Dataset Information

Low Coronary Wall Shear Stress Is Associated With Severe Endothelial Dysfunction in Patients With Nonobstructive Coronary Artery Disease.

ABSTRACT: OBJECTIVES:This study investigated the relationship between low wall shear stress (WSS) and severe endothelial dysfunction (EDFx). BACKGROUND:Local hemodynamic forces such as WSS play an important role in atherogenesis through their effect on endothelial cells. The study hypothesized that low WSS independently predicts severe EDFx in patients with coronary artery disease (CAD). METHODS:Forty-four patients with CAD underwent coronary angiography, fractional flow reserve, and endothelial function testing. Segments with >10% vasoconstriction after acetylcholine (Ach) infusion were defined as having severe EDFx. WSS, calculated using 3-dimensional angiography, velocity measurements, and computational fluid dynamics, was defined as low (<1 Pa), intermediate (1 to 2.5 Pa), or high (>2.5 Pa). RESULTS:Median age was 52 years, 73% were women. Mean fractional flow reserve was 0.94 ± 0.06. In 4,510 coronary segments, median WSS was 3.67 Pa. A total of 24% had severe EDFx. A higher proportion of segments with low WSS had severe EDFx (71%) compared with intermediate WSS (22%) or high WSS (23%) (p < 0.001). Segments with low WSS demonstrated greater vasoconstriction in response to Ach than did intermediate or high WSS segments (-10.7% vs. -2.5% vs. +1.3%, respectively; p < 0.001). In a multivariable logistic regression analysis, female sex (odds ratio [OR]: 2.44; p = 0.04), diabetes (OR: 5.01; p = 0.007), and low WSS (OR: 9.14; p < 0.001) were independent predictors of severe EDFx. CONCLUSIONS:In patients with nonobstructive CAD, segments with low WSS demonstrated more vasoconstriction in response to Ach than did intermediate or high WSS segments. Low WSS was independently associated with severe EDFx.

SUBMITTER: Kumar A

PROVIDER: S-EPMC6217963 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Low Coronary Wall Shear Stress Is Associated With Severe Endothelial Dysfunction in Patients With Nonobstructive Coronary Artery Disease.

Kumar Arnav A Hung Olivia Y OY Piccinelli Marina M Eshtehardi Parham P Corban Michel T MT Sternheim David D Yang Boyi B Lefieux Adrien A Molony David S DS Thompson Elizabeth W EW Zeng Wenjie W Bouchi Yasir Y Gupta Sonu S Hosseini Hossein H Raad Mohamad M Ko Yi-An YA Liu Chang C McDaniel Michael C MC Gogas Bill D BD Douglas John S JS Quyyumi Arshed A AA Giddens Don P DP Veneziani Alessandro A Samady Habib H

JACC. Cardiovascular interventions 20180926 20

<h4>Objectives</h4>This study investigated the relationship between low wall shear stress (WSS) and severe endothelial dysfunction (EDFx).<h4>Background</h4>Local hemodynamic forces such as WSS play an important role in atherogenesis through their effect on endothelial cells. The study hypothesized that low WSS independently predicts severe EDFx in patients with coronary artery disease (CAD).<h4>Methods</h4>Forty-four patients with CAD underwent coronary angiography, fractional flow reserve, and ...[more]

PMID: 30268874

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Project description:Aim: To survey the alteration of endothelial transcriptome under different types of shear stress and find novel shear stress-sensitive protein-coding genes as well as non-coding RNAs as potential therapeutic targets for the treatment of atherosclerosis Method: After exposed to LS, OS and ST for 24 hours (n=4, respectively), ECs were harvested by scraping, and RNA was isolated and purified. Double-stranded cDNA was generated from 100 to 150 ng of total qualified RNA using selective priming and prepared for the final library. Quantitative PCR (qPCR) was performed to quantify the library using a KAPA kit for Illumina sequencing platforms. Twelve samples were then clustered on the cBot and sequenced on a 50-cycle single end on a HiSeq 2000 to generate 50 bp paired-end reads, using TruSeq SBS v3 reagents according to manufacturer’s protocols. RNA-seq fastq files were aligned to the human genome primary assembly (GRCh38) using the Subread package. Read counts on each gene were determined by featureCounts function in the Subread package using GeneCode human GTF file version 23 (http://www.gencodegenes.org/). Differential expression analysis between endothelial cells under different types of shear stress were performed using the limma package with the voom transformation. P values were adjusted by default Benjamini-Hochberg procedure. Results: RNA-seq data provided a broad view of endothelial transcriptome under shear stress. We mapped about 70 million reads and discovered over 16,000 genes that are well-expressed in human coronary artery endothelial cells. RNA-seq results were consistent with previously reported DNA microarray data and we also confirmed the expression of genes that are previously reported and novel genes with qRT–PCR results. Comparing the endothelial transcriptomes under different types of shear stress, we found that there are approximately 50% genes that are differentially expressed in ECs under ST vs. LS and OS vs. LS while 10% under ST vs. OS. Conclusion: RNA-seq data provide a framework for investigating endothelial transcriptome under shear stress. We found that endothelial cells under LS condition profoundly differs from those under either ST or OS conditions. The profiling also reveals a large amount of novel shear sensitive genes and lncRNAs that are not reported before. It provides the community with potential targets for anti-atherosclerosis drug development considering the determinant role of shear stress in the distribution of atherosclerotic lesions in the arterial tree.

Dataset Information

Low Coronary Wall Shear Stress Is Associated With Severe Endothelial Dysfunction in Patients With Nonobstructive Coronary Artery Disease.

Publications

Low Coronary Wall Shear Stress Is Associated With Severe Endothelial Dysfunction in Patients With Nonobstructive Coronary Artery Disease.

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