Spatial Gene Expression of Human Coronary Arteries Revealed the Molecular Features of Diffuse Intimal Thickening in Explanted Hearts
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ABSTRACT:
PROVIDER: PRJNA1192993 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31569555_1.fastq.gz | Fastqsanger.gz | |||
| SRR31569555_2.fastq.gz | Fastqsanger.gz | |||
| SRR31569556_1.fastq.gz | Fastqsanger.gz | |||
| SRR31569556_2.fastq.gz | Fastqsanger.gz | |||
| SRR31569557_1.fastq.gz | Fastqsanger.gz |
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Project description:Diffuse intimal thickening (DIT) is a pre-clinical stage of atherosclerosis characterized by thickened intima. The molecular basis of its susceptibility to atherogenesis is unknown, and mechanistic investigations cannot be performed in commonly used mouse models, in which DIT does not exist. Vascular smooth muscle cells (SMCs) are the predominant cell type that occupies the intima and media of DIT. The molecular differences between these two layers may reveal the earliest phenotypic changes in SMCs to promote atherosclerosis. We benchmarked the RNA quality of human coronary arteries from autopsies (n = 7) and explanted hearts (n = 7) and performed Visium spatial gene expression on tissue sections with DIT. Although autopsy samples met the RNA quality standard for Visium (DV200 ≥ 30%), only arteries from explanted hearts exhibited reliable sequencing performance. Genes enriched in TGF-β-mediated remodeling of the extracellular matrix were overrepresented in the intima. SMCs enriched in the intima are dedifferentiated, but unlike those in the atherosclerotic lesions, they are not pro-inflammatory. Our findings indicate that autopsy samples are not ideal to distinguish subtle differences among cell phenotypes. SMCs in thickened intima may lead to lipid retention but not necessarily the onset of atherosclerosis.
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Project description:Phenotypic heterogeneity among arterial ECs is particularly relevant to atherosclerosis since the disease occurs predominantly in major arteries, which vary in their atherosusceptibility. To explore EC heterogeneity, we used DNA microarrays to compare gene expression profiles of freshly harvested porcine coronary and iliac artery ECs. We demonstrate that in vivo the endothelial transcriptional profile of a coronary artery (the right coronary artery) is intrinsically different from that of a major conduit vessel (the external iliac artery), and that this difference is consistent with former vessel being more prone to atherosclerosis. Keywords: coronary atherosclerosis, endothelial heterogeneity, microarray, gene expression Endothelial cells were freshly harvest from right coronary, left and right iliac arteries from four pigs. RNA were isolated and expression profiles were obtained using olig microarrays.
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