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Central Role For The Cardiotonic Steroid Marinobufagenin In The Pathogenesis Of Experimental Uremic Cardiomyopathy, David Kennedy, Sandeep Vetteth, Sankaridrug Periyasamy, Mohamed Kanj, Larisa Fedorova, Samer Khouri, M. Kahaleh, Zijian Xie, Deepak Malhotra, Nikolai Kolodkin, Edward Lakatta, Olga Fedorova, Alexei Bagrov, Joseph Shapiro
Central Role For The Cardiotonic Steroid Marinobufagenin In The Pathogenesis Of Experimental Uremic Cardiomyopathy, David Kennedy, Sandeep Vetteth, Sankaridrug Periyasamy, Mohamed Kanj, Larisa Fedorova, Samer Khouri, M. Kahaleh, Zijian Xie, Deepak Malhotra, Nikolai Kolodkin, Edward Lakatta, Olga Fedorova, Alexei Bagrov, Joseph Shapiro
Zijian Xie
Patients with chronic renal failure develop a “uremic” cardiomyopathy characterized by diastolic dysfunction, cardiac hypertrophy, and systemic oxidant stress. Patients with chronic renal failure are also known to have increases in the circulating concentrations of the cardiotonic steroid marinobufagenin (MBG). On this background, we hypothesized that elevations in circulating MBG may be involved in the cardiomyopathy. First, we observed that administration of MBG (10 g/kg per day) for 4 weeks caused comparable increases in plasma MBG as partial nephrectomy at 4 weeks. MBG infusion caused increases in conscious blood pressure, cardiac weight, and the time constant for left ventricular relaxation …
Spironolactone Attenuates Experimental Uremic Cardiomyopathy By Antagonizing Marinobufagenin, Jiang Tian, Amjad Shidyak, Sankaridrug Periyasamy, Steven Haller, Mohamed Taleb, Nasser El-Okdi, Jihad Elkareh, Shalini Gupta, Sabry Gohara, Olga Fedorova, Christopher Cooper, Zijian Xie, Deepak Malhorta, Alexei Bagrov, Joseph Shapiro
Spironolactone Attenuates Experimental Uremic Cardiomyopathy By Antagonizing Marinobufagenin, Jiang Tian, Amjad Shidyak, Sankaridrug Periyasamy, Steven Haller, Mohamed Taleb, Nasser El-Okdi, Jihad Elkareh, Shalini Gupta, Sabry Gohara, Olga Fedorova, Christopher Cooper, Zijian Xie, Deepak Malhorta, Alexei Bagrov, Joseph Shapiro
Zijian Xie
Spironolactone has been noted to attenuate cardiac fibrosis. We have observed that the cardiotonic steroid marinobufagenin plays an important role in the diastolic dysfunction and cardiac fibrosis seen with experimental renal failure. We performed the following studies to determine whether and how spironolactone might ameliorate these changes. First, we studied rats subjected to partial nephrectomy or administration of exogenous marinobufagenin. We found that spironolactone (20 mg/kg per day) attenuated the diastolic dysfunction as assessed by ventricular pressure-volume loops and essentially eliminated cardiac fibrosis as assessed by trichrome staining and Western blot. Next, we examined the effects of spironolactone and its …
Marinobufagenin Induces Increases In Procollagen Expression In A Process Involving Protein Kinase C And Fli-1: Implications For Uremic Cardiomyopathy, Jihad Elkareh, Sankaridrug Periyasamy, Amjad Shidyak, Sandeep Vetteth, Jeremy Schroeder, Vanamala Raju, Imad Hariri, Nasser El-Okdi, Shalini Gupta, Larisa Fedorova, Jiang Liu, Olga Fedorova, M. Kahaleh, Zijian Xie, Deepak Malhotra, Dennis Watson, Alexei Bagrov, Joseph Shapiro
Marinobufagenin Induces Increases In Procollagen Expression In A Process Involving Protein Kinase C And Fli-1: Implications For Uremic Cardiomyopathy, Jihad Elkareh, Sankaridrug Periyasamy, Amjad Shidyak, Sandeep Vetteth, Jeremy Schroeder, Vanamala Raju, Imad Hariri, Nasser El-Okdi, Shalini Gupta, Larisa Fedorova, Jiang Liu, Olga Fedorova, M. Kahaleh, Zijian Xie, Deepak Malhotra, Dennis Watson, Alexei Bagrov, Joseph Shapiro
Zijian Xie
The cardiotonic steroid marinobufagenin (MBG) has been implicated in the pathogenesis of experimental uremic cardiomyopathy, which is characterized by progressive cardiac fibrosis. We examined whether the transcription factor Friend leukemia integration-1 (Fli-1) might be involved in this process. Fli-1-knockdown mice demonstrated greater cardiac collagen-1 expression and fibrosis compared with wild-type mice; both developed increased cardiac collagen expression and fibrosis after 5/6 nephrectomy. There was a strong inverse relationship between the expressions of Fli-1 and procollagen in primary culture of rat cardiac and human dermal fibroblasts as well as a cell line derived from renal fibroblasts and MBG-induced decreases in nuclear …