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Current Trends in Endocrinology   Volumes    Volume 9 
Endothelium-specific up-regulation of heme oxygenase-1 by lentiviral transduction promotes release of positive regulators of adipocyte function, including Angiopoietin-1
Lars Bellner, Luca Vanella, Nader G. Abraham
Pages: 31 - 43
Number of pages: 13
Current Trends in Endocrinology
Volume 9 

Copyright © 2017 Research Trends. All rights reserved

Crosstalk between perivascular adipose tissue and endothelial cells (EC) is thought to modulate vascular homeostasis, though the paracrine regulatory effects of dysfunctional endothelium on adipose tissue remain unclear. We explored the hypothesis that endothelial function affects adipocyte function. Our previous studies have shown that angiotensin II (AngII) causes endothelial dysfunction. Our preliminary results in mouse pre-adipocytes show that AngII increases lipogenesis. Consequently, human microvessel endothelial cells (HMEC-1, hereafter referred to as EC) were treated with AngII in the presence and absence of the heme oxygenase-1 (HO-1) inducer, Cobalt protoporphyrin (CoPP), with or without the HO activity inhibitor tin mesoporphyrin (SnMP). Ten percent conditioned media (CM) from EC was added to mesenchymal stem cell (MSC)-derived adipocytes. Adipocytes incubated with CM from AngII-treated EC showed a marked increase in adipogenesis, whereas adipocytes incubated with CM from AngII-treated EC concomitantly treated with CoPP attenuated adipogenesis. In contrast, CM from EC treated with AngII together with SnMP increased MSC-adipogenesis. We targeted vascular endothelial cells with a lentiviral (lenti) construct expressing human HO-1 under the control of an endothelium-specific promoter (VECAD-HO-1). MSCs exposed to CM from VECAD-HO-1-transduced EC exhibited a reduction in adipogenesis and lipid droplet size (10.2 ± 1 at 490 nm) as compared to MSCs exposed to CM from VECAD-GFP-treated EC (17.0 ± 2, p < 0.05). Furthermore, VECAD-HO-1-transduced EC expressed lower levels of soluble intercellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) when compared to control, suggesting that increased levels of EC HO-1 improved EC function. This effect was reversed by SnMP. Adipocytes treated with CM from VECAD-HO-1-transduced EC exposed to SnMP displayed increased adipogenesis and adipocyte hypertrophy (24.5 ± 1, p < 0.01). Finally, when CM from VECAD-HO-1-transduced cells was tested for paracrine growth factors, including vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Angpt1), the latter proved most effective in ameliorating adipocyte dysfunction. Thus, increased HO-1 expression in EC attenuated adipogenesis and prevented adipocyte dysfunction.
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