Quantitative Proteomics Reveals Novel Therapeutic and Diagnostic Markers in Hypertension

Overview

Journal BBA Clin

Publisher Elsevier

Specialty Biochemistry

Date 2015 Dec 18

PMID 26672470

Citations 18

Authors

Vittoria Matafora

Laura Zagato

Mara Ferrandi

Isabella Molinari

Gianpaolo Zerbini

Nunzia Casamassima

Chiara Lanzani

Simona Delli Carpini

Francesco Trepiccione

Paolo Manunta

Angela Bachi

Giovambattista Capasso

Affiliations

Soon will be listed here.

Abstract

Hypertension is a prevalent disorder in the world representing one of the major risk factors for heart attack and stroke. These risks are increased in salt sensitive individuals. Hypertension and salt sensitivity are complex phenotypes whose pathophysiology remains poorly understood and, remarkably, salt sensitivity is still laborious to diagnose. Here we present a urinary proteomic study specifically designed to identify urinary proteins relevant for the pathogenesis of hypertension and salt sensitivity. Despite previous studies that underlined the association of UMOD gene variants with hypertension, this work provides novel evidence showing different uromodulin protein level in the urine of hypertensive patients compared to healthy individuals. Notably, we also show that patients with higher level of uromodulin are homozygous for UMOD risk variant and display a decreased level of salt excretion, highlighting the essential role of UMOD in the regulation of salt reabsorption in hypertension. Additionally, we found that urinary nephrin 1, a marker of glomerular slit diaphragm, may predict a salt sensitive phenotype and positively correlate with increased albuminuria associated with this type of hypertension.

Citing Articles

Pathway level metabolomics analysis identifies carbon metabolism as a key factor of incident hypertension in the Estonian Biobank.

Hiie L, Kolde A, Pervjakova N, Reigo A, Abner E, Vosa U Sci Rep. 2025; 15(1):8470.

PMID: 40069276 PMC: 11897224. DOI: 10.1038/s41598-025-92840-w.

Proteomic Analysis of Prehypertensive and Hypertensive Patients: Exploring the Role of the Actin Cytoskeleton.

Al Ashmar S, Anlar G, Krzyslak H, Djouhri L, Kamareddine L, Pedersen S Int J Mol Sci. 2024; 25(9).

PMID: 38732116 PMC: 11084483. DOI: 10.3390/ijms25094896.

Associations of Proteomics With Hypertension and Systolic Blood Pressure: KORA S4/F4/FF4 and KORA Age1/Age2 Cohort Studies.

Lin J, Petrera A, Hauck S, Muller C, Peters A, Thorand B Hypertension. 2024; 81(5):1156-1166.

PMID: 38445514 PMC: 11025610. DOI: 10.1161/HYPERTENSIONAHA.123.22614.

Recent progress in mass spectrometry-based urinary proteomics.

Joshi N, Garapati K, Ghose V, Kandasamy R, Pandey A Clin Proteomics. 2024; 21(1):14.

PMID: 38389064 PMC: 10885485. DOI: 10.1186/s12014-024-09462-z.

Uromodulin biology.

Karagiannidis A, Theodorakopoulou M, Pella E, Sarafidis P, Ortiz A Nephrol Dial Transplant. 2024; 39(7):1073-1087.

PMID: 38211973 PMC: 11210992. DOI: 10.1093/ndt/gfae008.

References

Zimmerli L, Schiffer E, Zurbig P, Good D, Kellmann M, Mouls L . Urinary proteomic biomarkers in coronary artery disease. Mol Cell Proteomics. 2007; 7(2):290-8. DOI: 10.1074/mcp.M700394-MCP200. View

Cubeddu L, Hoffmann I, Aponte L, Nunez-Bogesits R, Medina-Suniaga H, Roa M . Role of salt sensitivity, blood pressure, and hyperinsulinemia in determining high upper normal levels of urinary albumin excretion in a healthy adult population. Am J Hypertens. 2003; 16(5 Pt 1):343-9. DOI: 10.1016/s0895-7061(03)00057-8. View

Snell-Bergeon J, Maahs D, Ogden L, Kinney G, Hokanson J, Schiffer E . Evaluation of urinary biomarkers for coronary artery disease, diabetes, and diabetic kidney disease. Diabetes Technol Ther. 2009; 11(1):1-9. PMC: 2939844. DOI: 10.1089/dia.2008.0040. View

Ogawa K, Wada H, Okada N, Harada I, Nakajima T, Pasquale E . EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture of medullary tubule cells through Rho family GTPases. J Cell Sci. 2006; 119(Pt 3):559-70. DOI: 10.1242/jcs.02777. View

Varghese S, Powell T, Budisavljevic M, Oates J, Raymond J, Almeida J . Urine biomarkers predict the cause of glomerular disease. J Am Soc Nephrol. 2007; 18(3):913-22. PMC: 2733832. DOI: 10.1681/ASN.2006070767. View

Cuccurullo M, Beneduci A, Anand S, Mignani R, Cianciaruso B, Bachi A . Fabry disease: perspectives of urinary proteomics. J Nephrol. 2010; 23 Suppl 16:S199-212. View

Matafora V, DAmato A, Mori S, Blasi F, Bachi A . Proteomics analysis of nucleolar SUMO-1 target proteins upon proteasome inhibition. Mol Cell Proteomics. 2009; 8(10):2243-55. PMC: 2758753. DOI: 10.1074/mcp.M900079-MCP200. View

Hall J, Brands M, Shek E . Central role of the kidney and abnormal fluid volume control in hypertension. J Hum Hypertens. 1996; 10(10):633-9. View

Citterio L, Simonini M, Zagato L, Salvi E, Delli Carpini S, Lanzani C . Genes involved in vasoconstriction and vasodilation system affect salt-sensitive hypertension. PLoS One. 2011; 6(5):e19620. PMC: 3090407. DOI: 10.1371/journal.pone.0019620. View

10.

Cowley Jr A . The genetic dissection of essential hypertension. Nat Rev Genet. 2006; 7(11):829-40. DOI: 10.1038/nrg1967. View

11.

Nakamura T, Kataoka K, Tokutomi Y, Nako H, Toyama K, Dong Y . Novel mechanism of salt-induced glomerular injury: critical role of eNOS and angiotensin II. J Hypertens. 2011; 29(8):1528-35. DOI: 10.1097/HJH.0b013e328348ca95. View

12.

Nagaraj N, Mann M . Quantitative analysis of the intra- and inter-individual variability of the normal urinary proteome. J Proteome Res. 2010; 10(2):637-45. DOI: 10.1021/pr100835s. View

13.

Rossing K, Mischak H, Dakna M, Zurbig P, Novak J, Julian B . Urinary proteomics in diabetes and CKD. J Am Soc Nephrol. 2008; 19(7):1283-90. PMC: 2440301. DOI: 10.1681/ASN.2007091025. View

14.

Ocaranza M, Jalil J . Mitogen-activated protein kinases as biomarkers of hypertension or cardiac pressure overload. Hypertension. 2009; 55(1):23-5. DOI: 10.1161/HYPERTENSIONAHA.109.141960. View

15.

Trudu M, Janas S, Lanzani C, Debaix H, Schaeffer C, Ikehata M . Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression. Nat Med. 2013; 19(12):1655-60. PMC: 3856354. DOI: 10.1038/nm.3384. View

16.

Weinberger M, Fineberg N, FINEBERG S, Weinberger M . Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension. 2001; 37(2 Pt 2):429-32. DOI: 10.1161/01.hyp.37.2.429. View

17.

Shao C, Li M, Li X, Wei L, Zhu L, Yang F . A tool for biomarker discovery in the urinary proteome: a manually curated human and animal urine protein biomarker database. Mol Cell Proteomics. 2011; 10(11):M111.010975. PMC: 3226410. DOI: 10.1074/mcp.M111.010975. View

18.

Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T, Fujita T . Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker. Hypertension. 2006; 47(6):1084-93. DOI: 10.1161/01.HYP.0000222003.28517.99. View

19.

Trepiccione F, Zacchia M, Capasso G . The role of the kidney in salt-sensitive hypertension. Clin Exp Nephrol. 2011; 16(1):68-72. DOI: 10.1007/s10157-011-0489-y. View

20.

Manunta P, Cusi D, Barlassina C, Righetti M, Lanzani C, DAmico M . Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients. Kidney Int. 1998; 53(6):1471-8. DOI: 10.1046/j.1523-1755.1998.00931.x. View