Evious CMV infection may alter the function of vascular smooth muscle cells permanently. Relatively little is known about the cell tropism of CMV in vivo but the endothelium is certainly a reservoir for infection. Indeed, CMV-specific T cells demonstrate the characteristic feature of CX3CR1 expression that targets these cells to stressed endothelial cells through fractalkine binding [25]. Some studies [26,27], although not all [28,29], have also shown an association between CMV seropositivity and endothelial dysfunction. We did not include any measures of endothelial function in our study but this is certainly an area that warrants further investigation. Chronic inflammation has long been recognized as a cardiovascular risk factor and a clear association also exists between inflammation and arterial stiffness, as demonstrated by studies of conditions characterized by chronic systemic inflammation including CKD and in the general population [3]. More specifically, aortic inflammation, as assessed using positron emission tomography imaging, has recently been shown to influence aortic PWV [30]. Although only measured at a single time point, we found no differences in hsCRP or serum albumin concentrations between CMV seropositive and seronegative patients in our analyses. This does not support chronic inflammation as a possible explanation for our findings. Chronic kidney disease is associated with the relative accumulation of many serum proteins and it is possible that even mild states of CKD could be associated with increased rates of sub-clinical CMV reactivation, although this has not been investigated in this patient group [31]. A very close relationship exists between arterial stiffness and BP and this raises the possibility of whether or not CMV infection may also directly influence BP through secondary effects on arterial wall function. Interestingly, high CMV antibody titres have recently been shown to be independently associated with increased BP in healthy young Finnish men but not women [32]. Furthermore, CMV ribonucleic acid copy number was associated with hypertension in a Chinese cohort [33]. Nevertheless, our finding of an increase in arterial stiffness associated with CMV seropositivity was independent of BP, suggesting a direct effect on blood vessels themselves. Interestingly, a murine model of CMV infection is associated with increased blood pressure independent of a high cholesterol 18325633 diet and atheroma formation. In addition to stimulating expression of inflammatory cytokines, CMV infection also increased the synthesis of renin and angiotensin II [34]. The renin-angiotensin-aldosterone system is known to increase arterial stiffness and this is an area that warrants further investigation [3]. The visco-elastic properties of the aorta vary along its length, with a gradual decrease in both collagen and elastin content from proximal to distal [3]. Furthermore, it is becoming increasingly recognized that VSMC in different arteries, or SIS-3 site 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 BTZ043 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.Evious CMV infection may alter the function of vascular smooth muscle cells permanently. Relatively little is known about the cell tropism of CMV in vivo but the endothelium is certainly a reservoir for infection. Indeed, CMV-specific T cells demonstrate the characteristic feature of CX3CR1 expression that targets these cells to stressed endothelial cells through fractalkine binding [25]. Some studies [26,27], although not all [28,29], have also shown an association between CMV seropositivity and endothelial dysfunction. We did not include any measures of endothelial function in our study but this is certainly an area that warrants further investigation. Chronic inflammation has long been recognized as a cardiovascular risk factor and a clear association also exists between inflammation and arterial stiffness, as demonstrated by studies of conditions characterized by chronic systemic inflammation including CKD and in the general population [3]. More specifically, aortic inflammation, as assessed using positron emission tomography imaging, has recently been shown to influence aortic PWV [30]. Although only measured at a single time point, we found no differences in hsCRP or serum albumin concentrations between CMV seropositive and seronegative patients in our analyses. This does not support chronic inflammation as a possible explanation for our findings. Chronic kidney disease is associated with the relative accumulation of many serum proteins and it is possible that even mild states of CKD could be associated with increased rates of sub-clinical CMV reactivation, although this has not been investigated in this patient group [31]. A very close relationship exists between arterial stiffness and BP and this raises the possibility of whether or not CMV infection may also directly influence BP through secondary effects on arterial wall function. Interestingly, high CMV antibody titres have recently been shown to be independently associated with increased BP in healthy young Finnish men but not women [32]. Furthermore, CMV ribonucleic acid copy number was associated with hypertension in a Chinese cohort [33]. Nevertheless, our finding of an increase in arterial stiffness associated with CMV seropositivity was independent of BP, suggesting a direct effect on blood vessels themselves. Interestingly, a murine model of CMV infection is associated with increased blood pressure independent of a high cholesterol 18325633 diet and atheroma formation. In addition to stimulating expression of inflammatory cytokines, CMV infection also increased the synthesis of renin and angiotensin II [34]. The renin-angiotensin-aldosterone system is known to increase arterial stiffness and this is an area that warrants further investigation [3]. The visco-elastic properties of the aorta vary along its length, with a gradual decrease in both collagen and elastin content from proximal to distal [3]. Furthermore, it is becoming increasingly recognized that VSMC in different arteries, or 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.
