Lipopolysaccharide as a pro-inflammatory stimulus modulates vascular remodeling in early gestation. A possible immunomodulatory role of lysophosphatidic acid.

BELTRAME JS; CAÑUMIL, VA; DE LA CRUZ BORTHIRY, FL; FRANCHI, AM; RIBEIRO, ML

Congreso; 2021 Congreso de la International Federation of Placenta Associations (IFPA); 2021

The origin of implantation failures isunknown in at least 50% of cases. One hypothesis holds that subclinicalinfections cause an imbalance in pro- vs anti-inflammatory responses, withsevere consequences for pregnancy progress. Preeclamptic patients have anincreased proinflammatory profile that correlates with defects in uterineartery remodeling and trophoblast migration. In this context, we postulate thatvascular remodeling could be a target of pro-inflammatory situations since itis highly regulated by the trophoblast and by the decidual immune system. Also,we hypothesize that lysophosphatidic acid (LPA), a phosphorylated lipid withpro-implantation and vascular actions, could modulate the inflammatoryresponse.Wistar female rats on day 5 of gestationreceived an intraperitoneal injection of lipopolysaccharide (LPS, 40 μg/mg) or vehicle. E. Coli LPS was used as a pro-inflammatory stimulus.Animals were euthanized on day 9 of gestation to study the ongoing vascularremodeling. Furthermore, we adopted an  in vitro pharmacological approach to investigatewhether LPA acts as an immunomodulatory lipid that regulates trophoblastfunctions and facilitates spiral artery remodeling. These experiments werecarried out on a first-trimester human trophoblast cell line (HTR-8/SVneo).HTR-8/SVneo were incubated with LPA (10 µM) and LPS 0.1 µg/ml to mimic sterileinflammation, or 10 µg/ml to elicit a pro-inflammatory response. Theendovascular trophoblast response was evaluated by tube formation and migrationassays. Differences between means were significant when p<0.05. Our invivo results indicate that LPS produces an increase in the transversallength of the uterine and arcuate arteries, the main vessels supplying theimplantation sites. Also, LPS implantation sites are larger than the control.Moreover, invitro experiments suggest that LPA regulates the actionof LPS on trophoblast migration and endovascular response.  Overall, our preliminary findings showthat inflammation could affect vascular remodeling in early gestation, and LPAmay exert immunomodulatory actions.@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-520082689 -1073697537 9 0 511 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:EN-US;}p{mso-style-priority:99;mso-margin-top-alt:auto;margin-right:0cm;mso-margin-bottom-alt:auto;margin-left:0cm;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Times New Roman",serif;mso-fareast-font-family:"Times New Roman";}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:EN-US;}div.WordSection1{page:WordSection1;}