Expression of thromboxane synthase, prostacyclin synthase and thromboxane receptor in atherosclerotic lesions: correlation with plaque composition.
OBJECTIVE
Prostaglandins, such as thromboxane A(2) (TxA(2)) and prostacyclin (PGI(2)), are bioactive lipid mediators that are implicated in the pathogenesis of atherosclerosis. In the current study, we tested the hypothesis that thromboxane synthase (TXAS), prostacyclin synthase (PGIS) and thromboxane receptor (TP) are expressed within the atherosclerotic lesion.


METHODS
Atherosclerotic aorta segments were obtained from low-density lipoprotein receptor deficient (LDL r-KO) mice on a high fat diet. Expression levels of TXAS, PGIS and TP were evaluated by real-time quantitative reverse transcription PCR, and immunohistochemistry; TxA(2) and PGI(2) biosynthesis was also assayed.


RESULTS
After 8 weeks on the fat diet, aortic arches from LDL r-KO mice showed a significant increase in PGIS, TXAS, TP mRNA, TxA(2) and PGI(2) levels, when compared with controls. By contrast, after 16 weeks on the high fat diet PGIS and PGI(2) were significantly reduced, whereas TXAS and TP message and protein and TxA(2) levels were further and significantly increased in the atherosclerotic tissues when compared with the 8-week group. These changes correlated with the cellular composition of the atherosclerotic lesions.


CONCLUSIONS
TXAS, PGIS and TP are all present within the atherosclerotic lesion areas, their levels change during progression of atherogenesis and contribute to TxA(2) and PGI(2) formation.
Cyrus
Tillmann
T
Department of Cardiology, Washington University, St. Louis, MO, United States.
Ding
Tao
T
Praticò
Domenico
D
D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004041:Dietary Fats; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry / Q000379:methods; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis*; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011453:Prostaglandins / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013930:Thromboxane-A Synthase / Q000096:biosynthesis*; D013931:Thromboxanes / Q000378:metabolism
D004041:Dietary Fats; D008055:Lipids; D011453:Prostaglandins; D017482:Receptors, Thromboxane; D013931:Thromboxanes; D003577:Cytochrome P-450 Enzyme System; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase