R indeed portions of the same artery, have different phenotypic properties and embryonic origins. Vascular smooth muscle cells in the ascending aorta and arch derive from neural crest, whereas those in the descending aorta have a somitic origin [35]. In addition, VSMC from different embryonic origins respond in lineage-specific ways to common stimuli [35] and may well vary in both their relativetropism for, and metabolic response to, CMV infection. Importantly, VSMC phenotype has already been shown to directly determine susceptibility to CMV infection [36]. Our finding of an apparent different association between CMV seropositivity and distensibility at different aortic levels warrants confirmation in larger studies. Our study has a number of limitations. Most subjects were taking antihypertensive medication, as would be expected, and this could potentially affect the biophysical properties of the aorta. Despite this, however, we 
were still able to detect significant differences in PWV and aortic distensibility between CMV seropositive and seronegative patients. Our study was not powered to examine the influence of individual antihypertensive agents on arterial stiffness. We used peripheral brachial pulse pressures in the calculations of aortic distensibility as it was not technically possible to obtain central aortic pressures during image acquisition. Aortic distensibility values are slightly lower when brachial pulse pressures are used [37] although we do not believe 25837696 this would have appreciably affected the overall significance of our results. Given the strong relationship with socio-economic status 1317923 and CMV exposure, consideration of socio-economic status in relation to vascular function would have been a valuable measurement [6]. It is possible that measuring CMV DNA might have given some more information on Clavulanic acid potassium salt chemical information active CMV infection/reactivation. However, examining the potential effects of viral load would require a much larger study. Similarly, the CMV assay we used does not quantify CMV antibody titres which could also have yielded potentially interesting information. Our study was performed in patients with CKD who are known to have increased arterial stiffness. Our results therefore also need validating in other populations. Finally, our study is cross-sectional in design and therefore only significant associations and not causality can be determined. In summary, we have shown that CMV seropositivity is associated with increased arterial stiffness in a cohort of patients with early stage CKD, independent of age and blood pressure. Using a complementary imaging modality, we also observed a reduction in distensibility of the proximal and distal descending aorta. These findings have significant potential implications for the mechanism by which CMV infection might influence cardiovascular disease. Although confirmation in larger cohorts is required, our results highlight the fact that CMV seropositivity may not be as trivial as is KDM5A-IN-1 custom synthesis currently considered in non-heavily immunosuppressed individuals. Ultimately, reducing the prevalence of CMV seropositivity might be a potential way of reducing the burden of cardiovascular disease in the general population.Author ContributionsCritically revised and approved the final manuscript: NAW CDC NCE TP LH RPS SL JNT PM CJF. Conceived and designed the experiments: CJF JNT RPS PM. Performed the experiments: NAW CDC NCE TP LH SL. Analyzed the data: NAW CDC CJF. Contributed reagents/materials/ analysis to.R indeed portions of the same artery, have different phenotypic properties and embryonic origins. Vascular smooth muscle cells in the ascending aorta and arch derive from neural crest, whereas those in the descending aorta have a somitic origin [35]. In addition, VSMC from different embryonic origins respond in lineage-specific ways to common stimuli [35] and may well vary in both their relativetropism for, and metabolic response to, CMV infection. Importantly, VSMC phenotype has already been shown to directly determine susceptibility to CMV infection [36]. Our finding of an apparent different association between CMV seropositivity and distensibility at different aortic levels warrants confirmation in larger studies. Our study has a number of limitations. Most subjects were taking antihypertensive medication, as would be expected, and this could potentially affect the biophysical properties of the aorta. Despite this, however, we were still able to detect significant differences in PWV and aortic distensibility between CMV seropositive and seronegative patients. Our study was not powered to examine the influence of individual antihypertensive agents on arterial stiffness. We used peripheral brachial pulse pressures in the calculations of aortic distensibility as it was not technically possible to obtain central aortic pressures during image acquisition. Aortic distensibility values are slightly lower when brachial pulse pressures are used [37] although we do not believe 25837696 this would have appreciably affected the overall significance of our results. Given the strong relationship with socio-economic status 1317923 and CMV exposure, consideration of socio-economic status in relation to vascular function would have been a valuable measurement [6]. It is possible that measuring CMV DNA might have given some more information on active CMV infection/reactivation. However, examining the potential effects of viral load would require a much larger study. Similarly, the CMV assay we used does not quantify CMV antibody titres which could also have yielded potentially interesting information. Our study was performed in patients with CKD who are known to have increased arterial stiffness. Our results therefore also need validating in other populations. Finally, our study is 
cross-sectional in design and therefore only significant associations and not causality can be determined. In summary, we have shown that CMV seropositivity is associated with increased arterial stiffness in a cohort of patients with early stage CKD, independent of age and blood pressure. Using a complementary imaging modality, we also observed a reduction in distensibility of the proximal and distal descending aorta. These findings have significant potential implications for the mechanism by which CMV infection might influence cardiovascular disease. Although confirmation in larger cohorts is required, our results highlight the fact that CMV seropositivity may not be as trivial as is currently considered in non-heavily immunosuppressed individuals. Ultimately, reducing the prevalence of CMV seropositivity might be a potential way of reducing the burden of cardiovascular disease in the general population.Author ContributionsCritically revised and approved the final manuscript: NAW CDC NCE TP LH RPS SL JNT PM CJF. Conceived and designed the experiments: CJF JNT RPS PM. Performed the experiments: NAW CDC NCE TP LH SL. Analyzed the data: NAW CDC CJF. Contributed reagents/materials/ analysis to.
