Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jan;298(1):H163-70.
doi: 10.1152/ajpheart.00652.2009. Epub 2009 Nov 6.

Prelesional Arterial Endothelial Phenotypes in Hypercholesterolemia: Universal ABCA1 Upregulation Contrasts With Region-Specific Gene Expression in Vivo

Affiliations
Free PMC article

Prelesional Arterial Endothelial Phenotypes in Hypercholesterolemia: Universal ABCA1 Upregulation Contrasts With Region-Specific Gene Expression in Vivo

Mete Civelek et al. Am J Physiol Heart Circ Physiol. .
Free PMC article

Abstract

Atherosclerosis originates as focal arterial lesions having a predictable distribution to regions of bifurcations, branches, and inner curvatures where blood flow characteristics are complex. Distinct endothelial phenotypes correlate with regional hemodynamics. We propose that systemic risk factors modify regional endothelial phenotype to influence focal susceptibility to atherosclerosis. Transcript profiles of freshly isolated endothelial cells from three atherosusceptible and three atheroprotected arterial regions in adult swine were analyzed to determine the initial prelesional effects of hypercholesterolemia on endothelial phenotypes in vivo. Cholesterol efflux transporter ATP-binding cassette transporter A1 (ABCA1) was upregulated at all sites in response to short-term high-fat diet. Proinflammatory and antioxidative endothelial gene expression profiles were induced in atherosusceptible and atheroprotected regions, respectively. However, markers for endoplasmic reticulum stress, a signature of susceptible endothelial phenotype, were not further enhanced by brief hypercholesterolemia. Both region-specific and ubiquitous (ABCA1) phenotype changes were identified as early prelesional responses of the endothelium to hypercholesterolemia.

Figures

Fig. 1.
Fig. 1.
Oil Red O staining in multiple arterial regions of normal and hypercholesterolemic animals. Frozen sections from three atheroprotected (carotid, descending artery, and renal artery) and two atherosusceptible (aortic arch, abdominal aorta) samples were stained with Oil Red O, followed by hematoxylin, for the detection of lipid deposits and cell histology. Scale bar is 100 μm.
Fig. 2.
Fig. 2.
ATP-binding cassette transporter A1 (ABCA1) gene expression in normal and hypercholesterolemic animals. ABCA1 transcript expression was normalized to glyceraldehydes-3-phosphate dehydrogenase (GAPDH) in normal and hypercholesterolemic animals in six different regions. AA, aortic arch; AbA, abdominal aorta; RB, renal branch; C, common carotid artery; DT, descending thoracic aorta; RA, renal artery; NC, normocholesterolemia; HC, hypercholesterolemia. Data are presented as means ± SE. Significance was assessed by one-sided (for upregulation) t-test. *P < 0.05 and **P < 0.01.
Fig. 3.
Fig. 3.
ABCA1 protein expression in normal and hypercholesterolemic animals. Arteries were frozen in optimum-cutting temperature compound, sectioned, and stained with an antibody against ABCA1 antigen using standard immunohistochemistry techniques. Scale bar is 20 μm.
Fig. 4.
Fig. 4.
Endoplasmic reticulum stress and unfolded protein response pathway gene expression in normal and hypercholesterolemic animals. Transcript expression was normalized to GAPDH in normal and hypercholesterolemic animals in two different regions. HSP, heat shock protein; ATF6α, activating transcription factor 6α; XBP1, X-box binding protein 1. Data are presented as means ± SE. Significance was assessed by Student's t-test. No significance was found between NC and HC samples.

Similar articles

See all similar articles

Cited by 9 articles

See all "Cited by" articles

Publication types

MeSH terms

Substances

Feedback