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Kidney Week

Abstract: SA-PO964

Circulating SIRPα Stimulates CKD-Induced Cardiomyopathy

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

  • Wu, Jiao, Baylor College of Medicine, Houston, Texas, United States
  • Mitch, William E., Baylor College of Medicine, Houston, Texas, United States
  • Thomas, Sandhya S., Baylor College of Medicine, Houston, Texas, United States
Background

A major etiology of chronic kidney disease (CKD) is insulin resistance in CKD-induced cardiomyopathy. We have discovered a potential driver of insulin resistance, signal regulatory protein alpha (SIRPα) that circulates in response to CKD which adversely influences myocardial muscle.

Methods

Myotubes and cardiomyocytes, but not adipocytes treated with high glucose, or cardiomyocytes treated with uremic toxins stimulated secretion of SIRPα in culture media. Next, to determine myocardial-specific effects of suppressing SIRPα in CKD, csSIRPα-/- mice were created and subjected to subtotal nephrectomy and compared to flox mice with CKD. In vivo M-mode echocardiography imaging was utilized to determine myocardial function. csSIRPα-/-mice with CKD displayed improved ejection fraction %, fractional shortening % , and cardiac output when compared to flox littermate control mice with CKD.

Results

Myotubes and cardiomyocytes, but not adipocytes treated with high glucose, or cardiomyocytes treated with uremic toxins stimulated secretion of SIRPα in culture media. Next, to determine myocardial-specific effects of suppressing SIRPα in CKD, csSIRPα-/- mice were created and subjected to subtotal nephrectomy and compared to flox mice with CKD. In vivo M-mode echocardiography imaging was utilized to determine myocardial function. csSIRPα-/- mice with CKD displayed improved ejection fraction %, fractional shortening % , and cardiac output when compared to flox littermate control mice with CKD

Conclusion

These results suggest that skeletal or cardiac muscle are the origin of circulating SIRPα in response to uremia or hyperglycemia which stimulates its release. Importantly, cardioprotection from CKD was observed with myocardial suppression of SIRPα.

Funding

  • Private Foundation Support