Abnormal Endothelial Gene Expression Associated With Early Coronary Atherosclerosis.

Journal of the American Heart Association
Robert P HebbelAmir Lerman

Abstract

Background We examined feasibility of a unique approach towards gaining insight into heritable risk for early atherosclerosis: surveying gene expression by endothelial cells from living subjects. Methods and Results Subjects aged <50 years (mean age, 37; range, 22-49) without obstructive coronary artery disease underwent coronary reactivity testing that identified them as having normal or abnormal coronary endothelial function. Cultures of Blood Outgrowth Endothelial Cells (BOEC) from 6 normal and 13 abnormal subjects passed rigorous quality control and were used for microarray assessment of gene expression. Of 9 genes differentially expressed at false discovery rate <0.1%, we here focus upon abnormal subjects having elevated expression of HMGB1 (high mobility group box 1) which we unexpectedly found to be linked to low LAMC1 (laminin gamma 1) expression. This linkage was corroborated by 3 of our past studies and confirmed bio-functionally. Compared with normal BOEC, abnormal BOEC released 13±3-fold more HMGB1 in response to lipopolysaccharide; and they deposited one tenth as much LAMC1 into collagen subendothelial matrix during culture. Clinical follow-up data are provided for 4 normal subjects (followed 13.4±0.1 year) and for...Continue Reading

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Citations

Aug 1, 2021·American Journal of Hematology·Robert P Hebbel, Gregory M Vercellotti

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Datasets Mentioned

BETA
GSE132651
GSE22688
GSE9877

Methods Mentioned

BETA
light microscopy
FACS
ELISA

Software Mentioned

R
R package “ samr ” for Significance Analysis of Microarrays
genomatix
R package “ randomForest
Ensembl
Ingenuity Pathway Analysis
PathwayCommons
BOEC
Enrichr
miRbase

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