<p><b>A</b>. Correlations between several cardiovascular-specific genes. <b&... more <p><b>A</b>. Correlations between several cardiovascular-specific genes. <b>B</b>. Correlations between selected vascular and primitive genes in the same population. <b>C</b>. Correlations between other tissue-specific and primitive genes. <b>D</b>. Inverse correlation between the expression of vascular genes and a leukocyte gene (PTPRC/CD45). In all the graphs, the number of subjects is n = 26, R<sup>2</sup> is the linear regression coefficient, and p indicates significance; these coefficients were placed in mirror positions across the diagonal with their corresponding graphs. The data represent RCNs.</p
Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells ... more Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their coexpressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p,0.03) with age (R 2 = 20.23), vascular stiffness (R 2 = 20.24), and central aortic pressure (R 2 = 20.19) and positively correlated with body mass index (R 2 = 0.72, in women). The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72622% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional network. Furthermore, the coordinated gene expression in these modules can be linked to cardiovascular risk factors and subclinical cardiovascular disease; thus, this measure may be useful for their diagnosis and prognosis.
<p><b>A</b>. Correlations between several cardiovascular-specific genes. <b&... more <p><b>A</b>. Correlations between several cardiovascular-specific genes. <b>B</b>. Correlations between selected vascular and primitive genes in the same population. <b>C</b>. Correlations between other tissue-specific and primitive genes. <b>D</b>. Inverse correlation between the expression of vascular genes and a leukocyte gene (PTPRC/CD45). In all the graphs, the number of subjects is n = 26, R<sup>2</sup> is the linear regression coefficient, and p indicates significance; these coefficients were placed in mirror positions across the diagonal with their corresponding graphs. The data represent RCNs.</p
Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells ... more Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their coexpressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p,0.03) with age (R 2 = 20.23), vascular stiffness (R 2 = 20.24), and central aortic pressure (R 2 = 20.19) and positively correlated with body mass index (R 2 = 0.72, in women). The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72622% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional network. Furthermore, the coordinated gene expression in these modules can be linked to cardiovascular risk factors and subclinical cardiovascular disease; thus, this measure may be useful for their diagnosis and prognosis.
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