11β-hydroxysteroid dehydrogenase type 1 gene expression is increased in ascending aorta tissue of metabolic syndrome patients with coronary artery disease

Abstract

ABSTRACT. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) 3123©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 3122-3132 (2012) 11β-HSD-1 expressed in ascending aorta of MS patient with CAD activity and mRNA levels are increased in visceral and subcutaneous adipose tissues of metabolic syndrome subjects. We analyzed 11β-HSD-1 expression in human epicardial adipose (EA) and ascending aorta (AA) tissues of metabolic syndrome patients and examined their contribution to the development of coronary atherosclerosis. The 11β-HSD-1 expression was evaluated by qRT-PCR in EA and AA tissues of 20 metabolic syndrome patients with coronary artery disease (metabolic syndrome group) and 10 non-metabolic syndrome patients without coronary artery disease (controls). 11β-HSD-1 expression was increased in EA and AA tissues of the metabolic syndrome group (4.1-and 5.5-fold, respectively). A significant positive correlation was found between 11β-HSD-1 expression in EA tissue and waist hip ratio and 11β-HSD-1 expression in AA tissue and body mass index, while a negative correlation was found between 11β-HSD-1 expression in EA tissue and HDL. Expression of CD68, a macrophage marker, was significantly increased in both tissues of the metabolic syndrome group; it was 2-fold higher in AA tissue compared to EA tissue in the metabolic syndrome group. Our findings of increased expression of 11β-HSD-1 and CD68 in AA tissue of the metabolic syndrome group lead us to suggest that they contribute to coronary atherosclerosis in metabolic syndrome. This positive correlation between obesity markers and 11β-HSD-1 in AA and EA tissues strengthens the evidence that 11β-HSD-1 has a role in metabolic syndrome. To the best of our knowledge, this is the first report showing 11β-HSD-1 and CD68 expression in AA tissue of metabolic syndrome patients. We suggest that there is tissue-specific expression of 11β-HSD-1 in metabolic syndrome and associated cardiovascular disorders.

11β-Hydroxysteroid Dehydrogenase 1: Translational and Therapeutic Aspects

“…In addition to the vasculature, 11␤-HSD1 is also expressed in macrophages (see Section X.B.). Little is known about the role of 11␤-HSD1 in atherosclerosis; however, a recent study demonstrated increased expression in the ascending aorta of patients with metabolic syndrome-associated coronary artery disease (178).…”

Pro-Inflammatory Cytokine Induction of 11β-hydroxysteroid Dehydrogenase Type 1 in A549 Cells Requires Phosphorylation of C/EBPβ at Thr235

“…Deficiency in, or inhibition of, 11β-HSD1 exacerbates acute inflammation although it is protective against the low-grade chronic inflammation associated with metabolic and cardiovascular disease [2,3]. 11β-HSD1 expression is increased at sites of inflammation, including in arthritis [4,5], obesity [6,7] and atherosclerosis [8], possibly mediated by the pro-inflammatory cytokines, IL-1α/β and TNFα, which increase levels of mRNA encoding 11β-HSD1 in a variety of cells [2]. The HSD11B1 gene encoding 11β-HSD1 is transcribed from two different promoters, P1 and P2, which by RNA splicing produce the same protein [9].…”

The Dehydrogenase Hypothesis

“…Mediastinal adipose tissue 11β (Beta)-HSD1 has been linked with coronary atherosclerosis [ 92 ]. The same authors demonstrated increased 11β (Beta)-HSD1 expression in aortas of obese patients with the metabolic syndrome [ 93 ]. 11β (Beta)-HSD1 inhibition in apoE knockout mice achieved signifi cant reduction atherosclerotic load suggesting a role in plaque formation [ 94 ].…”