title: Sphingosine-1-phosphate receptor agonist, FTY720, restores coronary flow reserve in diabetic rats.
abstract: BACKGROUND
  Impairment of coronary flow reserve (CFR) has been generally demonstrated in diabetic patients and animals with microvascular complications but without obvious obstructive coronary atherosclerosis. There have been few studies investigating CFR in cases of relatively well-controlled therapy. The purpose of this study is to evaluate the effect of treatment with a Sphingosine-1-phosphate (S1P) receptor potent agonist, FTY720, on early diabetic rats in terms of CFR. METHODS AND RESULTS: Male Sprague-Dawley (SD) rats were divided into 3 groups: (1) streptozotocin-uninjected rats (control rats); (2) streptozotocin-injected hyperglycemic rats (diabetic group); and (3) FTY720-fed and streptozotocin-injected hyperglycemic rats. FTY720 (1.25 mg/kg per day orally) was administrated for 9 weeks in SD rats (from 6 weeks old to 15 weeks old). CFR was evaluated by (13)NH3-positron emission tomography. No obvious pathological changes of macrovascular atherosclerosis were observed in each group. Diabetic rats had impaired CFR compared with the control group (1.39±0.26 vs. 1.94±0.24, P<0.05). Treatment with FTY720 for 9 weeks attenuated the heart histological changes and improved CFR in 32% of diabetic rats (1.84±0.36 vs. 1.39±0.26, P<0.05).
  
  
  CONCLUSIONS
  In summary, long-term therapy with the Sphingosine-1-phosphate receptor agonist, FTY720, improved CFR by attenuating the heart histological changes, and it might have a beneficial effect on coronary microvascular function in diabetic rats.
authors.affiliation: Department of Cardiology, The fourth Affiliated Hospital, China Medical University.
authors.forename: Hongzeng
authors.initials: H
authors.lastname: Xu
authors.forename: Yuanzhe
authors.initials: Y
authors.lastname: Jin
authors.forename: Haifeng
authors.initials: H
authors.lastname: Ni
authors.forename: Shengda
authors.initials: S
authors.lastname: Hu
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000641:Ammonia; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002196:Capillaries / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D000068876:Fingolimod Hydrochloride; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008246:Lysophospholipids; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009590:Nitrogen Radioisotopes; D049268:Positron-Emission Tomography / Q000379:methods; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D008246:Lysophospholipids; D009590:Nitrogen Radioisotopes; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D016212:Transforming Growth Factor beta; C060506:sphingosine 1-phosphate; D000641:Ammonia; D003094:Collagen; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine