Effect of Preeclampsia Serum on Human Uterine Spiral Artery

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Re: Effect of Preeclampsia Serum on Human Uterine Spiral Art

Post by caryn » Wed Jan 25, 2012 01:29 am

Also, this doesn't suggest that it's just a problem with us that causes preeclampsia. It's *hard* to culture trophoblastic cells, and one of the handful of things that makes creating immortal cell lines easier is virulence, so it's possible that the particular trophoblastic cells that are serving as laboratory culture these days are more likely to be invasive PE-causing cells than ones we weren't able to culture. Hardier, more likely to thrive in difficult environments, etc. Who knows?

Re: Effect of Preeclampsia Serum on Human Uterine Spiral Art

Post by caryn » Wed Jan 25, 2012 08:55 am

Kerisue, not exactly - I have relatives and friends with university access, and depending on which library they're tapping, I email people and beg for articles. My husband and cousin and brother-in-law indulge me, and so do my researcher friends. (The library matters because small state schools without med schools subscribe to fewer journals than big Research 1 universities.)

I also live 6 miles from the U of Pittsburgh's library, so take myself over and make copies to read later.

Email is faster. :)

Rosalinda, this is just basic research - nothing on the launch pad yet for treatment. This is more like bits of equipment being piled into the storage bay that could eventually be used by clever people to help assemble a rocket. Here's what I got out of the abstract ('cause I haven't been to the library yet, and this isn't in print yet in any case!):

It's been known for a while that the spiral arteries are bolloxed in preeclampsia. There's been some debate (even some here) about the way this might or might not cause PE, because of the "problem of induction" - is this just correlated, or is it causal, and how would you tell for sure, anyway? Are the arteries constricted because of something that is not working properly in the placenta? Because of something in the maternal response? Because of both? And basic research on this question is ridiculously difficult. Some people have ethical objections to tests on blastocysts, we can't readily establish cell lines of decidua or trophoblast, etc. etc. ad nauseum.

So. There exist a handful of established cytotrophoblastic cell lines - these are the cells that comprise the outer layer of the blastocyst, that are paternal (because the maternal genes have been silenced), that form the leading edge of the placenta. They "induce apoptosis" - ie trigger cell death - in the maternal cells that line the spiral arteries, and replace them with themselves. This lets them ignore maternal instructions to constrict the size of the blood vessel. Instead the cells prop the ends of the arteries open, as flared out as possible, which results (in the words of one of the CME researchers in November at Saving Grace) in "a big ol' honking blood jet" that bathes the placenta in blood, nutrients, and oxygen.

This doesn't work, for us. The arteries don't remodel properly. (Google "spiral artery remodel preeclampsia" for a ton of slides illustrating this.)

So the researchers here took a cultures of cytotrophoblasts and exposed them to either serum from normal pregnancies, or serum from preeclamptics. And the preeclamptic blood did several interesting things: it turned down the production of the proteins that allow the cytrotrophoblasts to work, it enhanced the survival of the maternal cells lining the vessels, and apparently it did this by turning down production of the cellular "locks" on the maternal cells and production of the cellular "keys" on the paternal cells.

Theory says: our bodies don't realize we've invented Caesareans, so they go to a lot of trouble to keep us from hosting placentas they think won't fit out. This is part of how they do that.

Re: Effect of Preeclampsia Serum on Human Uterine Spiral Art

Post by rosalinda » Tue Jan 24, 2012 10:53 am

can you explain it a little more? I don't understand, oh and also ...what does this mean for ME?

Re: Effect of Preeclampsia Serum on Human Uterine Spiral Art

Post by kerisue » Tue Jan 24, 2012 09:58 am

Do you have access to full text articles Caryn?

Effect of Preeclampsia Serum on Human Uterine Spiral Artery

Post by caryn » Tue Jan 24, 2012 03:28 am

In a model of CTBs cocultured with HUSASMCs, preeclamptic serum effectively decreased the invasive ability and FasL mRNA expression of the CTBs. Preeclampsia serum also increased HUSASMC viability, decreased their apoptotic rate, and decreased the expression of Fas mRNA and protein. Conclusion: The abnormal invasive ability of CTBs and decreased expression of the Fas/FasL system may be directly involved in the defective remodeling of the uterine spiral arteries during preeclampsia. Furthermore, the decrease in HUSASMC apoptosis may be related to the abnormal expression of Fas/FasL.

http://www.ncbi.nlm.nih.gov/pubmed/22248491

This is WAY COOL. These researchers figured out that yeah, there's stuff in our blood that is keeping cytotrophoblastic cells (CTBs) from advancing into the spiral arteries and remodeling them. And roughly which ligands it's messing with. I need to pull the full-text to say more.

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