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Observational Study
. 2022 Mar 21;22(1):118.
doi: 10.1186/s12872-021-02421-8.

Clinical relevance of circulating angiogenic cells in patients with ischemic stroke

Affiliations
Observational Study

Clinical relevance of circulating angiogenic cells in patients with ischemic stroke

Francisco Rodríguez-Esparragón et al. BMC Cardiovasc Disord. .

Abstract

Background: Endothelial progenitor cells (EPCs) are circulating angiogenic cells with endothelial features associated with risk for stroke. We aimed to delve into their functional characteristics. EPCs were isolated and cultured from Ischemic Stroke (IS) patients and predictors of their variance evaluated.

Methods: This is a single-center observational study evaluating 187 consecutively hospitalized patients with IS. EPCs were isolated from blood samples. The number of circulating angiogenic cells (CACs), colony-forming units (CFU-ECs) and the emergence of late outgrowths endothelial cells (LOECs) were counted. We collected clinical variables and measured the stromal cell-derived factor 1 alpha (SDF1α) serum levels. We also examined the relative telomere length and the expression of osteogenic gene markers in CACs.

Results: CACs counts and CFU-ECs colony numbers were positively correlated (rho = 0.41, p < 0.001, n = 187). We found significant differences according to whether thrombolytic treatment was performed in the distribution of CFU-ECs (odds ratio (OR) = 2.5; 95% confidence interval (CI) 1.01-6.35; p = 0.042) and CACs (OR = 4.45; 95% IC 1.2-15.5; p = 0.012). The main determinants of CACs variation were the number of risks factors, thrombolysis treatment, arterial hypertension, LOECs occurrence, and the vascular endothelial growth factor expression, whereas CFU-ECs variations depended on hemoglobin content and the relative reduction in the National Institutes of Health Stroke Scale (NIHSS) criteria. The main predictors of LOECs appearance were thrombolysis and length of hospital stay.

Conclusions: Our study supports the relevance of patient risk factors and treatments in the analysis of the functional properties of EPCs.

Keywords: Biomarkers; Circulating angiogenic cells; Colony forming cells; Endothelial progenitor cells; Functionality; Gene; Ischemic stroke; Late outgrowth endothelial cells.

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Conflict of interest statement

Authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Endothelial progenitor cells (EPCs). a Circulating angiogenic cells (CACs) constitute a cell population enriched in monocytes that exert their angiogenic effects via paracrine. b Colony-forming units (CFU-ECs) are EPCs that can be obtained under certain culture conditions formed by a combination of monocytes and T cells. CFU-ECs express endothelial markers but also myeloid and hematopoietic markers. c CACs cultured from patients were positive for Dil-Ac-LDL uptake (red areas) and FITC-UEA-I binding (green areas). d Box plot displaying the distribution if the CACs analyzed marker genes. e Agarose gel conformation of PCR amplicons sixes: (1) VEGF, (2) KDR, (3) CD31, (4) CD45 and CD133
Fig. 2
Fig. 2
Endothelial progenitor cells (EPCs). a Late outgrowth EPCs also referred to as late EPCs, blood outgrowth endothelial cells, and endothelial outgrowth cells, are the only EPC subset faithfully belonging to the endothelial lineage. b Linear plot displaying the distribution of analyzed marker genes according cell passages
Fig. 3
Fig. 3
a Box plot showing the mean analyzed osteogenic and CXCL12/CXCR4/CXCR7 chemokine axis gene markers expression in CACs. Whiskers and box bands denote quartiles. b Box plot showing gene expression between male and female. Comparison using Mann–Whitney U-test for independent samples showed significant differences (*p = 0.03, **p = 0.006, ***p = 0.009)

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