Evidence suggests that the arachidonic acid metabolite of 12-lipoxygenase, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), not only mediates the effects of angiotensin II (AngII) but also has direct effects on hypertrophy and matrix protein production in vascular smooth muscle cells (VSMC). The current study is aimed at identifying the signaling pathways involved in these events. Treatment of porcine VSMC with 12(S)-HETE led to the activation of Ras and p38 mitogen activated protein kinase (p38MAPK). It also stimulated phosphorylation, DNA binding activity and transactivation of the transcription factor cyclic AMP response element binding protein (CREB). Further 12(S)-HETE induced transcription from a fibronectin promoter containing multiple CRE elements. AngII also induced transactivation of CREB and transcription from the fibronectin promoter. A specific p38MAPK inhibitor (SB202190) as well as a dominant negative Ras mutant (N-17) blocked both 12(S)-HETE and AngII effects. In addition, inhibitors of lipoxygenase also blocked AngII effects. Both 12(S)-HETE and AngII increased cellular hypertrophy with similar potency and this was significantly blocked by SB202190. Stable over expression of murine leukocyte-type 12/15-lipoxygenase in VSMC increased the levels of cell associated 12(S)-HETE as well as basal activity of both ERK and p38MAPKs. Furthermore, these 12-lipoxygenase overexpressing cells displayed significantly greater cellular hypertrophy relative to mock-transfected cells. These results show for the first time that oxidized lipids, such as 12(S)-HETE, can induce VSMC growth and matrix gene expression and mediate growth factor effects via activation of the Ras-MAPK pathway and key target transcription factors.


Gonda Diabetes Center, Beckman Research Institute of the City of Hope, Duarte, CA 91010

Hmmm. Wonder if Molecular's use patent covers metabolites?

"use" patent? I didn't realize you could in any way patent naturally occurring substances. Just designer.

Molecular Nutrition has obtained a patent on the use of arachidonic acid for building muscle. I think they have a case pending against Syntrax but I don't think the patent has ever truly been tested in a court of law.

Despite this, it has been effective at preventing most anyone else from selling arachidonic acid as a sports supplement because Bill has publicly promised to instantly sue anyone who does and the potential costs of litigation are high enough to be a deterrent even if one thinks his patent is bunk.

I don't see how the patent could cover metabolites. Arguably the metabolite could be metabolized from other forms of omega 6 fatty acids.

meh. looks like about 3 jumbo eggs worth per serving. a carton of eggs a day ought to do it. but i guess you're paying him to remove most of the calories and nutrients.

word