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

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

1. Keiichi Kumasawaa,b,1,
2. Masahito Ikawaa,1,2,
3. Hiroyasu Kidoyac,
4. Hidetoshi Hasuwaa,
5. Tomoko Saito-Fujitaa,3,
6. Yuka Moriokaa,4,
7. Nobuyuki Takakurac,
8. Tadashi Kimurab, and
9. Masaru Okabea

+ Author Affiliations

1. Departments of aExperimental Genome Research and
2. cSignal Transduction, Research Institute for Microbial Diseases, and
3. bDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan

* ↵3Present address: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
* ↵4Present address: Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.

1. Edited by R. Michael Roberts, University of Missouri, Columbia, MO, and approved November 19, 2010 (received for review August 5, 2010)
2. ↵1K.K. and M.I. contributed equally to this work.

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.

* 3-hydroxy-3-methyl-glutaryl-CoA
* hemolytic anemia, elevated liver enzymes, and low platelet count
* trophoblast

Footnotes

* 2To whom correspondence should be addressed. E-mail: ikawa@biken.osaka-u.ac.jp.
* Author contributions: K.K., M.I., T.K., and M.O. designed research; K.K., M.I., H.K., H.H., T.S.-F., and Y.M. performed research; M.I. and H.K. contributed new reagents/analytic tools; K.K., M.I., N.T., T.K., and M.O. analyzed data; and K.K., M.I., T.K., and M.O. wrote the paper.
* The authors declare no conflict of interest.
* This article is a PNAS Direct Submission.
* This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1011293108/-/DCSupplemental.

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




GINECOLOGÍA
Actualidad Ultimas noticias - JANOes -
Estatinas para tratar la preeclampsia

JANO.es · 18 Enero 2011 09:46

Aunque no se recomiendan en el primer trimestre de embarazo, un equipo japonés de investigadores apunta que el uso vigilado del fármaco podría ser muy eficaz para tratar la preeclampsia.


Un equipo de investigadores de la University of Osaka, Japón, propone utilizar una estatina para tratar la preeclampsia, un tratamiento utilizado en muchos pacientes para combatir el colesterol.

En experimentos con ratones, publicados en la revista Proceedings of the National Academy of Sciences (PNAS), este tipo de fármaco demostró su capacidad para reducir al mínimo los síntomas de la preeclampsia (hipertensión y presencia de proteínas en la orina, entre otros).

En los experimentos con ratones gestantes, no se observó ningún daño ni deformidad en los fetos y, aunque no se recomienda utilizar el fármaco en el primer trimestre, los investigadores creen que en el futuro no habría riesgos para el feto si se decide utilizar en tratamientos con mujeres embarazadas. De esta manera, los científicos creen que el uso vigilado de estatinas en el tratamiento de la preeclampsia podría ser muy eficaz.


Proceedings of the National Academy of Sciences 2010;doi:10.1073/pnas.1011293108
Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model — PNAS

Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences

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