Kidney Week

Abstract: SA-PO997

The Role of the Adipocyte Na/K-ATPase Oxidant Amplification Loop in Uremic Cardiomyopathy

Session Information

• Hypertension and CVD: Mechanisms - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1403 Hypertension and CVD: Mechanisms

Authors

• Sodhi, Komal, Marshall University Joan C. Edwards School of Medicine, Huntington, West Virginia, United States

Komal Sodhi,

• Chaudhry, Muhammad A., Marshall University School of Medicine, Huntington, West Virginia, United States

Muhammad A. Chaudhry,

• Klug, Rebecca Lynn, Marshall University, Joan C. Edwards School of Medicine , Huntington, West Virginia, United States

Rebecca Lynn Klug,

• Pratt, Rebecca, Marshall University School of Medicine, Huntington, West Virginia, United States

Rebecca Pratt,

• Brickman, Cameron, Marshall University JCESOM, Huntington, West Virginia, United States

Cameron Brickman,

• Lakhani, Hari Vishal, Marshall University, Huntington, West Virginia, United States

Hari Vishal Lakhani,

• Liu, Jiang, Marshall University JCE School of Medicine, Huntington, West Virginia, United States

Jiang Liu,

• Xie, Zi-jian, Marshall University, Huntington, West Virginia, United States

Zi-jian Xie,

• Shapiro, Joseph I., Marshall University School of Medicine, Huntington, West Virginia, United States

Joseph I. Shapiro,

Background

Chronic kidney disease upregulates oxidative stress, increasing morbidity and mortality of cardiovascular disease. We demonstrated that administration of pNaKtide, a peptide mimicking control of Src activation via plasmalemmal Na/K-ATPase, halts development and reverses experimental uremic cardiomyopathy. Adipocyte contribution to systemic disease is an important topic; we investigated the expression of adipocyte production of NaKtide, a component of pNaKtide lacking the cell-permeant sequence derived from TAT, to observe the affects on the development of uremic cardiomyopathy. We examined high fat diet (HFD) on the development of cardiomyopathy in the model involving partial nephrectomy (PNx).

Methods

C57Bl6 mice, 10 weeks old male, subjected to 2-part sham or PNx surgical procedure and injected with lentivirus+adiponectin+NaKtide. Then randomly divided into 4 groups: (1) Sham, (2) Sham+NaKtide, (3) PNx (4) PNx+NaKtide. Metabolic function was assessed via oxygen consumption cages, blood pressure readings, glucose tolerance tests, and echocardiography. Following four weeks of treatment, the animals were sacrificed, tissues and fluid samples were collected.

Results

Plasma creatinine levels significantly increased with PNx compared to Naktide treatment (p≤0.05). Histological analysis of cardiac tissue shows increased fibrosis with PNx and decreased with NaKtide treatment (p≤0.05). Mice developed cardiomyopathy with diastolic dysfunction and left ventricular hypertrophy 4 weeks after PNx. Concomitant administration of HFD worsened changes and caused decreased ejection fraction and fractional shortening (both p<0.01). Transfection with adiponectin promoting lentivirus for NaKtide expression normalized cardiac abnormalities in PNx and PNx + HFD. Normal hematocrit values, IL6 and TNFa were seen with NaKtide transfection as opposed PNx and PNx + HFD (both p<0.01). Transfection with empty vector or NaKtide with myoD promoter did not affect any measurements.

Conclusion

Our study demonstrates that adipocytes contribute to oxidant stress associated with uremic cardiomyopathy. These data suggest that the adipocyte Na/K-ATPase oxidant amplification loop may be a viable clinical target for the prevention or treatment of uremic cardiomyopathy.

Funding

• Private Foundation Support