Establishing novel prostacyclin-synthesizing cells with therapeutic potential against heart diseases.
Int J Cardiol
; 163(2): 163-9, 2013 Feb 20.
Article
in En
| MEDLINE
| ID: mdl-21722977
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cells, Cultured
/
Epoprostenol
/
Heart Diseases
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Cardiol
Year:
2013
Document type:
Article
Affiliation country:
United States