This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 51/2/554    most recent HYPERTENSIONAHA.107.102905v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hering, L. Articles by Dechend, R. Search for Related Content PubMed PubMed Citation Articles by Hering, L. Articles by Dechend, R. Related Collections Animal models of human disease Pathophysiology Other hypertension Smooth muscle proliferation and differentiation

(Hypertension. 2008;51:554.)
© 2008 American Heart Association, Inc.

Original Articles Part 2

Trophoblasts Reduce the Vascular Smooth Muscle Cell Proatherogenic Response

Lydia Hering; Florian Herse; Stefan Verlohren; Joon-Keun Park; Maren Wellner; Fatimunnisa Qadri; Robert Pijnenborg; Anne C. Staff; Berthold Huppertz; Dominik N. Muller; Friedrich C. Luft; Ralf Dechend

From the Experimental and Clinical Research Center (L.H., S.V., F.Q., D.N.M., F.C.L.), Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; Medical Faculty of the Charité (F.H., M.W., F.C.L., R.D.), Franz-Volhard Clinic, HELIOS Clinic, Berlin, Germany; Department of Obstetrics (S.V.), Charité University Medicine, Berlin, Germany; Medical School of Hannover (J-K.P.), Hannover, Germany; Department of Obstetrics and Gynaecology (R.P.), University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Obstetrics and Gynecology (A.C.S.), Ulleval University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway; and the Institute of Cell Biology, Histology, and Embryology (B.H.), Center of Molecular Medicine, Medical University Graz, Graz, Austria.

Correspondence to Ralf Dechend, HELIOS Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125 Berlin, Germany. E-mail ralf.dechend{at}charite.de

Maternal spiral artery remodeling is the consequence of controlled trophoblast invasive interaction with the maternal cellular environment and is fundamentally important for successful placentation. In preeclampsia, trophoblast invasion is shallow, remodeling is incomplete, and vessels develop an inflammatory appearance, termed "acute atherosis." We noted that, in our preeclampsia, human renin-human angiotensinogen transgenic rat model, complement component 3 (C3), and tumor necrosis factor- were upregulated and heavily expressed in atherotic uteroplacental vessels. We next used coculture involving human trophoblasts, rat vascular smooth muscle cells (VSMCs), and human VSMCs to observe VSMC-trophoblast regulatory interactions. Tumor necrosis factor- induced complement C3 and interleukin-6 expression in VSMCs. We found that trophoblasts were able to reduce VSMC C3 and interleukin-6 expression after the VSMCs were stimulated with tumor necrosis factor-. However, a direct VSMC-trophoblast cell-cell contact was necessary for this anti-inflammatory response. We also studied double-transgenic VSMCs that express inflammatory components and exhibit accelerated proliferation ("synthetic" phenotype). Trophoblasts could not downregulate C3 in these cells. We then examined uteroplacental tissues from preeclamptic and control patients. In control deciduas, only traces of C3 staining were observed, and vessels were thin walled without thrombus formation. In preeclampsia, the decidual vessels showed atherosis, thrombus formation, and C3 expression. Our data suggest that fetally derived trophoblasts require direct cell-cell contact with maternally derived VSMCs to downregulate VSMC C3 and interleukin-6 expression and to avoid atherosis. The findings also implicate C3 in the placental vasculopathy observed in preeclampsia.

Key Words: vascular remodeling • complement • preeclampsia • trophoblast • acute atherosis