Activation of peroxisome proliferator-activated receptors alpha and gamma1 inhibits human smooth muscle cell proliferation.
Atherosclerotic lesions occur as a result of excess lipid deposition within the vascular tissues. The peroxisome proliferator-activated receptors (PPARs) present in adipose and hepatic tissues have been shown to promote fatty acid oxidation and lipid storage. An immunohistochemical assessment of PPARalpha and PPARgamma revealed both proteins were also present in the medial and intimal layers of human arteries, predominately in regions containing smooth muscle cells. In agreement with this observation, smooth muscle cells isolated from these vessels were found by RT-PCR to express both PPARalpha and PPARgamma1. The functionality of these receptors was tested with selective PPAR agonists. Mitogenic stimulation of smooth muscle cell proliferation was blocked by 15d-PGJ2, a PPARgamma agonist, as well as by WY14643, a PPARalpha agonist. These data indicate PPAR activation by selective agonists could influence lesion progression directly, as well as indirectly through reductions in serum lipoprotein and triglyceride levels.
Zahradka
Peter
P
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB, Canada. peterz@sbrc.ca
Yurkova
Natalia
N
Litchie
Brenda
B
Moon
Michael C
MC
Del Rizzo
Dario F
DF
Taylor
Carla G
CG
D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
C477819:15-deoxyprostaglandin J2; D011743:Pyrimidines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C006253:pirinixic acid; D015230:Prostaglandin D2