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Sphingosine-1-phosphate receptor agonist, FTY720, restores coronary flow reserve in diabetic rats

Hongzeng Xu1, Yuanzhe Jin, Haifeng Ni

  • 1Department of Cardiology, The fourth Affiliated Hospital, China Medical University.

Circulation Journal : Official Journal of the Japanese Circulation Society
|October 17, 2014
PubMed
Abstract

Insights

FTY720 treatment improved coronary microvascular function in diabetic rats. This Sphingosine-1-phosphate receptor agonist therapy attenuated heart changes and enhanced coronary flow reserve in early diabetic models.

Area of Science:

  • Cardiovascular Research
  • Diabetology
  • Pharmacology

Background:

  • Coronary flow reserve (CFR) is impaired in diabetic patients with microvascular complications.
  • Few studies have investigated CFR in well-controlled diabetic models.
  • Early diabetic microvascular dysfunction is a significant concern.

Purpose of the Study:

  • To evaluate the effect of FTY720, a Sphingosine-1-phosphate (S1P) receptor agonist, on coronary microvascular function in early diabetic rats.
  • To assess if FTY720 can improve coronary flow reserve (CFR) in a preclinical model of diabetes.
  • To investigate the impact of S1P receptor agonism on diabetic cardiomyopathy.

Main Methods:

  • Male Sprague-Dawley rats were divided into control, diabetic (streptozotocin-induced), and diabetic treated with FTY720 groups.
  • FTY720 (1.25 mg/kg/day) was administered orally for 9 weeks.
  • Coronary flow reserve (CFR) was assessed using (13)NH3-positron emission tomography.

Main Results:

  • Diabetic rats exhibited significantly impaired CFR compared to control rats (1.39 vs. 1.94, P<0.05).
  • FTY720 treatment attenuated cardiac histological alterations in diabetic rats.
  • FTY720 significantly improved CFR in diabetic rats by 32% (1.84 vs. 1.39, P<0.05).

Conclusions:

  • Long-term therapy with FTY720, an S1P receptor agonist, improved coronary microvascular function in diabetic rats.
  • FTY720 attenuated heart histological changes, suggesting a protective effect on diabetic cardiomyopathy.
  • FTY720 shows potential as a therapeutic agent for improving coronary microvascular function in diabetes.

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