CKD exhibited reduced resting [Ca 2+ ] i , while VSMCs from rats with advanced CKD exhibited elevated resting [Ca 2+ ] i . Caffeine-induced sarcoplasmic reticulum (SR) Ca 2+ store release was modestly increased in early CKD and was more drastically increased in advanced CKD. The advanced CKD elevation in SR Ca 2+ store release was associated with a significant increase in the activity of the sarco-endoplasmic reticulum Ca 2+ ATPase (SERCA); however, SERCA2a protein expression was decreased in advanced CKD. Following SR Ca 2+ store release, recovery of [Ca 2+ ] i in the presence of caffeine and extracellular Ca 2+ was attenuated in VSMCs from rats with advanced CKD. This impairment, together with reductions in expression of the Na + /Ca 2+ exchanger, suggest a reduction in Ca 2+ extrusion capability. Finally, store-operated Ca 2+ entry (SOCE) was assessed following SR Ca 2+ store depletion. Ca 2+ entry during recovery from caffeine-induced SR Ca 2+ store release was elevated in advanced CKD, suggesting a role for exacerbated SOCE with progressing CKD.

Conclusions: With progressive CKD in the Cy/+ rat there is increased resting [Ca 2+ ] i in VSMCs due, in part, to increased SOCE and impaired calcium extrusion from the cell. Such changes may predispose VSMCs to phenotypic changes that are a prerequisite to calcification.

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References

Neven E, DHaese P . Vascular calcification in chronic renal failure: what have we learned from animal studies?. Circ Res. 2011; 108(2):249-64. DOI: 10.1161/CIRCRESAHA.110.225904. View

Moe S, Drueke T, Lameire N, Eknoyan G . Chronic kidney disease-mineral-bone disorder: a new paradigm. Adv Chronic Kidney Dis. 2007; 14(1):3-12. DOI: 10.1053/j.ackd.2006.10.005. View

Gutierrez O, Januzzi J, Isakova T, Laliberte K, Smith K, Collerone G . Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation. 2009; 119(19):2545-52. PMC: 2740903. DOI: 10.1161/CIRCULATIONAHA.108.844506. View

Lajdova I, Spustova V, Oksa A, Kaderjakova Z, Chorvat Jr D, Morvova Jr M . The Impact of Vitamin D3 Supplementation on Mechanisms of Cell Calcium Signaling in Chronic Kidney Disease. Biomed Res Int. 2015; 2015:807673. PMC: 4434177. DOI: 10.1155/2015/807673. View

Berra-Romani R, Mazzocco-Spezzia A, Pulina M, Golovina V . Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture. Am J Physiol Cell Physiol. 2008; 295(3):C779-90. PMC: 2544451. DOI: 10.1152/ajpcell.00173.2008. View

Neudecker S, Walz R, Menon K, Maier E, Bihoreau M, Obermuller N . Transgenic overexpression of Anks6(p.R823W) causes polycystic kidney disease in rats. Am J Pathol. 2010; 177(6):3000-9. PMC: 2993307. DOI: 10.2353/ajpath.2010.100569. View

Hoff S, Halbritter J, Epting D, Frank V, Nguyen T, van Reeuwijk J . ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nat Genet. 2013; 45(8):951-6. PMC: 3786259. DOI: 10.1038/ng.2681. View

Touchberry C, Green T, Tchikrizov V, Mannix J, Mao T, Carney B . FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy. Am J Physiol Endocrinol Metab. 2013; 304(8):E863-73. PMC: 3625783. DOI: 10.1152/ajpendo.00596.2012. View

Fadda G, Hajjar S, Perna A, Zhou X, Lipson L, Massry S . On the mechanism of impaired insulin secretion in chronic renal failure. J Clin Invest. 1991; 87(1):255-61. PMC: 295039. DOI: 10.1172/JCI114979. View

10.

Tada Y, Yano S, Yamaguchi T, Okazaki K, Ogawa N, Morita M . Advanced glycation end products-induced vascular calcification is mediated by oxidative stress: functional roles of NAD(P)H-oxidase. Horm Metab Res. 2012; 45(4):267-72. DOI: 10.1055/s-0032-1329965. View

11.

Lipskaia L, Monte F, Capiod T, Yacoubi S, Hadri L, Hours M . Sarco/endoplasmic reticulum Ca2+-ATPase gene transfer reduces vascular smooth muscle cell proliferation and neointima formation in the rat. Circ Res. 2005; 97(5):488-95. DOI: 10.1161/01.RES.0000180663.42594.aa. View

12.

Shroff R, Long D, Shanahan C . Mechanistic insights into vascular calcification in CKD. J Am Soc Nephrol. 2012; 24(2):179-89. DOI: 10.1681/ASN.2011121191. View

13.

Pai A, Leaf E, El-Abbadi M, Giachelli C . Elastin degradation and vascular smooth muscle cell phenotype change precede cell loss and arterial medial calcification in a uremic mouse model of chronic kidney disease. Am J Pathol. 2011; 178(2):764-73. PMC: 3069837. DOI: 10.1016/j.ajpath.2010.10.006. View

14.

Polak-Jonkisz D, Zwolinska D, Purzyc L, Musial K . Ca2+-Mg2+-dependent ATP-ase activity and calcium homeostasis in children with chronic kidney disease. Pediatr Nephrol. 2006; 22(3):414-9. DOI: 10.1007/s00467-006-0329-6. View

15.

Zimmerman M, Takapoo M, Jagadeesha D, Stanic B, Banfi B, Bhalla R . Activation of NADPH oxidase 1 increases intracellular calcium and migration of smooth muscle cells. Hypertension. 2011; 58(3):446-53. PMC: 3160712. DOI: 10.1161/HYPERTENSIONAHA.111.177006. View

16.

Wamhoff B, Bowles D, McDonald O, Sinha S, Somlyo A, Somlyo A . L-type voltage-gated Ca2+ channels modulate expression of smooth muscle differentiation marker genes via a rho kinase/myocardin/SRF-dependent mechanism. Circ Res. 2004; 95(4):406-14. DOI: 10.1161/01.RES.0000138582.36921.9e. View

17.

Moe S, Radcliffe J, White K, Gattone 2nd V, Seifert M, Chen X . The pathophysiology of early-stage chronic kidney disease-mineral bone disorder (CKD-MBD) and response to phosphate binders in the rat. J Bone Miner Res. 2011; 26(11):2672-81. DOI: 10.1002/jbmr.485. View

18.

Hajjar S, Smogorzewski M, Zayed M, Fadda G, Massry S . Effect of chronic renal failure on Ca2+ ATPase of brain synaptosomes. J Am Soc Nephrol. 1991; 2(6):1115-21. DOI: 10.1681/ASN.V261115. View

19.

Taki K, Takayama F, Tsuruta Y, Niwa T . Oxidative stress, advanced glycation end product, and coronary artery calcification in hemodialysis patients. Kidney Int. 2006; 70(1):218-24. DOI: 10.1038/sj.ki.5000330. View

20.

Shroff R, McNair R, Skepper J, Figg N, Schurgers L, Deanfield J . Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification. J Am Soc Nephrol. 2009; 21(1):103-12. PMC: 2799273. DOI: 10.1681/ASN.2009060640. View