Clopidogrel Protects Endothelium by Hindering TNFα-Induced VCAM-1 Expression through CaMKKβ/AMPK/Nrf2 Pathway

Journal of Diabetes Research
Huabing YangShiliu Tian

Abstract

Clopidogrel (INN), an oral antiplatelet drug, has been revealed to have a number of biological properties, for instance, anti-inflammation and antioxidation. Oxidative stress plays an imperative role in inflammation, diabetes mellitus, atherosclerosis, and cancer. In the present study, human aortic endothelial cells (HAECs) were employed to explore the anti-inflammatory activity of INN. INN reduced TNFα-induced reactive oxygen species (ROS) generation and time-dependently prompted the expression and activity of heme oxygenase 1 (HO-1). Cellular glutathione (GSH) levels were augmented by INN. shHO-1 blocked the INN suppression of TNFα-induced HL-60 cell adhesion. The CaMKKβ/AMPK pathway and Nrf2 transcriptional factor were implicated in the induction of HO-1 by INN. Additionally, TNFα dramatically augmented VCAM-1 expression at protein and mRNA levels. INN treatment strikingly repressed TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Compound C, an AMPK inhibitor, and shNrf2 abolished TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Our data suggest that INN diminishes TNFα-stimulated VCAM-1 expression at least in part via HO-1 induction, which is CaMKKβ/AMPK pathway-dependent.

References

Apr 1, 1987·Diabetes/metabolism Reviews·K PyöräläM Uusitupa
Nov 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·M D Maines, A Kappas
Jul 1, 1996·American Journal of Respiratory Cell and Molecular Biology·A M Choi, J Alam
Dec 20, 2002·Nature·Peter Libby
May 13, 2003·Journal of Atherosclerosis and Thrombosis·Jianglin Fan, Teruo Watanabe
Jul 29, 2004·The Annals of Pharmacotherapy·Diana VishnevetskyPritesh J Gandhi
Sep 4, 2004·Antioxidants & Redox Signaling·Giovanni ScapagniniVittorio Calabrese
Jun 1, 2005·Trends in Pharmacological Sciences·Chi Chen, Ah-Ng Tony Kong
Dec 17, 2005·Antioxidants & Redox Signaling·Guoxiang ShenAh-Ng Tony Kong
Aug 22, 2006·Biochimica Et Biophysica Acta·Sanchayita Mitra, Edward Abraham
Aug 2, 2007·Journal of Cardiovascular Pharmacology·Yong Sook KimJung Chaee Kang
Mar 8, 2008·Pharmacological Reviews·Nader G Abraham, Attallah Kappas
May 16, 2009·The Biochemical Journal·Sergio L Colombo, Salvador Moncada
Aug 12, 2009·Free Radical Biology & Medicine·Smadar LevyHenry Jay Forman
Sep 19, 2009·Methods in Molecular Biology·Arthur Millius, Orion D Weiner
Mar 30, 2010·The American Journal of Cardiology·John A McClungNader G Abraham
Oct 7, 2010·Journal of Diabetes·Yi Shi, Paul Michel Vanhoutte
Nov 3, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Xiao-ming LiuWilliam Durante
Apr 21, 2012·International Journal of Hypertension·Kazunobu IshikawaAldons J Lusis
Jan 24, 2014·BioMed Research International·Najah R HadiHussam H Sahib

❮ Previous
Next ❯

Citations

Jun 1, 2019·Journal of Inflammation·Juan LiHayato Iwase
Jan 22, 2019·Current Medicinal Chemistry·Anastasios TentolourisNikolaos Tentolouris
Nov 7, 2017·Oxidative Medicine and Cellular Longevity·Sandro SattaStephen J White
Apr 11, 2020·Advanced Drug Delivery Reviews·Dong NiuGeorge M Church

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
Protein Assay
Fluorescence
nuclear translocation

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Cell Adhesion Molecules in AS

Cell adhesion molecules expressed on the vascular endothelium and circulating leukocytes in response to inflammatory stimuli are implicated in atherosclerosis. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Cardiovascular Inflammation

Inflammation plays a significant role in the development of cardiovascular diseases, an understanding of these endogenous processes is critical for evaluating the risks and potential treatment strategies. Discover the latest research on cardiovascular inflammation here.

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.