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Chymotrypsin-Like Protease (Chymase) Mediates Endothelial Activation by Factors Derived From Preeclamptic Placentas

Department of Obstetrics and Gynecology, Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center, Shreveport, Louisiana

Chang Liu, BS

Department of Obstetrics and Gynecology, Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center, Shreveport, Louisiana

J. Steven Alexander, PhD

Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center, Shreveport, Louisiana

Lynn J. Groome, MD, PhD

Department of Obstetrics and Gynecology, Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center, Shreveport, Louisiana

Yuping Wang, MD, PhD

Department of Obstetrics and Gynecology, Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center, Shreveport, Louisiana, ywang1{at}lsuhsc.edu

Endothelial cells (EC) activation is an important inflammatory phenotypic change in the vascular system in women with preeclampsia (PE). In PE, maternal vessel chymotrypsin-like protease (CLP)/chymase expression was increased. Chymase is an inflammatory protease. In this study, we specifically examined whether placental-derived CLP could induce EC activation and whether EC activation is associated with increased cellular protease expression. Human uterine microvascular endothelial cells (UtMVECs) were used. Endothelial activation was determined by endothelial adhesion molecule P-selectin, E-selectin, inter-cellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) expressions and by extracellular regulated kinase (ERK) activity. Activation of endogenous CLP/chymase associated with ERK phosphorylation was further examined by CLP/chymase short interfering RNA (siRNA). Our results showed that cells treated with PE placental conditioned medium revealed increased P-selectin, E-selectin, and VCAM-1 expressions and increased ERK phosphorylation. Increased endothelial adhesion molecule expression and phosphorylated ERK (pERK) induction could be attenuated or abolished by depletion of CLP in the conditioned medium or by transfecting ECs with CLP/chymase siRNA. These observations suggest that placental-derived CLP/chymase is responsible for inducing endothelial inflammatory phenotypic changes possibly by upregulation of cell adhesion molecule expressions, activation of cellular protease, and induction of ERK phosphorylation. We speculate that activation of endothelial CLP/chymase may directly relate to the increased inflammatory phenotypic changes in the vascular system in women with PE.

Key Words: Endothelial activation • adhesion molecules • CLP/chymase • preeclampsia.

This version was published on September 1, 2009

Reproductive Sciences, Vol. 16, No. 9, 905-913 (2009)
DOI: 10.1177/1933719109337333


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