Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model

Keiichi Kumasawa, Masahito Ikawa, Hiroyasu Kidoya, Hidetoshi Hasuwa, Tomoko Saito-Fujita, Yuka Morioka, Nobuyuki Takakura, Tadashi Kimura, Masaru Okabe

Research output: Contribution to journalArticle

201 Citations (Scopus)

Abstract

Preeclampsia is a relatively common pregnancy-related disorder. Both maternal and fetal lives will be endangered if it proceeds unabated. Recently, the placenta-derived anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG), have attracted attention in the progression of preeclampsia. Here, we established a unique experimental model to test the role of sFLT1 in preeclampsia using a lentiviral vector-mediated placenta-specific expression system. The model mice showed hypertension and proteinuria during pregnancy, and the symptoms regressed after parturition. Intrauterine growth restriction was also observed. We further showed that pravastatin induced the VEGF-like angiogenic factor placental growth factor (PGF) and ameliorated the symptoms. We conclude that our experimental preeclamptic murine model phenocopies the human case, and the model identifies low-dose statins and PGF as candidates for preeclampsia treatment.

Original languageEnglish
Pages (from-to)1451-1455
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number4
DOIs
Publication statusPublished - 2011 Jan 25
Externally publishedYes

Fingerprint

Pravastatin
Pre-Eclampsia
Intercellular Signaling Peptides and Proteins
Vascular Endothelial Growth Factor Receptor-1
Angiogenesis Inducing Agents
Placenta
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pregnancy
Proteinuria
Vascular Endothelial Growth Factor A
Theoretical Models
Mothers
Parturition
Hypertension
Growth

Keywords

  • 3-hydroxy-3-methyl-glutaryl-CoA
  • Hemolytic anemia, elevated liver enzymes, and low platelet count
  • Trophoblast

ASJC Scopus subject areas

  • General

Cite this

Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model. / Kumasawa, Keiichi; Ikawa, Masahito; Kidoya, Hiroyasu; Hasuwa, Hidetoshi; Saito-Fujita, Tomoko; Morioka, Yuka; Takakura, Nobuyuki; Kimura, Tadashi; Okabe, Masaru.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 4, 25.01.2011, p. 1451-1455.

Research output: Contribution to journalArticle

Kumasawa, Keiichi ; Ikawa, Masahito ; Kidoya, Hiroyasu ; Hasuwa, Hidetoshi ; Saito-Fujita, Tomoko ; Morioka, Yuka ; Takakura, Nobuyuki ; Kimura, Tadashi ; Okabe, Masaru. / Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 4. pp. 1451-1455.
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