miRNA-452 in Patients With Preeclampsia and Its Correlation With MMP-9
Condition: Preeclampsia
MeSH terms: Pre-Eclampsia
Study type: Observational

Summary: 
      Preeclampsia is a pregnancy related disease characterized by the new onset of hypertension
      and proteinuria after 20 weeks of gestation in previously normotensive women. PE is one of
      the most challenging diseases in obstetrics worldwide that affects 2-8 % of pregnancies
      causing both morbidity and mortality of both mother and fetus.
    

Detailed description: 
      The etiology and pathophysiology of preeclampsia are still unclear but the impaired invasive
      ability of the trophoblast cells of the placenta and vascular endothelial cell damage are the
      main two factors. The invasiveness of trophoblast cells depends on the production of
      proteases, particularly matrix metalloproteinases (MMP). MMPs are a family of 24 zinc
      dependent endopeptidases capable of degrading extra cellular matrix components. MMP-9 plays
      an important role in placental invasion and implantation.

      MicroRNAs (miRs) are a class of small (19-24 nucleotides in length), single-stranded,
      non-protein-coding RNAs, which suppress translation or promote the degradation of target
      messenger RNAs (mRNAs) and thus play an important role in the regulation of cell
      proliferation, differentiation, apoptosis and even development of cancer.

      The role of miRNA in preeclampsia pathogenesis has been investigated in a number of studies.
      One of the target areas of the miRNAs that forms a link with preeclampsia pathogenesis is the
      dysregulation of trophoblast differentiation, proliferation, and invasion; this occurs during
      early pregnancy and leads to the development of preeclampsia; a range of miRNAs have been
      confirmed to play pivotal roles in these processes by targeting a number of different genes.

      MiR-452 is a newly discovered cancer related type of miRNA that was shown to be involved in
      invasion process where it was upregulated in certain types of cancer such as blad¬der cancer,
      urothelial carcinoma, and hepatocellular carcinoma and was found to be significantly
      decreased in other types of cancer such as non-small cell lung cancer , glioma, prostate
      cancer and Gastric cell cancer.

      Based on these previous studies which demonstrate the effect of miR-452 in invasion process
      of cancer cells either by stimulation or inhibition and that preeclampsia is a disease of
      impaired placental invasion in which MMP-9 play an important role, we will investigate the
      placental tissues expression changes of miR-452 which is not studied yet in early onset
      preeclampsia patients compared to control and try to find a possible mechanism by which it
      act on placental invasion by measuring expression level of MMP-9 and making correlation
      between them. The results of this study will provide experimental and theo¬retical basis for
      clinical prediction, prevention and treatment of preeclampsia.
    

Intervention name(s): real time PCR (rPCR)
Intervention type(s): Genetic
Intervention description(s): A villus tissue (2.5 cm * 2.5 cm * 2.5 cm) will be cut off immediately from the center of placenta, avoiding the area of infarction, bleeding or calcification. After being washed with normal saline, the tissue will be preserved in liquid nitro¬gen at once for subsequent detection of miR-452 and MMP-9 expression by real time PCR (r-PCR). During this procedure total RNA will be extracted including miR-452 and mRNA of MMP-9. Then by reverse transcriptase RNA will be converted into DNA which will be amplification during the PCR, i.e. in real-time, and not at its end, as in conventional PCR. Expression of miR-452 and MMP-9 will be estimated and correlated with each other.
Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Pregnant women who come for termination of pregnancy by vaginal delivery or CS between
        28-34 weaks gestational age in Assiut university maternity hospital in the age range of
        18-40 years.