Abstract 526: The Influence of Endothelium on Smooth Muscle-Derived α1-Integrin, ROS and Collagen IV Expression: Effects of High Glucose and Diabetes
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Abstract
The abnormal metabolism in diabetes facilitates the development of atherosclerotic cardiovascular disease. Consequently, can HUVECs (human-umbilical-vascular-endothelial-cells) transiently primed by high glucose (HG) or diabetic serum (DM) change HuVSMCs (Human-Vascular-Smooth- Muscle-Cells)-derived α1-integrin, ROS (Reactive Oxygen Species) and collagen IV expression? Is there a relationship between HuVSMCs-created α1-integrin expression, ROS production and collagen IV accumulation?
Conditioned medium (CM) from HUVECs, transiently primed by HG (CMHG) or DM (CMDM), was added to HuVSMCs. The expression of HuVSMCs-derived α1-integrin was measured with an in situ ELISA and the quantity of HuVSMCs-produced ROS was evaluated applying dihydro-rhodamine. The accumulation of HuVSMCs-secreted collagen IV was estimated in the medium by an ELISA. The isolated effect of reduced HuVSMCs-derived α1-integrin expression was elucidated by knock-down using siRNA whereas the impact of NADPH oxidase on HuVSMCs-derived ROS production was estimated using NADPH inhibition (Diphenyleneiodonium(DPI)).
CMHG and CMDM reduced HuVSMCs-derived α1-intergin expression while collagen IV and ROS production was increased. Immunopurified HSP90α from CMHG gave similar results whereas treatment with recombinant HSP90α has no impact. However, knock-down of α1-intergin increased HuVSMCs-derived collagen IV and ROS accumulation whereas reduced NADPH oxidase activity decreased ROS and collagen IV production but increased α1-intergin expression.
Previously, we showed that CMHG has increased pHSP90α (phosphorylated HSP90α) and now our observations suggest that HUVECs-derived pHSP90α down-regulate the expression of HuVSMCs-derived α1-integrin. The reduced presences of α1-integrin increased ROS and collagen IV expression from HuVSMCs. Consequently, HG and DM might via HUVECs-secreted pHSP90α act as potent modifiers of injury-induced changes within the arterial wall in diabetes.
Author Disclosures: T. Ledet: None. K. Smidt: None. B. Mumm: None.
- © 2014 by American Heart Association, Inc.
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- Abstract 526: The Influence of Endothelium on Smooth Muscle-Derived α1-Integrin, ROS and Collagen IV Expression: Effects of High Glucose and DiabetesThomas Ledet, Kamile Smidt and Birgitte MummArteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:A526, originally published September 3, 2014
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