Identification of Cathepsin L as a Potential Sex-Specific Biomarker for Renal Damage
| Autor: | Daniel S. Strasser, Changbin Qiu, Manuel Stritt, Anna K. Stalder, Bérengère Renault, Martine Clozel, Rolf Studer, Daniel Wanner, Katalin Kauser, Walter Fischli, Oliver Nayler, Patrick Hess, Nina Killer, Hervé Farine, Yasmina Bauer, Axel Klenk |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Cathepsin L Urinary system Angiotensinogen Renal function Blood Pressure Enzyme-Linked Immunosorbent Assay Kidney Renal Circulation Rats Sprague-Dawley Renin-Angiotensin System Internal medicine Renin Internal Medicine medicine Animals Humans Oligonucleotide Array Sequence Analysis Analysis of Variance Sex Characteristics Proteinuria biology Reverse Transcriptase Polymerase Chain Reaction medicine.disease Immunohistochemistry Rats Endocrinology Tissue Array Analysis Renal blood flow Albuminuria biology.protein Biomarker (medicine) Female Vascular Resistance Rats Transgenic medicine.symptom Biomarkers Glomerular Filtration Rate Kidney disease |
| Zdroj: | Hypertension. 57:795-801 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.110.157206 |
| Popis: | The renin-angiotensin system is a well-known regulator of blood pressure and plays an important role in the pathogenesis of cardiovascular disease and renal damage. Genetic factors, including single nucleotide polymorphisms and sex, are increasingly recognized as potential risk factors for the development of cardiovascular disease. Double transgenic rats (dTGRs), harboring human renin and angiotensinogen genes, were used in this study to investigate potential sex differences influencing renal function and renal gene expression. dTGR males and females had comparable increases in blood pressure, whereas body weight, albuminuria/proteinuria, and urine flow rate were higher in males. At 8 weeks of age, renal plasma flow and glomerular filtration rate were proportionally lower in males, and renal vascular resistance tended to be higher. Males developed more severe tubulointerstitial and vascular lesions. By the end of week 8, 40%of the males but none of the females had died. Genome expression studies were performed with RNA from kidneys of 7-week–old male and female dTGRs and control rats to further investigate the sex-related differences on a molecular level. Forty-five genes showed sex-dependent expression patterns in dTGRs that were significantly different compared to controls. Cathepsin L, one of the genes differentially expressed between the sexes, was also shown to be strongly associated with the degree of renal injury. In dTGRs, urinary cathepsin L at week 7 was higher in males (nanograms per 24 hours: male, 512±163; female, 132±70). These results reveal a potential new biomarker for the personalized diagnosis and management of chronic kidney disease. |
| Databáze: | OpenAIRE |
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