Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
Exploring mechanisms underlying stress-related cardiometabolic complications
Thesis (MSc)--Stellenbosch University, 2022.
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | en_ZA |
| Published: |
Stellenbosch : Stellenbosch University
2022
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613917849583616 |
|---|---|
| access_status_str | Open Access |
| author | Cairns, Megan Louise |
| author2 | Essop, M. Faadiel |
| author_browse | Cairns, Megan Louise Essop, M. Faadiel |
| author_facet | Essop, M. Faadiel Cairns, Megan Louise |
| author_sort | Cairns, Megan Louise |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/125123 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:43:46.104Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/125123 Exploring mechanisms underlying stress-related cardiometabolic complications Cairns, Megan Louise Essop, M. Faadiel Joseph, Danzil Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Cardiometabolic diseases Cardiovascular system -- Diseases -- Risk factors Oxidative stress -- Animal models Wistar rats -- Physiology UCTD Thesis (MSc)--Stellenbosch University, 2022. ENGLISH ABSTRACT: Introduction: Cardiometabolic diseases (CMD) constitute a major, global burden of disease. Of concern, psychosocial stress is an emerging risk factor for cardiovascular diseases onset. Although associations between psychological complications and CMD are well established, the underlying mechanisms driving this process require further investigation. Oxidative stress is linked to both chronic stress and CMD progression and can elicit detrimental sequelae. For example, it can augment PARP activity and thereby shunt glycolytic intermediates into the hexosamine biosynthetic pathway (HBP). Increased HBP flux can in turn lead to dysregulated O-GlcNAcylation of target proteins, thereby potentiating cardiometabolic complications. As excessive HBP flux is observed in a range of CMD, we hypothesized that increased oxidative stress and HBP activation play a key role in stress-mediated CMD onset and progression. Our main objective was to assess the degree of total protein O-GlcNAcylation and redox status of cardiac tissues isolated from stressed versus control rats. Methods: This preclinical study exposed male Wistar rats (n = 14 per group) to 9.5 weeks of unpredictable chronic mild stressors versus non-stressed controls. Behavioral tests were initially conducted to assess the presence of depression and anxiety. Post- euthanasia, plasma corticosterone, and epinephrine levels were evaluated, while myocardial redox state, glucocorticoid receptor expression, and activity, as well as HBP activation, were also determined. Results: Stressed rats displayed an anxious phenotype, with lowered plasma corticosterone levels (p = 0.0394 vs. controls) and higher plasma epinephrine concentrations (p = 0.0284 vs. controls). Our data revealed increased cardiac lipid peroxidation (p = 0.0421 vs. controls) but without any alterations in antioxidant defense systems (catalase, total glutathione, and oxygen radical absorbance capacity). Cardiac HBP activation remained unchanged between the experimental groups, with no significant alterations to GFAT1 or O-GlcNAc expression. Conclusion: These data show that the stress protocol triggered an anxious phenotype together with increased myocardial oxidative stress. The elevated oxidative stress may likely occur as a result of increased reactive oxygen species production instead of an impaired antioxidant system. The HBP data suggest that the mild degree of oxidative damage in the heart was insufficient to alter normal glucose metabolism. AFRIKAANSE OPSOMMING: Inleiding: Kardiometaboliese siektes (KMS) vorm 'n groot, wêreldwye siektelas. Dit is kommerwekkend dat psigososiale stres 'n ontluikende risikofaktor vir die aanvang van kardiovaskulêresiekte is. Hoewel die assosiasie tussen sielkundige komplikasies en KMS goed gevestig is, benodig die onderliggende meganismes wat hierdie proses aandryf, verdere ondersoek. Oksidatiewe stres is gekoppel aan beide chroniese stres en KMS-vordering en kan nadelige gevolge ontlok. Dit kan byvoorbeeld PARP- aktiwiteit versterk en sodoende omleiding van glikolitiese intermediêre na die heksosamien biosintetiese weg (HBW) veroorsaak. Verhoogde HBW-fluks kan dan lei tot wanregulering van O-GlcNAsilering van teikenproteïene en sal sodoende kardiometaboliese komplikasies versterk. Oormatige HBW-fluks word in ‘n verskeidenheid KMS waargeneem en ons hipotiseer dus dat verhoogde oksidatiewe stres en HBW-aktivering 'n sleutelrol in stresgemedieerde KMS-aanvang en vordering speel. Ons hoofdoelwit was om die graad van totale proteïen O-GlcNAsilering en redoksstatus van hartweefsels, geïsoleer vanaf gestresde versus kontrole rotte, te evalueer. Metodes: Hierdie prekliniese studie het manlike Wistar-rotte (n = 14 per group) aan 9.5 weke van onvoorspelbare chroniese ligte stressors blootgestel versus nie- gestresde kontroles. Gedragstoetse is aanvanklik uitgevoer om die teenwoordigheid van depressie en angs te evalueer. Na genadedood is plasmakortikosteroon en epinefrienvlakke geëvalueer, terwyl miokardiale redokstoestand, uitdrukking en aktiwiteit van glukokortikoïedreseptor, sowel as HBW-aktivering, ook bepaal is. Resultate: Gestresde rotte het 'n angstige fenotipe vertoon, met verlaagde plasmakortikosteroonvlakke (p = 0.0394 vs. kontroles) en hoër plasma-epinefrien konsentrasies (p = 0.0284 vs. kontroles). Ons data het verhoogde hartlipiedperoksidasie (p = 0.0421 vs. kontroles) onthul, maar sonder enige veranderinge in antioksidant verdedigingstelsels (katalase, totale glutatioon, en suurstof radikaal absorpsiekapasiteit). HBW-aktivering van die hart was onveranderd tussen die eksperimentele groepe, met geen beduidende veranderinge aan GFAT1- of O-GlcNAc-uitdrukking nie. Gevolgtrekking: Hierdie data toon dat die stresprotokol 'n angstige fenotipe tesame met verhoogde miokardiale oksidatiewe stres veroorsaak het. Die verhoogde oksidatiewe stres mag moontlik weens verhoogde produksie van reaktiewe suurstofspesies voorkom in plaas van 'n verswakte antioksidantstelsel. Die HBW-data dui daarop dat die matige graad van oksidatiewe skade in die hart onvoldoende was om normale glukosemetabolisme te verander. Masters 2022-02-11T05:17:32Z 2022-04-29T12:54:58Z 2023-01-04T03:00:11Z 2022-03 Thesis http://hdl.handle.net/10019.1/125123 en_ZA Stellenbosch University xiv, 153 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Cardiometabolic diseases Cardiovascular system -- Diseases -- Risk factors Oxidative stress -- Animal models Wistar rats -- Physiology UCTD Cairns, Megan Louise Exploring mechanisms underlying stress-related cardiometabolic complications |
| title | Exploring mechanisms underlying stress-related cardiometabolic complications |
| title_full | Exploring mechanisms underlying stress-related cardiometabolic complications |
| title_fullStr | Exploring mechanisms underlying stress-related cardiometabolic complications |
| title_full_unstemmed | Exploring mechanisms underlying stress-related cardiometabolic complications |
| title_short | Exploring mechanisms underlying stress-related cardiometabolic complications |
| title_sort | exploring mechanisms underlying stress related cardiometabolic complications |
| topic | Cardiometabolic diseases Cardiovascular system -- Diseases -- Risk factors Oxidative stress -- Animal models Wistar rats -- Physiology UCTD |
| url | http://hdl.handle.net/10019.1/125123 |
| work_keys_str_mv | AT cairnsmeganlouise exploringmechanismsunderlyingstressrelatedcardiometaboliccomplications |