Role of osteocalcin and silencing of apoe as risk markers of worsening metabolic diseases associated with menopause in a study model in murines

Name: Higor Scardini Santana
Type: MSc dissertation
Publication date: 23/06/2020
Advisor:

Namesort descending Role
Leticia Batista Azevedo Rangel Advisor *

Examining board:

Namesort descending Role
Alexandre Martins Costa Santos Internal Examiner *
Leticia Batista Azevedo Rangel Advisor *
Paulo Cilas Morais Lyra Junior External Examiner *

Summary: Menopause is characterized by decreased activity of the ovaries, which occurs gradually and, consequently, leads to a reduction in the production of female sex hormones. Estrogen (E2) influences the most diverse phenomena in the body and, therefore, its absence causes an imbalance in several systems, including the vascular and bone systems. In bone tissue, estrogen is responsible for maintaining bone remodeling (in English turnover), controlling osteoblastic and osteoclastic activity via the RANK, RANK-Ligand and osteoprotegerin proteins. The imbalance of the pathway affects the maturation and apoptosis of osteoblasts, compromising the expression of bone matrix proteins, such as osteocalcin {}. Osteocalcin (OCC) is a 12 kD protein from the gamma carboxylated family (GLA) in glutamic acid residues and responsible for the nucleation of calcium (Ca2 +) in the organic matrix. The presence of OCC in serum, in high concentrations when compared to bone, can often be an indicator of bone mineral loss and osteoporosis. The present study aims to better elucidate the post-menopause effect on bone metabolism and its adjacent complications, evaluating serum concentrations and possible damage to bone, cardiovascular and renal tissue. Using ovariectized animals (OVX) to mimic hormonal depletion and ApoEKO transgenic animals to mimic the effects of the ApoE E4 allele, we carry out the most diverse biochemical dosing techniques in search of profile changes. It is known that the Eda ApoE isoform, of low affinity to the LDL receptor, is associated with a higher risk of osteoporosis and bone fractures in the elderly. Soon the animals submitted to ovariectomy and eventual depletion of these hormones ended up developing symptoms mimetic to osteoporosis, dyslipidemia, atherosclerosis, arteriosclerosis and kidney diseases, corroborating in some data with what literature suggests. The innovation proposed by this work was to verify how the mutation of apolipoprotein E could worsen the condition of the aforementioned diseases, in addition to pointing out osteocalcin as a risk factor for cardiovascular calcification in pre-existing atherosclerotic conditions.

Keywords: Estrogen. Ovariectomy. ApoE. Osteocalcin. Menopause.

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