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Title: Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

Abstract

Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. --more » Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.« less

Authors:
 [1];  [2];  [1];  [3]; ;  [1]; ; ;  [4];  [5];  [6];  [1]
  1. Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)
  2. (China)
  3. Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan)
  4. Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan)
  5. Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China)
  6. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States)
Publication Date:
OSTI Identifier:
22212177
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 317; Journal Issue: 17; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; GLUCOSE; GROWTH FACTORS; HYPERTENSION; IN VITRO; INSULIN; MUSCLES; PATHOGENESIS; PATIENTS; PHOSPHORYLATION; RATS; RECEPTORS; THYMIDINE; TYROSINE

Citation Formats

Liu, Gang, Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang, Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp, Hosomi, Naohisa, Lei, Bai, Nakano, Daisuke, Deguchi, Kazushi, Mori, Hirohito, Masaki, Tsutomu, Ma, Hong, Griendling, Kathy K., and Nishiyama, Akira. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor. United States: N. p., 2011. Web. doi:10.1016/J.YEXCR.2011.07.016.
Liu, Gang, Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang, Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp, Hosomi, Naohisa, Lei, Bai, Nakano, Daisuke, Deguchi, Kazushi, Mori, Hirohito, Masaki, Tsutomu, Ma, Hong, Griendling, Kathy K., & Nishiyama, Akira. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor. United States. doi:10.1016/J.YEXCR.2011.07.016.
Liu, Gang, Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang, Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp, Hosomi, Naohisa, Lei, Bai, Nakano, Daisuke, Deguchi, Kazushi, Mori, Hirohito, Masaki, Tsutomu, Ma, Hong, Griendling, Kathy K., and Nishiyama, Akira. Sat . "Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor". United States. doi:10.1016/J.YEXCR.2011.07.016.
@article{osti_22212177,
title = {Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor},
author = {Liu, Gang and Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang and Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp and Hosomi, Naohisa and Lei, Bai and Nakano, Daisuke and Deguchi, Kazushi and Mori, Hirohito and Masaki, Tsutomu and Ma, Hong and Griendling, Kathy K. and Nishiyama, Akira},
abstractNote = {Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.},
doi = {10.1016/J.YEXCR.2011.07.016},
journal = {Experimental Cell Research},
number = 17,
volume = 317,
place = {United States},
year = {Sat Oct 15 00:00:00 EDT 2011},
month = {Sat Oct 15 00:00:00 EDT 2011}
}