title: Establishing novel prostacyclin-synthesizing cells with therapeutic potential against heart diseases.
abstract: BACKGROUND
  For decades, there have been many ongoing attempts to use prostaglandin I(2) (PGI(2)) to treat heart diseases, such as pulmonary arterial hypertension. However, the short half life of PGI(2) has limited the therapeutic impact potential.
  
  
  METHODS
  Here, we have engineered a novel adipose tissue-derived cell that constantly produces PGI(2,) through transfecting of an engineered cDNA of a hybrid enzyme (human COX-1-10-aa-PGIS) which has superior triple catalytic functions in directly converting arachidonic acid into PGI(2).
  
  
  RESULTS
  The gene-transfected cells were further converted into a stable cell line, in which cells constantly express the hybrid enzyme and are capable of producing large-amounts of PGI(2). In a comparison between un-transfected- and gene-transfected cells, it was determined that the majority of the endogenous AA metabolism shifted from that of unwanted PGE(2) (in un-transfected cells) to that of the preferred PGI(2) (in gene-transfected cells) with a PGI(2)/PGE(2) ratio change from 0.03 to 25. The PGI(2)-producing cell line not only exhibited an approximate 50-fold increase in PGI(2) biosynthesis, but also demonstrated superior anti-platelet aggregation in vitro, and increased reperfusion in the mouse ischemic hindlimb model in vivo.
  
  
  CONCLUSIONS
  The cells, which have an ability to increase the biosynthesis of the vascular protector, PGI(2), while reducing that of the vascular inflammatory mediator, PGE(2), provide a dual effect on vascular protection, which is not available through any existing drug treatments. Thus, the current finding has potential to be an experimental intervention for PGI(2)-deficient heart diseases, such as pulmonary arterial hypertension.
authors: Center for Experimental Therapeutics and PharmacoInformatics, Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX, USA. khruan@uh.edu
authors: Ke-He
authors: KH
authors: Ruan
authors: Anita
authors: A
authors: Mohite
authors: Shui-Ping
authors: SP
authors: So
authors: Cheng-Huai
authors: CH
authors: Ruan
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis*; D006331:Heart Diseases / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D014162:Transfection
chemical_list: D011464:Epoprostenol; D051545:Cyclooxygenase 1