ArticleProceedings of the National Academy of Sciences of the United States of America2004
Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03829046 (The Effects of Evolocumab on Endothelial and Inflammatory Biocellular Markers in Patients With Diabetes and Atherosclerotic Vascular Disease), which is not on this map. Cited by 273 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effects of Evolocumab on Endothelial and Inflammatory Biocellular Markers in Patients With Diabetes and Atherosclerotic Vascular Disease (METCHNIKOFF)
Open the trial in the graphWho cites it
273 citing papers in PubMed, 1 synthesis or guideline pooled it, 662 citations in OpenAlex.
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213 more citing papers are in PubMed but not listed here.
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9 authors at 3 institutions in 1 country.
Funding
Abstract
Atherosclerotic lesion localization to regions of disturbed flow within certain arterial geometries, in humans and experimental animals, suggests an important role for local hemodynamic forces in atherogenesis. To explore how endothelial cells (EC) acquire functional/dysfunctional phenotypes in response to vascular region-specific flow patterns, we have used an in vitro dynamic flow system to accurately reproduce arterial shear stress waveforms on cultured human EC and have examined the effects on EC gene expression by using a high-throughput transcriptional profiling approach. The flow patterns in the carotid artery bifurcations of several normal human subjects were characterized by using 3D flow analysis based on actual vascular geometries and blood flow profiles. Two prototypic arterial waveforms, "athero-prone" and "athero-protective," were defined as representative of the wall shear stresses in two distinct regions of the carotid artery (carotid sinus and distal internal carotid artery) that are typically "susceptible" or "resistant," respectively, to atherosclerotic lesion development. These two waveforms were applied to cultured EC, and cDNA microarrays were used to analyze the differential patterns of EC gene expression. In addition, the differential effects of athero-prone vs. athero-protective waveforms were further characterized on several parameters of EC structure and function, including actin cytoskeletal organization, expression and localization of junctional proteins, activation of the NF-kappaB transcriptional pathway, and expression of proinflammatory cytokines and adhesion molecules. These global gene expression patterns and functional data reveal a distinct phenotypic modulation in response to the wall shear stresses present in atherosclerosis-susceptible vs. atherosclerosis-resistant human arterial geometries.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.