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Decreased autophagic flux as a mechanism of glucose‐ and fatty acid‐induced dysfunction in human aortic endothelial cells
Author(s) -
Weikel Karen Anne,
Ido Yasuo,
Ruderman Neil
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.565.6
Subject(s) - autophagy , ampk , chemistry , endothelial dysfunction , amp activated protein kinase , flux (metallurgy) , glycolysis , microbiology and biotechnology , medicine , endocrinology , protein kinase a , biochemistry , biology , metabolism , kinase , apoptosis , organic chemistry
The mechanisms by which cellular stress influences autophagic flux in cardiovascular disease vary between tissues and cellular contexts. The cellular response to glucose and fatty acids is regulated by adenosine monophosphate‐activated protein kinase (AMPK), but whether AMPK influences the effects of hyperglycemia and hyperlipidemia on autophagy in endothelial cells remains to be established. In human aortic endothelial cells (HAECs), we evaluated the effects of glucose and fatty acids on endothelial dysfunction by measuring transcription of endothelial nitric oxide synthase, adhesion of THP‐1 monocytes, and cellular ATP levels. Autophagic flux was assessed based upon expression levels of p62 and LC3‐II. Compared to HAECs in non‐stressed conditions, HAECs exposed to elevated concentrations of glucose and palmitate had a smaller ATP/ADP ratio and showed increased adhesion of monocytes. Under these hyperglycemic and hyperlipidemic conditions, autophagic flux was also decreased. Activation of AMPK attenuated glucose‐ and palmitate‐induced changes in these parameters, and chemical induction of autophagic flux diminished glucose‐ and palmitate‐induced changes in ATP/ADP and monocyte adhesion. Up‐regulation of autophagic flux may be one way in which AMPK can ameliorate glucose‐ and palmitate‐induced dysfunction in HAECs. Research support was provided by NIH/NHLBI HL068758