15-LOX metabolites and angiogenesis: angiostatic effect of 15(S)-HPETE involves induction of apoptosis in adipose endothelial cells.

Sasikumar J Soumya,Pallu Reddanna,Perumana R Sudhakaran,Antony Helen,Sheela Binu

doi:10.7717/peerj.635

Sasikumar J Soumya, Pallu Reddanna + Show 3 more

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https://doi.org/10.7717/peerj.635

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Journal: PeerJ	Publication Date: Oct 21, 2014
Citations: 27	License type: cc-by

Affiliation: University of Hyderabad, University of Kerala

Abstract

Inflammation is critical in the dysregulated growth of adipose tissue and associated vascular dysfunctions. 15-Lipoxygenase metabolites, important mediators of inflammation in adipose tissue during obese conditions, may contribute to codependence of inflammation and angiogenesis in adipose tissue. We have already reported the pro-angiogenic effect of 15(S)-HETE in adipose tissue. The present study was designed to understand the effect of 15(S)-HPETE, precursor of 15(S)-HETE, on angiogenesis in adipose tissue. Results showed that 15(S)-HPETE exerts an anti-angiogenic effect in adipose tissue. This was evidenced from decreased endothelial sprouting in adipose tissue explants, inhibition of angiogenic phenotype in adipose endothelial cells, decreased production of CD31 and VEGF in endothelial cells treated with 15(S)-HPETE. Further studies to examine the molecular mechanism of anti-angiogenic effect of 15(S)-HPETE showed that it inhibited cell survival signaling molecule Akt and anti-apoptotic Bcl-2 and also activated caspase-3 in adipose endothelial cells. These observations indicate that 15(S)-HPETE exerts its angiostatic effect in adipose tissue by inducing apoptosis of endothelial cells.

Highlights

15-Lipoxygenase (15-LOX) and its metabolites seem to exhibit both pro-inflammatory and anti-inflammatory activities
Adipose tissue explants were maintained in culture in MCDB 131 medium in presence and absence of 15(S)-hydroperoxyeicosatetraenoic acids (HPETEs)
In control explants, sprouting started to appear on the third day of culture, whereas no significant sprouting was seen in adipose tissue explants treated with 15(S)-HPETE during this period suggesting the inhibitory effect of 15(S)-HPETE on adipose tissue-angiogenesis

Summary

Introduction

15-Lipoxygenase (15-LOX) and its metabolites seem to exhibit both pro-inflammatory and anti-inflammatory activities. Lipid mediators including Cyclooxygenase (COX) and Lipoxygenase (LOX) metabolites [prostaglandins, thromboxane, leukotrienes, lipoxins, epoxyeicosatrienoic acids, other fatty acid epoxides, hydroxyeicosatetraenoic acids], platelet-activating factor, lysophosphatidic acid, sphingosine-1-phosphate, 2-arachidonoyl glycerol and other lipid amides modulate low grade inflammation in adipose tissue (Iyer et al, 2010). We observed that 15(S)-HETE induced angiogenesis in stromovascular fractions of adipose tissue (Soumya et al, 2013). The effect of 15(S)-HPETE, precursor of 15(S)-HETE, on angiogenesis in adipose tissue is not clear. The objective of the present study was to examine whether 15(S)-HPETE affects angiogenesis in adipose tissue. The results presented here indicate that 15(S)-HPETE causes anti-angiogenic effect in stromovascular fractions of adipose tissue by induction of apoptosis in endothelial cells. Cell culture plastic wares and ELISA plates were purchased from NUNC, Denmark. 15(S)-HPETE was prepared by incubating arachidonic acid with 15-LOX, as described earlier (Mahipal et al, 2007)

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