Abstract
BackgroundAtherosclerotic lesions are comprised of distinct regions with different proteomic profiles. Men and women develop differences in lesion phenotype, with lesions from women generally being more stable and less prone to rupture. We aimed to investigate the differences in proteomic profiles between sexes, including distinct lesion regions, to identify altered proteins that contribute to these differences observed clinically.MethodsCarotid endarterectomy samples (ten men/ten women) were obtained, and intraplaque biopsies from three distinct regions (internal control, fatty streak and plaque) were analysed by tandem-mass spectrometry. Multivariate statistical modelling, using orthogonal partial least square-discriminant analysis, was used to discriminate the proteomes between men and women.ResultsMultivariate discriminant modelling revealed proteins from 16 functional groups that displayed sex-specific associations. Additional statistics revealed ten proteins that display region-specific alterations when comparing sexes, including proteins related to inflammatory response, response to reactive oxygen species, complement activation, transport and blood coagulation. Transport protein afamin and blood coagulation proteins antithrombin-III and coagulation factor XII were significantly increased in plaque region from women. Inflammatory response proteins lysozyme C and phospholipase A2 membrane-associated were significantly increased in plaque region from men. Limitations with this study are the small sample size, limited patient information and lack of complementary histology to control for cell type differences between sexes.ConclusionsThis pilot study, for the first time, utilises a multivariate proteomic approach to investigate sexual dimorphism in human atherosclerotic tissue, and provides an essential proteomic platform for further investigations to help understand sexual dimorphism and plaque vulnerability in atherosclerosis.
Highlights
Atherosclerosis is a multifaceted chronic disease of the arterial wall that is the major cause of cardiovascular disease, the leading cause of mortality in many countries [1]
A full identification list has been presented as a supplement to our previous work by Liang and colleagues [13]; the current tandem-mass spectrometry results were used as validation of previous reported results where only 41 protein identities from the tandem-mass spectrometry were analysed [13]
Carotid atherosclerotic lesions were obtained from men and women, where comparative distinct regions of interest were sampled for proteomic analysis by tandem-mass spectrometry together with multivariate and univariate statistical analyses
Summary
Atherosclerosis is a multifaceted chronic disease of the arterial wall that is the major cause of cardiovascular disease, the leading cause of mortality in many countries [1] The epidemiology of this disease shows distinct differences between men and women, with women developing atherosclerosis later in life than men and rapidly developing post-menopause [2, 3]. Atherosclerotic lesions have a high degree of heterogeneity in relation to their morphology and composition; this heterogeneity can affect the progression of atherosclerosis and clinical outcomes [10]. One such morphological feature that can predict the outcome and severity of plaque rupture is the amount of intraplaque haemorrhage present. We aimed to investigate the differences in proteomic profiles between sexes, including distinct lesion regions, to identify altered proteins that contribute to these differences observed clinically
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