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Abstract: SA-PO1001

Therapeutic Potential of Adipocyte Implantation in Experimental Uremic Cardiomyopathy by Antagonism of Na,K-ATPase Signaling

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Pillai, Sneha S., Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
  • Pereira, Duane Gischewski, Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
  • Chaudhry, Muhammad A., Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
  • Shapiro, Joseph I., Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
  • Sodhi, Komal, Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
Background

The putative method of implantation of adipocytes has been shown to improve systemic inflammatory milieu and metabolic homeostasis in different disease models. We have recently demonstrated that administration of NaKtide, antagonist of Na/K-ATPase signaling, coupled to adipocyte-specific promoter can improve adipocyte phenotype and further attenuated experimental uremic cardiomyopathy. In the present study, we investigated the pathophysiological changes in recipient mice that underwent partial nephrectomy (PNx) surgery and implanted with NaKtide transfected human mesenchymal stem cell (MSC) derived adipocytes.

Methods

Human adipose-derived MSC were transfected with or without lentivirus with adipocyte-specific NaKtide/ scrambled NaKtide and cells were cultured for 15 days with adipocyte differentiation medium. For in vivo adipocyte implantation, Male Fox Chase severe combined immunodeficiency (SCID) (10-12 weeks old) mice were injected with 2×106 adipocytes/ml in the dorsal subcutaneous region of randomly divided groups of mice followed by PNx surgery on the same day. The tissues were harvested for morphological and molecular analyses after 4 weeks of transplantation. Statistical analysis was performed by one-way analysis of variance.

Results

The implantation of NaKtide transfected adipocytes improved adipocyte phenotype, systemic inflammation, and improved cardiac morphological and biochemical function in recipient PNx mice. The changes in plasma microRNA secretion, that act in a paracrine fashion to actively regulate cardiac inflammatory processes, were also ameliorated by NaKtide, implicating a possible mechanism of intra organ crosstalk. The results were compared with the implantation of control and Scrambled NaKtide transfected adipocytes. The study demonstrates that adipocyte-specific NaKtide reprograms the adipocyte phenotype and transplantation of these metabolically healthy adipocytes in PNx exhibits improved systemic and cardiovascular function, through intra-organ crosstalk between adipose and cardiac tissue.

Conclusion

The study establishes the clinical utility of targeting adipocyte Na/K-ATPase signaling as well as explores the therapeutic potential of transplanting healthy adipocytes in attenuating uremic cardiomyopathy.

Funding

  • Other NIH Support