Human monocyte subsets in coronary artery disease and myocardial infarction

Tapp, Luke David (2014). Human monocyte subsets in coronary artery disease and myocardial infarction. University of Birmingham. M.D.

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Abstract

Coronary artery disease (CAD) is a disease of inflammatory aetiology, and remains the commonest cause of death globally despite therapeutic advances. Monocytes are implicated in the pathogenesis of CAD, but also in reparative mechanisms after myocardial infarction (MI) due to subset heterogeneity. The aim of this thesis was to provide a detailed phenotypic comparison of differences between the three human monocyte subsets in CAD and after MI, with particular emphasis on CD16+ monocytes which have previously been analysed as a single population rather than two distinct subsets. Longitudinal changes were analysed following MI and relationships explored with plasma cytokines. Multiple significant novel changes in monocyte phenotype attributable to specific subsets were identified, particularly related to the CD14++CD16+CCR2+ ‘Mon2’/‘Intermediate’ subset which increased in number on day 1 after MI and appeared highly functionally active. There were significant changes in expression of a range of receptors associated with inflammation, migration and reparative processes. Significant relations to plasma cytokines and the degree of myocardial damage were observed. Most monocyte parameters predictive of left ventricular ejection fraction six weeks after MI were related to the Mon2 subset. This suggests an important role for this subset in the acute phase of MI.

Type of Work:

Thesis (Higher Doctorates > M.D.)

Award Type:

Higher Doctorates > M.D.

Supervisor(s):