Endocrine Abstracts

Endothelial cells (ECs) have major role in post-ischemic angiogenesis. Trimethylation of lysine 27 of histone3 (H3K27me3) is a repressive epigenetic mark carried by EZH2 enzyme, the catalytic part of Polycomb complex2 (PRC2, also comprising the suppressor of zeste 12 homolog (Suz12)). We investigated if in vitro hypoxia and in vivo limb ischemia affect the expression of PRC2 in ECs and mouse limb muscles, respectively. Then, modulation of angiogenic genes by ...

Objectives: Endothelial cells (ECs) have major role in post-ischemic angiogenesis. EZH2 (enhancer of zest homology) carries out trimethylation of lysine 27 on histone3 (H3K27me3) – repressive mark, thus modulating gene expression. We tested if the EZH2 inhibitor 3-deazaneplanocin (DZNep) regulates angiogenesis under hypoxia and limb ischemia (LI) in vivo in ECs and mouse limb muscles respectively.Methods: Human umbilical vein ECs...

Endothelial cells (ECs) may display distorted epigenetic features in diabetes mellitus (DM) but this has not been investigated under combined conditions of diabetes and limb ischemia. Initial screening for histone H3 and H4 trimethylation (me3) and panacetylation of lysine residues (causing transcriptional repression and activation) were conducted using two models of hyperglycemia and ischemia. Human umbilical vein ECs (HUVECs) were cultured in EGM2 or EBM2 media (low growth f...

Blood vessels supply nutrients, oxygen and other key molecules necessary for the function of all organs in the body. The endothelial cell (EC) repair and response to injury or hypoxia is also regulated by the interplay of chromatin-modifying enzymes. Likewise, dysregulation of the lymphatic system underlies the development of the metabolic syndrome. New technologies using omics approaches have now allowed the detection of chromatin and RNA molecules that directly interact in n...

7-Oxysterols modulate lipid transport and promote oxidative stress and apoptosis in the vascular wall. 7-Ketocholesterol (7KC) and 7β-hydroxycholesterol (7βOHC) are inter-converted by 11β-hydroxysteroid dehydrogenase-1 (11βHSD1), better known for metabolising glucocorticoids. Pharmacological inhibition of 11βHSD1 protects against atherosclerosis and these beneficial effects may be mediated through changes in glucocorticoids or oxysterols. To establish ...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids thus amplifying their intracellular actions. 11β-HSD1 deficiency or inhibition, which improve metabolic syndrome and attenuate atherosclerosis in vulnerable rodent strains, is a target for drug development. However, 11β-HSD1 also converts 7-ketocholesterol (7KC) (which accumulates in fatty tissues), to the potentially more atherogenic, 7β-hydroxycholesterol. Whether a...