The Adipomyokine Follistatin-like-1 Restores Cardiovascular Function in a Swine Model of Diabetic Myocardial Infarction

  1. Pilar Ruiz-Lozano
  2. Shannon C. Kelly
  3. Kleiton A. S. Silva
  4. Taylor J. Kelty
  5. Amira Amin
  6. Pamela K. Thorne
  7. Christina M. Mueller
  8. Junqing Justin Zhang
  9. Jan R. Ivey
  10. Brittany M. Mezzencella
  11. Ashley N. Clark
  12. Boxiong Deng
  13. Sui Wang
  14. R. Scott Rector
  15. Craig. A. Emter
  16. Mark Mercola
  17. Darla L. Tharp
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Abstract

Obesity, diabetes, and metabolic syndrome increase the incidence and complicate the management of myocardial infarction (MI). Current treatments do not adequately blunt the progression to chronic ischemic heart disease and heart failure, making these diseases the largest cause of mortality worldwide. Insulin resistance and metabolic syndrome were induced in obese Ossabaw swine prior to ischemia/reperfusion injury-induced MI. Subcutaneous administration of the adipomyokine Follistatin-like-1 (recombinant non-glycosylated human FSTL1, ngFSTL1) for two weeks, beginning one month following myocardial infarction, decreased infarct necrosis, increased blood flow, and increased cardiomyocyte proliferation within the infarct region, leading to improved systolic and diastolic function. ngFSTL-1 also enhanced coronary and peripheral vascular function by increasing BK Ca channel-dependent vasodilatory capacity. We conclude that subcutaneous ngFSTL1 ameliorated clinically relevant parameters of cardiac and vascular dysfunction in a preclinical swine model of diabetic MI, and suggest FSTL1 treatment may be broadly efficacious in humans.

ARTICLE HIGHLIGHTS

  • Subcutaneous administration of recombinant human non-glycosylated FSTL1 (ngFSTL1) for 2 weeks, 1 month after infarction/reperfusion injury, improved cardiac function in a preclinical obese swine model of diabetic MI.

  • ngFSTL1 treatment induced cardiomyocyte proliferation and improved coronary perfusion, resulting in reduced necrosis of the infarct region.

  • ngFSTL1 treatment increased blood flow through peripheral arterioles, including cerebral and skeletal muscle, in addition to cardiac arterioles.

  • Systemic delivery of the non-glycosylated form of the adipomyokine FSTL1 might be an effective treatment for diabetic MI.

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  1. Version published to 10.1101/2025.10.15.679868 on bioRxiv