Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3

Abstract

Darrow AL, Shohet RV, Maresh JG. Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3. Physiol Genomics 43: 1144 -1152, 2011. First published July 26, 2011 doi:10.1152/physiolgenomics.00035.2011.-To characterize the endothelial dysfunction associated with Type II diabetes, we surveyed transcriptional responses in the vascular endothelia of mice receiving a diabetogenic, high-fat diet. Tie2-GFP mice were fed a diet containing 60% fat calories (HFD); controls were littermates fed normal chow. Following 4, 6, and 8 wk, aortic and leg muscle tissues were enzymatically dispersed, and endothelial cells were obtained by fluorescence-activated cell sorting. Relative mRNA abundance in HFD vs. control endothelia was measured with long-oligo microarrays; highly dysregulated genes were confirmed by real-time PCR and protein quantification. HFD mice were hyperglycemic by 2 wk and displayed vascular insulin resistance and decreased glucose tolerance by 5 and 6 wk, respectively. Endothelial transcripts upregulated by HFD included galectin-3 (Lgals3), 5-lipoxygenase-activating protein, and chemokine ligands 8 and 9. Increased LGALS3 protein was detected in muscle endothelium by immunohistology accompanied by elevated LGALS3 in the serum of HFD mice. Our comprehensive analysis of the endothelial transcriptional response in a model of Type II diabetes reveals novel regulation of transcripts with roles in inflammation, insulin sensitivity, oxidative stress, and atherosclerosis. Increased endothelial expression and elevated humoral levels of LGALS3 supports a role for this molecule in the vascular response to diabetes, and its potential as a direct biomarker for the inflammatory state in diabetes. gene expression; microarray; vascular biology; endothelial dysfunction; metabolic syndrome TYPE II DIABETES IS ASSOCIATED with increased atherosclerosis, retinopathy, skin ulceration, and other vascular-related diseases, all of which may involve damaged or dysfunctional endothelium. A major consequence of diabetes is endothelial exposure to elevated glucose and fatty acids, leading to endothelial nitric oxide synthase uncoupling and subsequent generation of reactive oxygen and nitrogen species (46) as well as the formation of advanced glycation end-products (AGEs) (45). Furthermore, hyperinsulinemia and other hormonal changes can alter endothelial signaling pathways (34). These changes may promote inflammation, impair vasoregulation, disrupt hemostasis, and inhibit reverse cholesterol transport (2, 32). By examining the transcriptional changes that occur in both the micro-and macrovascular endothelium of mice exposed to a dietary model of Type II diabetes, we expect to gain further insight into the underlying mechanisms of the endothelial dysfunction characteristic of diabetes and the metabolic syndrome.Transcriptional analysis has been used to examine the responses of cultured endothelium exposed to high glucose and insulin (9, 44). However, an in vitro analysis may only partially reflect the co...

Vascular transcriptional alterations produced by juvenile obesity in Ossabaw swine

“…Current research indicates that LGALS3 is upregulated at the mRNA and protein level in unstable plaque regions of carotid endarterectomy specimens, compared with stable regions from the same patients (64). Furthermore, in a recent microarray study, the LGALS3 transcript was found to be upregulated in endothelial cells isolated from obese mice fed a high-fat diet (22). Similarly, LGALS3 is highly expressed in aortic samples from ApoEϪ/Ϫ mice on a high-fat diet and .…”

Czy galektyna-3 ma związek z nerkowym wydalaniem albumin w cukrzycy typu 2?

“…A study in mice with high-fat diet induced diabetes, it was shown a transcriptional upregulation of galectin-3/AGE-Receptör3 in the endothelial cells [14]. Since galectin-3 is a component of AGE-receptor complex expressed on the surface of renal cells including endothelial cells, galectin-3 upregulation could be involved in diabetic nephropathy development.…”

Timing of Galectin-1 Exposure Differentially Modulates Nipah Virus Entry and Syncytium Formation in Endothelial Cells

“…Moreover, since secreted galectins bind back to glycoproteins on the plasma membrane, as well as to glycans on extracellular matrix glycoproteins, galectins can be highly concentrated at the cell surface. Thus, the galectin-1 concentration used in these studies may reflect the physiologic concentration of galectin-1 encountered by a virus at the endothelial cell membrane (48)(49)(50)(51).…”