An evaluation of the role of platelet activation in HIV-related cardiovascular diseases onset

Dominick, Leanne Lynn (2021-03)

Thesis (MSc)--Stellenbosch University, 2021.

Thesis

ENGLISH ABSTRACT: Background: Although combined anti-retroviral treatment (cART) lowered HIV-AIDS onset, HIVpositive individuals display increased cardiovascular disease (CVD) onset. Enhanced myocardial fibrosis has emerged as a crucial mediator of HIV-induced heart failure (HF). This study hypothesized that in HIV-infection there is immune dysregulation that can trigger persistent platelet activation and the release of mediators, which contributes to an increased risk of CVD. Markers of platelet activation were investigated in a South African population. These parameters were correlated with clinical tests of cardiac function (blood pressure [BP], electrocardiogram [ECG] and flow-mediated dilation [FMD]), markers of disease progression (CD4 and viral load) and a pro-fibrotic marker transforming growth factor-β [TGF-β]. Aim: The aim of this study was to investigate platelet activation through the expression of platelet activation markers in HIV-positive individuals and its association with CVD. Methods: Thirty-six male and female participants between the ages of 18-55 years were recruited at People’s Healthcare clinic in Worcester in the Western Cape province: n=13 HIV-negative, n=23 HIV-positive on cART. Patients with tuberculosis co-infection and pregnancy formed part of the exclusion criteria and were excluded from this study. Medical history and lifestyle questionnaires were completed while BP, ECG and FMD readings were recorded. Fasted blood samples were collected by a registered research nurse. Flow cytometry was conducted to evaluate platelet activation markers, such as CD62P, latent associating protein (LAP), glycoprotein A-repetitions predominant (GARP) and TGF-β. Results: Our results showed a significant lower systolic and diastolic BP amongst HIV-positive patients, p<0.0001 and p<0.05, respectively. This displayed a moderate, negative correlation with platelet activation markers, such as CD62P and LAP (p<0.05). GARP exhibited significant, positive correlations with diastolic BP (p<0.05), TGF-β (p<0.0001) and viral load (p<0.05). Additionally, a significantly lower FMD (p<0.05) with shorter QT interval was also observed in HIV-positive patients/subjects (p<0.05). Conclusion: The major findings of this study for HIV-positive individuals are: a) the observation of lower BP (systolic and diastolic), b) GARP upregulation and its strong correlation with disease progression (CD4 and viral load) and fibrosis (TGF-β) markers, c) the identification of a moderate negative association between platelet activation markers and BP, d) lower FMD and e) shorter QT intervals. We propose that these factors contribute to an increased risk of HF/CVD in HIV-positive individuals. Our findings warrant future investigation to elucidate the exact role of platelet activation and the risk of HF/CVD in PLHIV, especially in SSA.

AFRIKAANSE OPSOMMING: Agtergrond: Alhoewel gekombineerde anti-retrovirale behandeling (kARK) die aanvang van MIV-VIGS verlaag het, vertoon MIV-positiewe individue ‘n verhoogde risiko van kardiovaskulêre siektes (KVS). Miokardiale fibrose kom voor as 'n belangrike faktor van MIV-geïnduseerde hartversaking. Hierdie studie hipoteseer dat daar immuunstelselregulering in MIV-positiewe individue is wat aanhoudende bloedplaatjie-aktivering en die vrystelling van bemiddelaars kan veroorsaak, en bydra tot 'n verhoogde risiko van KVS. Merkers van bloedplaatjie-aktivering in 'n Suid-Afrikaanse MIV-positiewe groep is ondersoek. Hierdie parameters korreleer met kliniese toetse van hartfunksie (bloeddruk (BD), elektrokardiogram (EKG),vloei-gemedieerde dilatasie (VGD)), merkers van siekteprogressie (CD4 en virale lading) en pro-fibrotiese merker transformerende groeifaktor beta-β (TGF-β). Doelwitte: Die doel van hierdie studie was om bloedplaatjie-aktivering te ondersoek deur die uitdrukking van bloedplaatjie-aktivering merkers in MIV- positiewe individue en die assosiasie met kardiovaskulêre siektes. Metodes: Ses-en-dertig deelnemers tussen die ouderdomme 18-55 jaar is in People’s Healthcare kliniek in Worcester in die Wes-Kaap provinsie gewerf: n = 13 MIV-negatief, n = 23 MIV-positief op kARK. Pasiënte met tuberkulose-infeksie en swangerskap , vorm deel van die uitsluitingskriteria en is nie by die studie ingesluit nie. Mediese geskiedenis en 'n leefstylvraelys is voltooi terwyl BD, EKG en VGD opgeneem is. Bloedmonsters is deur ‘n geregistreerde navorsings verpleegster versamel tydens vas. Vloeisitometrie ontledings is gebruik om plaatjieaktivering merkers,CD62P, latente assosierende proteïen (LAP), glikoproteïen A-herhalings oorheersend (GARP) en TGF-β te evalueer.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/109976
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