Dataset Information

Circulating Cells in Coronary Collateral Artery Growth

ABSTRACT: Background: Collateral artery growth, also termed arteriogenesis, occurs upon narrowing or occlusion of a major artery. To date, attempts to stimulate arteriogenesis in patients for therapeutic purposes have not been successful. Experimental models showed that circulating cells orchestrate arteriogenesis. In humans, a large heterogeneity exists in the arteriogenic response. We hypothesized that good arteriogenic responders (GARs) and bad arteriogenic responders (BARs) differ in gene expression profiles of circulating cells, thereby disclosing potential new therapeutic strategies for the stimulation of arteriogenesis. Methods: A total of 45 patients scheduled for percutaneous coronary intervention (PCI) for single-vessel coronary artery disease underwent intracoronary measurements of collateral flow index (CFI) to distinguish between GARs (CFI>0.21) and BARs (CFI≤0.21). Monocytes and CD34+ stem cells were collected from peripheral blood. A fraction of monocytes was further processed to obtain stimulated monocytes and macrophages. Whole genome transcriptome analysis was performed on all four cell types. Results: LPS-stimulated monocytes showed 244 genes differentially expressed (false discovery rate < 0.05) between GARs and BARs. Macrophage gene expression correlated with stimulated monocytes, while resting monocytes and stem cells revealed no differential gene expression. Stimulated monocytes from GARs showed a strongly attenuated response in several interferon- and apoptosis-related genes, which was corroborated at the protein level. Conclusions Circulating cells from GARs and BARs distinctively differ in their gene expression profiles upon stimulation. The reduced expression of interferon and apoptosis genes in GARs may lead to novel therapeutic approaches for the stimulation of collateral artery growth. Keywords: disease state analysis, stress response analysis, natural defense mechanism analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE7547 | GEO | 2008/04/17

SECONDARY ACCESSION(S): PRJNA99379

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:This study characterizes the response of primary human endothelial cells (human umbilical vein endothelial cells, HUVECs) to the relative shear stress changes that occur during the initiation of arteriogenesis at the entrance regions to a collateral artery network. HUVECs were preconditioned to a baseline level of unidirectional shear of 15 dynes/cm2 for 24 hours. After 24 hours preconditioning, HUVECs were subjected to an arteriogenic stimulus that mimics the shear stress changes observed in the opposing entrance regions into a collateral artery network. The arteriogenic stimulus consisted of a 100% step wise increase in shear stress magnitude to a unidirectional 30 dynes/cm2 in either the same or opposite direction of the preconditioned shear stress. This simulates either the feeding entrance to the collateral artery circuit or the region that drains into the vasculature downstream of an obstruction in a major artery, respectively. In vivo analysis of collateral growth in the mouse hindlimb showed enhanced outward remodeling in the re-entrant (direction reversing) region that reconnects to the downstream arterial tree, suggesting reversal of shear stress direction as a key enhancer of arteriogenesis. Transcriptional profiling using microarray techniques identified that the reversal of shear stress direction, but not an increase in shear stress alone, yielded a broad-based enhancement of the mechanotransduction pathways necessary for the induction of arteriogenesis. Human umbilical vein endothelial cells (HUVECs) were preconditioned to a unidirectional clockwise shear stress of 15 dynes/cm2 for 24 hours. An acute increase in shear stress magnitude to 30 dynes/cm2 in either a clockwise (non-reversed) or counter-clockwise (reversed) direction was applied for 6 hours. An additional preconditioned control culture was maintained under a unidirectional clockwise shear stress of 15 dynes/cm2 and harvested at the same time point, 6 hours post-conditioning. Each condition of reversed, non-reversed, and control was performed in tandem from the same starting cell culture as one replicate. The total experiment consisted of four replicates. Gene transcription was then assessed using microarray expression analysis.

Dataset Information

Circulating Cells in Coronary Collateral Artery Growth

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets