Browsing by Author "Visser, Maria Johanna Elizabeth"

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    Investigating systemic inflammation and hypercoagulability in psoriasis: implications for cardiovascular disease
    (Stellenbosch : Stellenbosch University, 2022-12) Visser, Maria Johanna Elizabeth; Pretorius, Etheresia; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Psoriasis (PsO) is a common immune-mediated inflammatory disease of the skin, typically presenting as erythematous plaques covered with silvery scales. The condition is of multifactorial aetiology, encompassing interactions between environmental factors, genetic susceptibility, and dysregulated immune responses. The pathogenesis of PsO is predominantly driven by interleukin (IL)-17. In addition, inflammatory mediators associated with T helper (TH) 1, TH17, and TH22 subsets are also overexpressed in psoriatic skin. Moreover, these inflammatory molecules may also be detected in the systemic circulation of patients with PsO. The disease is not solely limited to cutaneous sites, as multiple comorbidities have been linked to the condition. Notably, patients with PsO have been reported to have a significantly increased risk of cardiovascular disease (CVD). A potential mechanism that might contribute to this association is the presence of a hypercoagulable state – driven by persistent systemic inflammation – in these individuals. A pro-inflammatory milieu may favour coagulation, while suppressing natural anticoagulant mechanisms. In addition, inflammation may also alter – albeit indirectly – the fibrin clot structure and, by extension, the properties of the fibrin network. Therefore, the aim of this study was to assess the haemostatic profile and investigate potential alterations in fibrin clot structure in patients with PsO, compared to healthy individuals. Whole blood samples were collected from patients with PsO (n=20) and healthy control subjects (n=20). The concentrations of blood-based markers of inflammation and endothelial and platelet activation were determined using enzyme-linked immunosorbent assays. Coagulation status was assessed by thromboelastography. The fibrin network architecture was analysed by scanning electron microscopy. Fibrin secondary structure was assessed through the examination of formalin-fixed, paraffin-embedded plasma clot sections using fluorescence microscopy and Fourier transform infrared (FTIR) spectroscopy. In order to detect areas rich in β-sheet structures, Congo red staining was performed, and sections were examined with brightfield and fluorescence microscopy. To determine if there were quantitative differences in the distribution of specific secondary structural elements in fibrin clots, FTIR analysis was conducted. Elevated levels of inflammatory molecules (C-reactive protein, serum amyloid A, soluble intercellular adhesion molecule-1, and soluble P-selectin) were associated with PsO, thereby confirming the presence of systemic inflammation in patients with PsO. Thromboelastographic analysis revealed an increased tendency towards clot formation, that was also associated with disease presence. Moreover, the ultrastructure of fibrin clots from patients with PsO was altered – these clots were denser and consisted of thicker fibrin fibres, as compared to control subjects. Regarding the secondary structure of fibrin, the presence of β-sheet-rich areas, as identified by Congo red fluorescence, was detected in fibrin clots from both groups. Accordingly, FTIR analysis also did not show any significant differences between the secondary structure composition of fibrin clots from patients with PsO and those of healthy control subjects. Taken together, the results of this study indicate that a hypercoagulable state is present in patients with PsO. This hypercoagulability seems to be a result of persistent systemic inflammation, rather than alterations to the molecular structure of fibrin. The hypercoagulable state in PsO might have implications for the management of CVD risk for individuals living with the condition.