Increased Plasma Chymase Concentration and Mast Cell Chymase Expression in Venous Neointimal Lesions of Patients with CKD and ESRD

Overview

Journal Semin Dial

Specialty Nephrology

Date 2011 Jul 26

PMID 21781173

Citations 14

Authors

Haimanot Wasse

Angel A Rivera

Rong Huang

Deborah E Martinson

Qi Long

William McKinnon

Nawazish Naqvi

Ahsan Husain

Affiliations

Soon will be listed here.

Abstract

The underlying inflammatory component of chronic kidney disease may predispose blood vessels to intimal hyperplasia (IH), which is the primary cause of dialysis access failure. We hypothesize that vascular pathology and markers of IH formation are antecedent to arteriovenous (AV) fistula creation. Blood, cephalic, and basilic vein segments were collected from predialysis chronic kidney disease (CKD) patients with no previous AV access and patients with end-stage renal disease (ESRD). Immunohistochemistry was performed with antibodies against mast cell chymase, transforming growth factor-beta (TGF-β) and interleukin-6 (IL-6), which cause IH. Plasma chymase was measured by ELISA. IH was present in 91% of CKD and 75% of ESRD vein segments. Chymase was abundant in vessels with IH, with the greatest expression in intima and medial layers, and virtually absent in the controls. Chymase colocalized with TGF-β1 and IL-6. Plasma chymase concentration was elevated up to 33-fold in patients with CKD versus controls and was associated with increased chymase in vessels with IH. We show that chymase expression in vessels with IH corresponds with plasma chymase concentrations. As chymase inhibition attenuates IH in animal models, and we find chymase is highly expressed in IH lesions of patients with CKD and ESRD, we speculate that chymase inhibition could have therapeutic value in humans.

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References

Schwab S, Harrington J, Singh A, Roher R, Shohaib S, Perrone R . Vascular access for hemodialysis. Kidney Int. 1999; 55(5):2078-90. DOI: 10.1046/j.1523-1755.1999.00409.x. View

GRIFFIN S, Brown W, MacPherson F, McGrath J, Wilson V, Korsgaard N . Angiotensin II causes vascular hypertrophy in part by a non-pressor mechanism. Hypertension. 1991; 17(5):626-35. DOI: 10.1161/01.hyp.17.5.626. View

Su E, Lombardi D, Siegal J, Schwartz S . Angiotensin II induces vascular smooth muscle cell replication independent of blood pressure. Hypertension. 1998; 31(6):1331-7. DOI: 10.1161/01.hyp.31.6.1331. View

Nishimoto M, Takai S, Kim S, Jin D, Yuda A, Sakaguchi M . Significance of chymase-dependent angiotensin II-forming pathway in the development of vascular proliferation. Circulation. 2001; 104(11):1274-9. DOI: 10.1161/hc3601.094304. View

Beaulieu M, Gabana C, Rose C, Macdonald P, Clement J, Kiaii M . Stenosis at the area of transposition - an under-recognized complication of transposed brachiobasilic fistulas. J Vasc Access. 2007; 8(4):268-74. View

Zhao X, Zhao L, Zheng Q, Su J, Guan H, Shang F . Chymase induces profibrotic response via transforming growth factor-beta 1/Smad activation in rat cardiac fibroblasts. Mol Cell Biochem. 2007; 310(1-2):159-66. DOI: 10.1007/s11010-007-9676-2. View

Hugle T, Hogan V, White K, van Laar J . Mast cells are a source of transforming growth factor β in systemic sclerosis. Arthritis Rheum. 2011; 63(3):795-9. DOI: 10.1002/art.30190. View

Peters S, Trummel M, Meyners W, Koehler B, Westermann K . Valsartan versus ACE inhibition after bare metal stent implantation--results of the VALVACE trial. Int J Cardiol. 2005; 98(2):331-5. DOI: 10.1016/j.ijcard.2004.05.062. View

De Marchi S, Falleti E, Giacomello R, Stel G, Cecchin E, Sepiacci G . Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients. J Am Soc Nephrol. 1996; 7(8):1169-77. DOI: 10.1681/ASN.V781169. View

10.

Peters S, Gotting B, Trummel M, Rust H, Brattstrom A . Valsartan for prevention of restenosis after stenting of type B2/C lesions: the VAL-PREST trial. J Invasive Cardiol. 2001; 13(2):93-7. View

11.

Daemen M, Lombardi D, Bosman F, Schwartz S . Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res. 1991; 68(2):450-6. DOI: 10.1161/01.res.68.2.450. View

12.

Tsai S, Hollenbeck S, Ryer E, Edlin R, Yamanouchi D, Kundi R . TGF-beta through Smad3 signaling stimulates vascular smooth muscle cell proliferation and neointimal formation. Am J Physiol Heart Circ Physiol. 2009; 297(2):H540-9. PMC: 2724222. DOI: 10.1152/ajpheart.91478.2007. View

13.

Chung I, Gold H, Schwartz S, Ikari Y, Reidy M, Wight T . Enhanced extracellular matrix accumulation in restenosis of coronary arteries after stent deployment. J Am Coll Cardiol. 2002; 40(12):2072-81. DOI: 10.1016/s0735-1097(02)02598-6. View

14.

Schulick A, Taylor A, Zuo W, Qiu C, Dong G, Woodward R . Overexpression of transforming growth factor beta1 in arterial endothelium causes hyperplasia, apoptosis, and cartilaginous metaplasia. Proc Natl Acad Sci U S A. 1998; 95(12):6983-8. PMC: 22710. DOI: 10.1073/pnas.95.12.6983. View

15.

Jin D, Ueda H, Takai S, Okamoto Y, Muramatsu M, Sakaguchi M . Effect of chymase inhibition on the arteriovenous fistula stenosis in dogs. J Am Soc Nephrol. 2005; 16(4):1024-34. DOI: 10.1681/ASN.2003121009. View

16.

Roy-Chaudhury P, Kelly B, Miller M, Reaves A, Armstrong J, Nanayakkara N . Venous neointimal hyperplasia in polytetrafluoroethylene dialysis grafts. Kidney Int. 2001; 59(6):2325-34. DOI: 10.1046/j.1523-1755.2001.00750.x. View

17.

Quinn S, Schuman E, Hall L, Gross G, Uchida B, Standage B . Venous stenoses in patients who undergo hemodialysis: treatment with self-expandable endovascular stents. Radiology. 1992; 183(2):499-504. DOI: 10.1148/radiology.183.2.1561357. View

18.

Verrecchia F, Mauviel A . Transforming growth factor-beta signaling through the Smad pathway: role in extracellular matrix gene expression and regulation. J Invest Dermatol. 2002; 118(2):211-5. DOI: 10.1046/j.1523-1747.2002.01641.x. View

19.

Wolf Y, Rasmussen L, Ruoslahti E . Antibodies against transforming growth factor-beta 1 suppress intimal hyperplasia in a rat model. J Clin Invest. 1994; 93(3):1172-8. PMC: 294068. DOI: 10.1172/JCI117070. View

20.

Takai S, Sakonjo H, Fukuda K, Jin D, Sakaguchi M, Kamoshita K . A novel chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[,4-dioxo-1-phenyl-7-(2-pyridyloxy)]2-heptyl]acetamide (NK3201), suppressed intimal hyperplasia after balloon injury. J Pharmacol Exp Ther. 2003; 304(2):841-4. DOI: 10.1124/jpet.102.042580. View