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The implications of eosinophilia and circulating fibrocytes in HIV-mediated cardiac fibrosis
Thesis (MSc)--Stellenbosch University, 2023.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2023
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| _version_ | 1867613812572553216 |
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| access_status_str | Open Access |
| author | Mfiki, Litha Abigail |
| author2 | Essop, M. Faadiel |
| author_browse | Essop, M. Faadiel Mfiki, Litha Abigail |
| author_facet | Essop, M. Faadiel Mfiki, Litha Abigail |
| author_sort | Mfiki, Litha Abigail |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2023. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/129413 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:42:05.565Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/129413 The implications of eosinophilia and circulating fibrocytes in HIV-mediated cardiac fibrosis Mfiki, Litha Abigail Essop, M. Faadiel Teer, Eman Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. HIV infections -- Complications Heart -- Fibrosis Inflammation -- Pathophysiology Eosinophilia Immune response CD4 antigen HIV (Viruses) -- Immunological aspects Fibroblasts UCTD Thesis (MSc)--Stellenbosch University, 2023. ENGLISH ABSTRACT: The increased global rollout of combination antiretroviral therapy (cART) has decreased acquired immunodeficiency disease (AIDS)-related deaths among the human immunodeficiency virus (HIV)-infected population. However, in parallel, non-communicable diseases such as cardiovascular diseases (CVDs) have become increasingly common in this population. For example, in developing countries, heart failure (HF) and subsequent sudden cardiac death (SCD) are frequently observed in the HIV population, with myocardial fibrosis indicated as a key contributor to HIV-related HF. This study, therefore, aimed to investigate HIV-mediated cardiac fibrosis and the impact of immune dysregulation and chronic inflammation on the persistent activation of innate immunity and hematological abnormalities. We hypothesized that persistent immune cell activation and chronic inflammation stimulate the upregulation of anti-inflammatory and profibrotic cytokines, instigating cardiac fibrosis via fibrocyte activation and other profibrotic pathways. The study population (n = 38), aged between 27-57 years, was recruited for the People's Healthcare Clinic in Worcester, South Africa. They were divided into groups based on their HIV status and CD4 count. The groups were as follows: HIV negative (n = 8), HIV positive (HIV+) with a CD4 count less than 500 cells/mm3 (n = 17), HIV+ with a CD4 count more than 500 cells/mm3 (n = 13), HIV+ with a CD4 count less than 200 cells/mm3 (n = 7), and HIV+ with a CD4 count more than 200 cells/mm3 (n = 23). Blood (fasted) was collected and used to evaluate monocyte/macrophage activation (CD45, CD14, CD16, CD86, CD163) and circulating fibrocyte evaluation (CD45, CD34, COL-1) through flow cytometry. A complete blood count and differential leukocyte count were used to assess for any hematological abnormalities. Our data revealed a significant increase in the expression of CD163 (the M2 macrophage marker) when compared to CD86 (the M1 macrophage marker) (p< 0.0001). An increased expression of CD34+COL-1+ (p = 0.05) and COL-1+ (p = 0.03) circulating fibrocytes was observed in the HIV+ CD4 < 200 cells/mm3 group when compared to the control group. Additionally, 43% of the HIV+ CD4 < 200 cells/mm3 group and 38% of the HIV+ CD4 < 500 cells/mm3 group displayed an eosinophil differential leukocyte count of more than 4%. A robust positive correlation between the differential leukocyte count (of eosinophils) and CD34+COL-1+ fibrocytes (r = 0.52, p = 0.0009) was also observed. The significant discoveries of this study for the HIV+ population are a) the insignificant expansion of non-classical monocytes, b) a higher expression of M2 macrophages compared to M1 macrophages, c)the enhanced expression of COL-1+ fibrocytes and co-expression of CD34+COL-1+ fibrocytes, d) significant eosinophilia, and e) the strong correlation between eosinophils and CD34+COL-1+ fibrocytes. According to these findings, HIV-associated eosinophilia may be initiated by an elevated level of inflammation that results in immune dysregulation, an upregulation of anti-inflammatory and profibrotic responses, and an increased expression of fibrocytes. We propose that these factors may be used as a novel screening technique to identify cardiac fibrosis within the HIV+ population. AFRIKAANSE OPSOMMING: Die verhoogde wêreldwye ontplooiing van kombinasie antiretrovirale terapie (kART) het verworwe immuniteitsgebreksiekte (VIGS)-verwante sterftes onder die menslike immuniteitsgebreksvirus (MIV)-geïnfekteerde bevolking verminder. Terselfdertyd het nie-oordraagbare siektes soos kardiovaskulêre siektes (KVS's) egter toenemend algemeen in hierdie bevolking geword. Byvoorbeeld, in ontwikkelende lande word hartversaking (HV) en daaropvolgende skielike hartdood (SKD) gereeld in die MIV-bevolking waargeneem, met miokardiale fibrose wat as 'n sleutelbydraer tot MIV-verwante HF aangedui word. Hierdie studie het dus ten doel gehad om MIV-gemedieerde kardiale fibrose en die impak van chroniese inflammasie en immuundisregulering in die aanhoudende aktivering van aangebore immuniteit en hematologiese abnormaliteite te ondersoek. Ons het veronderstel dat die aanhoudende aktivering van immuunselle en chroniese inflammasie lei tot die opregulering van anti-inflammatoriese en pro-fibrotiese sitokiene, wat die ontwikkeling van hartfibrose via fibrosietaktivering en ander profibrotiese weë veroorsaak. Die studiepopulasie (n = 38), tussen die ouderdomme van 27-57 jaar, is gewerf vir die People's Healthcare Clinic in Worcester, Suid-Afrika. Hulle is in groepe verdeel op grond van hul MIV-status en CD4-telling. Die groepe was soos volg: MIV-negatief (n = 8), MIV-positief (MIV+) met 'n CD4- telling minder as 500 selle/mm³ (n = 17), MIV+ met 'n CD4-telling meer as 500 selle/mm³ (n = 13), MIV+ met 'n CD4-telling minder as 200 selle/mm³ (n = 7), en MIV+ met 'n CD4-telling meer as 200 selle/mm³ (n = 23). Bloed (vas) is versamel en gebruik om monosiet/makrofage-aktivering (CD45, CD14, CD16, CD86, CD163) en sirkulerende fibrosiete-evaluering (CD45, CD34, COL-1) deur vloeisitometrie te evalueer. 'n Volledige bloedtelling en differensiële leukosiettelling is gebruik om te bepaal vir enige hematologiese abnormaliteite. Ons data het 'n beduidende toename in die uitdrukking van CD163 (M2 makrofaag) getoon in vergelyking met CD86 (M1 makrofaag merker) (p<0.0001). 'n Verhoogde uitdrukking van CD34+COL1+ (p = 0.05) en COL+ (p = 0.03) sirkulerende fibrosiete is waargeneem in die MIV+ CD4 < 200 selle/mm³ groep. Daarbenewens het 43% van die MIV+ CD4 < 200 selle/mm³ groep en 38% van die MIV+ CD4 < 500 selle/mm³ groep 'n eosinofiele differensiële leukosiettelling van meer as 4% getoon. 'n Sterk positiewe korrelasie tussen die differensiële leukosiettelling (van eosinofiele) en CD34+COL1+ fibrosiete (r = 0,52 p = 0,0009) is ook waargeneem. Die betekenisvolle ontdekkings van hierdie studie vir die MIV+ populasie is a) die onbeduidende uitbreiding van nie-klassieke monosiete, b) 'n hoër uitdrukking van M2 makrofage in vergelyking met M1 makrofage, c) die verhoogde uitdrukking van COL-1+ fibrosiete en mede-uitdrukking van CD34+COL-1+fibrosiete, d) beduidende eosinofilie, en e) die sterk korrelasie tussen eosinofiele en CD34+COL-1+ fibrosiete. Volgens hierdie bevindinge kan MIV-geassosieerde eosinofilie geïnisieer word deur 'n verhoogde vlak van inflammasie wat lei tot immuundisregulering, 'n opregulering van anti-inflammatoriese en pro-fibrotiese response, en 'n verhoogde uitdrukking van fibrosiete. Ons stel voor dat hierdie faktore as 'n nuwe siftingstegniek gebruik kan word om kardiale fibrose binne die MIV+ populasie te identifiseer. Masters 2023-11-23T15:55:56Z 2024-02-20T10:43:24Z 2023-11-23T15:55:56Z 2024-02-20T10:43:24Z 2023-12 Thesis https://scholar.sun.ac.za/handle/10019.1/129413 en Stellenbosch University xvii, 116 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | HIV infections -- Complications Heart -- Fibrosis Inflammation -- Pathophysiology Eosinophilia Immune response CD4 antigen HIV (Viruses) -- Immunological aspects Fibroblasts UCTD Mfiki, Litha Abigail The implications of eosinophilia and circulating fibrocytes in HIV-mediated cardiac fibrosis |
| title | The implications of eosinophilia and circulating fibrocytes in HIV-mediated cardiac fibrosis |
| title_full | The implications of eosinophilia and circulating fibrocytes in HIV-mediated cardiac fibrosis |
| title_fullStr | The implications of eosinophilia and circulating fibrocytes in HIV-mediated cardiac fibrosis |
| title_full_unstemmed | The implications of eosinophilia and circulating fibrocytes in HIV-mediated cardiac fibrosis |
| title_short | The implications of eosinophilia and circulating fibrocytes in HIV-mediated cardiac fibrosis |
| title_sort | implications of eosinophilia and circulating fibrocytes in hiv mediated cardiac fibrosis |
| topic | HIV infections -- Complications Heart -- Fibrosis Inflammation -- Pathophysiology Eosinophilia Immune response CD4 antigen HIV (Viruses) -- Immunological aspects Fibroblasts UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/129413 |
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