Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor Blocker
We previously found that short-term treatment (week 8 to 12 after injury) with high-dose angiotensin receptor blocker (ARB) induced the regression of existing glomerulosclerosis in 5/6 nephrectomy rats. We therefore assessed the effects of long-term intervention with ARB vs. nonspecific antihyperten...
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2022-05-01
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| author | Xuejing Zhu Dan Gao Vittorio Albertazzi Jianyong Zhong Li-Jun Ma Liping Du Yu Shyr Valentina Kon Hai-Chun Yang Agnes B. Fogo |
| author_facet | Xuejing Zhu Dan Gao Vittorio Albertazzi Jianyong Zhong Li-Jun Ma Liping Du Yu Shyr Valentina Kon Hai-Chun Yang Agnes B. Fogo |
| author_sort | Xuejing Zhu |
| collection | DOAJ |
| description | We previously found that short-term treatment (week 8 to 12 after injury) with high-dose angiotensin receptor blocker (ARB) induced the regression of existing glomerulosclerosis in 5/6 nephrectomy rats. We therefore assessed the effects of long-term intervention with ARB vs. nonspecific antihypertensives in this study. Adult rats underwent 5/6 nephrectomy and renal biopsy 8 weeks later. The rats were then divided into three groups with equivalent renal function and glomerular sclerosis and treated with high-dose losartan (ARB), nonspecific antihypertensive triple-therapy (TRX), or left untreated (Control) until week 30. We found that blood pressure, serum creatinine levels, and glomerulosclerosis were lower at sacrifice in ARB and TRX vs. Control. Only ARB reduced proteinuria and maintained the density of WT-1-positive podocytes. Glomerular tufts showed more double-positive cells for CD44, a marker of activated parietal epithelial cells, and synaptopodin after ARB vs. TRX or Control. ARB treatment reduced aldosterone levels. ARB-treated rats had significantly improved survival when compared with TRX or Control. We conclude that both long-term ARB and triple-therapy ameliorate progression, but do not sustain the regression of glomerulosclerosis. ARB resulted in the superior preservation of podocyte integrity and decreased proteinuria and aldosterone, linked to increased survival in the uremic environment. |
| first_indexed | 2024-03-10T01:16:24Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:16:24Z |
| publishDate | 2022-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b86e157b6dec4a03828bc08ad8f9fc712023-11-23T14:08:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012311601810.3390/ijms23116018Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor BlockerXuejing Zhu0Dan Gao1Vittorio Albertazzi2Jianyong Zhong3Li-Jun Ma4Liping Du5Yu Shyr6Valentina Kon7Hai-Chun Yang8Agnes B. Fogo9Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha 410011, ChinaDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USACenter for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USACenter for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USADivision of Pediatric Nephrology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USAWe previously found that short-term treatment (week 8 to 12 after injury) with high-dose angiotensin receptor blocker (ARB) induced the regression of existing glomerulosclerosis in 5/6 nephrectomy rats. We therefore assessed the effects of long-term intervention with ARB vs. nonspecific antihypertensives in this study. Adult rats underwent 5/6 nephrectomy and renal biopsy 8 weeks later. The rats were then divided into three groups with equivalent renal function and glomerular sclerosis and treated with high-dose losartan (ARB), nonspecific antihypertensive triple-therapy (TRX), or left untreated (Control) until week 30. We found that blood pressure, serum creatinine levels, and glomerulosclerosis were lower at sacrifice in ARB and TRX vs. Control. Only ARB reduced proteinuria and maintained the density of WT-1-positive podocytes. Glomerular tufts showed more double-positive cells for CD44, a marker of activated parietal epithelial cells, and synaptopodin after ARB vs. TRX or Control. ARB treatment reduced aldosterone levels. ARB-treated rats had significantly improved survival when compared with TRX or Control. We conclude that both long-term ARB and triple-therapy ameliorate progression, but do not sustain the regression of glomerulosclerosis. ARB resulted in the superior preservation of podocyte integrity and decreased proteinuria and aldosterone, linked to increased survival in the uremic environment.https://www.mdpi.com/1422-0067/23/11/6018ARBglomerulosclerosissurvivalpodocyteproteinuria |
| spellingShingle | Xuejing Zhu Dan Gao Vittorio Albertazzi Jianyong Zhong Li-Jun Ma Liping Du Yu Shyr Valentina Kon Hai-Chun Yang Agnes B. Fogo Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor Blocker International Journal of Molecular Sciences ARB glomerulosclerosis survival podocyte proteinuria |
| title | Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor Blocker |
| title_full | Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor Blocker |
| title_fullStr | Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor Blocker |
| title_full_unstemmed | Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor Blocker |
| title_short | Podocyte-Related Mechanisms Underlying Survival Benefit of Long-Term Angiotensin Receptor Blocker |
| title_sort | podocyte related mechanisms underlying survival benefit of long term angiotensin receptor blocker |
| topic | ARB glomerulosclerosis survival podocyte proteinuria |
| url | https://www.mdpi.com/1422-0067/23/11/6018 |
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