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Abstract: TH-PO624

Eliminating SIRPα Prevents Elevations in Blood Pressure, Suppresses Aldosterone and Cardiac Fibrosis in CKD

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1301 Health Maintenance, Nutrition, and Metabolism: Basic


  • Wu, Jiao, Baylor College of Medicine, Houston, Texas, United States
  • Hu, Zhaoyong, 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

A major consequence of chronic kidney disease (CKD) is uremic cardiomyopathy characterized by cardiac dysfunction and fibrosis. Potential mechanism for the development of CKD-induced cardiomyopathy is increased aldosterone and impairment of intracellular insulin signaling (i.e., dephosphorylation of IRS1 and the insulin receptor) mediated by SIRPα. We reported that SIRPα is activated by inflammation and found that SIRPα is increased in cardiac muscles of mice with CKD. Here we examine the influences of SIRPα on systolic blood pressure (BP), aldosterone and cardiac fibrosis.


We used a global KO of SIRPα (SIRPα Mt) mice and compared them with wild type (WT) mice ± CKD (subtotal nephrectomy). At 8 weeks following CKD, we examined mice for cardiac fibrosis by picrosirius red staining plus systolic BP. To determine if over-expression of SIRPα, affects fibrosis directly we transfected myotubes with a plasmid expressing SIRPα vs. GFP. Finally, we immunoblotted myotubes to evaluate levels of SIRPα, αSMA, pSMAD3, and GAPDH.


Systolic BP levels in WT mice with CKD was higher compared to values in WT control mice. These results mirror increases in aldosterone (2.3-fold higher) vs. WT control mice. Interestingly, SIRPα Mt control mice had lower systolic blood pressures; aldosterone levels were also significantly lower vs. WT control. Additionally, WT mice with CKD displayed 5.2-fold higher levels of aldosterone vs. SIRPα Mt with CKD. Next, we stained for fibrosis markers in WT CKD and SIRPα Mt mice with CKD. Picrosirius red staining revealed a significant reduction in cardiac fibrosis found in SIRPα Mt with CKD compared to values in WT mice with CKD. Myoblasts that had been transfected to overexpress SIRPα vs. GFP plasmids. We determined that fibrosis markers (i.e. αSMA) were significantly increased in myotubes overexpressing SIRPα. Finally, intracellular signaling of TGFß, pSmad3 was significantly stimulated.


Since cardiac fibroblasts express high affinity corticoid receptors for aldosterone, our results suggest that SIRPα contributes to the accumulation of collagen within the myocardial interstitium, leading to cardiac fibrosis and failure in CKD. Thus, suppression of SIRPα undoubtedly plays a critical role in blocking aldosterone secretion and elevations in systolic blood pressure to prevent cardiac fibrosis in CKD.


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