Background
Women are protected from heart disease early in their lives, which is thought to be due to the female sex hormone estrogen. Estrogen is known to reduce maladaptive growth and stiffening of the heart, as well as to regulate blood pressure, all of which are protective of the heart's healthy function. However, the molecular mechanisms behind this protection are largely unknown.
Estrogen is mainly produced by the ovaries before being secreted into the blood, where it travels to various organs. Estrogen then enters the cells of the heart, binding to estrogen receptors. This estrogen-receptor unit is then able to induce positive and protective changes to the various cells within the heart by altering protein levels and gene expression. A point of change for this protective mechanism is during menopause, when estrogen levels reduce, and the protection is somewhat lost.
Aim of project:
The project will investigate what happens to estrogen and its intracellular signaling on a molecular level, before and after menopause. The project will use hearts from intact and ovariectomized (surgical removal of the ovaries) rats to model pre- and postmenopausal states. Hearts from these rats have been single-nuclei sequenced, and the top hits from this sequencing will be further analyzed in the tissue during this project (tissue already collected). The heart tissue will be analyzed by Western blotting to look at differences in protein levels and qPCR to investigate changes in gene expression at the two stages. Changes in stiffness within the heart will also be investigated with Masson`s trichrome.
The project aims to better understand which genes and proteins are altered by estrogen, with the long-term goal of targeting these genes/proteins for therapy.
If you're interested in this project, please contact main supervisor: Thea Paarsberg Støle t.p.stole@medisin.uio.no
Other supervisors: Cathringe Carlson (co-supervisor) and Pål Falnes (internal supervisor)