Biotech Values

[iwfal]

In mouse models of the genetic disease (Chuvash polycythemia) where HIF is constitutively activated,

Thanks. Hadn't seen that disease before. And your cite had an interesting summary of different known/hypothesized effects - and the most interesting that I hadn't seen before (but have no found multiple other places) is that HIF expression affects cardiomyocyte electrical behavior (a large fraction of the "MI" deaths in renal failure are probably really electrical in nature)

it looks like it might be HIF-2alpha that is the culprit for late onset fibrosis and pulmonary hypertension, with HIF-1alpha being protective.

FWIW I am generally not trying to pin down the exact pathways of importance for each potential AE because, I would argue, it is essentially impossible. Too complex, too interconnected, and we know very little. HIF is clearly a master regulator, and with too many overlaps etc.. E.g. Even the different HIF-PHs overlap significantly wrt which HIF they regulate.

See here for a reasonable summary of the complexity. And almost certainly the complexity has become even worse as we've learned more (this being an old article).

What I am looking for, and comment on, is the list of things to watch for. Previously one of the first 3 on that list was hyperkalemia (hence the post at the start of this thread), but now I need to add another (electrical heart issues).

BTW - just as a closing note: see this article on the role of HIF-1a in fibrosis.