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INVESTIGATING THE UNDERLYING MECHANISMS OF INCREASED BLOOD PRESSURE IN A POSTMENOPAUSAL RHEUMATOID ARTHRITIS (RA) RAT MODEL

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dc.contributor.authorNAVISHAA GOVINDASAMY
dc.date.accessioned2023-10-06T15:32:01Z
dc.date.available2023-10-06T15:32:01Z
dc.date.issued2022
dc.description.abstractMenopause and rheumatoid arthritis (RA) are both known to cause elevation of blood pressure in women, and it is known that RA is more prevalent in women around menopausal age. However, the mechanism of elevated blood pressure in postmenopausal RA women is not known. Thus, the aim of this study was to identify the underlying mechanisms of increased blood pressure in ovariectomised RA rat models. Rats were randomly divided into six groups: sham, ovariectomised (Ovx), RA induced ovariectomised (Ovx+RA), and RA induced ovariectomised plus 17 β-oestradiol, baricitinib or losartan. Blood pressure was measured through carotid artery cannulation. Haematoxylin and Eosin (H&E) and Picro Sirius Red staining was performed on the aorta and heart tissues to evaluate histological alterations and collagen deposition. Immunohistochemistry, immunofluorescence and qPCR methods were used to evaluate the oxidative, inflammatory, growth and fibrosis, and apoptosis markers in the aorta and heart tissues. Mean arterial pressure (MAP) was significantly raised in the Ovx rats compared to sham rats and slightly raised without significant difference in the Ovx+RA rats compared to Ovx rats. MAP in the RA induced ovariectomised rats were significantly reduced with 17 β-oestradiol and losartan treatment. H&E and Picro Sirius staining revealed enhanced collagen deposition in the aorta and heart tissues and increased fibrosis in the heart tissue of the Ovx+RA rats. The collagen deposition and fibrosis were reduced with 17 β-oestradiol treatment. Immunohistochemistry, immunofluorescence and qPCR studies revealed that Ovx+RA rats had elevated expression of oxidative markers such as endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), NADPH oxidase 2 (Nox2) and NADPH oxidase 4 (Nox4), inflammatory markers such as toll-like receptor 4 (TLR4) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), growth and fibrosis marker such as vascular endothelial growth factor (VEGF), and apoptosis marker such as caspase-3 in the aorta and heart tissues. The expressions of these markers were reduced with 17 β-oestradiol treatment. In conclusion, the findings from the RA induced ovariectomised rat models suggest that hypertension in postmenopausal RA women occurs due to enhanced oxidative stress, inflammation, fibrosis and apoptosis; and oestrogen treatment could reduce the blood pressure in postmenopausal RA women by inhibiting these mechanisms.en_US
dc.identifier.urihttps://hdl.handle.net/20.500.14377/32199
dc.language.isoenen_US
dc.publisherInternational Medical Universityen_US
dc.subjectMenopauseen_US
dc.subjectArthritis, Rheumatoiden_US
dc.subjectBlood Pressureen_US
dc.subjectWomenen_US
dc.subjectOxidative Stressen_US
dc.subjectInflammationen_US
dc.subjectFibrosisen_US
dc.titleINVESTIGATING THE UNDERLYING MECHANISMS OF INCREASED BLOOD PRESSURE IN A POSTMENOPAUSAL RHEUMATOID ARTHRITIS (RA) RAT MODELen_US
dc.typeThesis
dspace.entity.typePublication
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