Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428091
Title: Infection and early vascular disease in childhood
Author: Charakida, Marietta
ISNI:       0000 0001 3529 4924
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2006
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Abstract:
Endothelial dysfunction and inflammation are thought to be key events in the initiation and progression of atherosclerosis. Infection is one of the most common inflammatory stimuli. This thesis sought to evaluate methods for clinical assessment of vascular dysfunction in the young and explored the impact of infection and its modifiers on pre-clinical arterial disease. The reproducibility of three non-invasive methods known to measure nitric oxide mediated endothelial function was assessed in children and young adults. Of the three methods FMD appeared the most reproducible in our hands especially in children. In addition both FMD and pulse wave analysis following salbutamol inhalation were sensitive to detect acute endothelial changes induced by an extrinsic inflammatory stimulus, typhoid vaccination. The impact of acute common infections and chronic HIV infection on endothelial function and structure was assessed. Acute infections resulted in endothelial dysfunction, which subsequently recovered to normal. In contrast, chronic HIV infection in children was associated with more pronounced long-term functional and structural arterial changes. These abnormalities were more evident in children receiving antiretroviral treatment and those with a history of more advanced HIV disease. Host modulators of the vascular response to infection were studied by investigating the role of mannose binding lectin (MBL). Children with allelic variations of the MBL gene, consistent with low MBL levels, had aggravated endothelial response to acute infection. In vitro work demonstrated the key role of MBL as a modulator of the inflammatory response to specific infectious stimuli. This work provides evidence that infection may act as an important mediator of vascular dysfunction in early life and that endogenous factors that alter the host response to infection have potential to modify the effect of infection at a vascular level.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.428091  DOI: Not available
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