Category: Lipids/CV Health

Monitor: 32

32 - DIFFERENTIAL EFFECTS OF COX2 INHIBITORS ON THE UNFOLDED PROTEIN RESPONSE IN PRIMARY HUMAN CORONARY ARTERY ENDOTHELIAL CELLS.

Friday, Apr 26
11:30 AM – 12:00 PM

Objective :

COX2 is a key enzyme regulating the conversion of arachidonic acid to PGE2and PGI2. Its activity regulates renal hemodynamics, inflammation, and endothelial thromboresistance. However, long-term rofecoxib use increases the risk of developing coronary artery disease. Since the unfolded protein response (UPR) is involved in atherogenesis, we examined the effects of COX2 inhibitors on endoplasmic reticulum (ER) stress in primary human coronary artery endothelial cells. 


Methods : ER stress was measured in HCAEC treated with either tunicamycin (TM) or high-dextrose using the ER stress secreted alkaline phosphatase (ES-TRAP) assay. Activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1a(IRE1a), phospho-IRE1a, protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), and phospho-PERK were measured by Western blot. 


Results : Treatment of HCAEC with TM and high-dextrose increased ER stress in HCAEC as measured with the ES-TRAP assay. Treatment of cells exposed to TM or high-dextrose with celecoxib, meloxicam, ibuprofen, and acetylsalicylic acid resulted in a dose-dependent decrease in ER stress. However, rofecoxib had no effect on ER stress in cells treated with TM or high-dextrose. High-dextrose and TM increased IRE1aand PERK phosphorylation and ATF6 and GRP78 expression. Treatment with celecoxib, but not rofecoxib, inhibited IRE1aand PERK phosphorylation as well as ATF6 and GRP78 expression.  


Discussion : Treatment with select COX2 inhibitors suppressed the UPR, as indicated using both activity assays and markers for ER stress. 


Conclusion : Our results suggest that select COX2 inhibitors may be safer for long-term use due to their unique ability to inhibit ER stress.  

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Priyanka Bikkina

Fellow
University of Florida Jacksonville
Jacksonville, Florida

University of Michigan B.S Completion in 2009. American University of Antigua MD completion in 2014. 2006-2008: Research assistant, Department of Pathology at University of Michigan. 2008-2009: Research assistant, The Molecular and Behavioral Neuroscience Institute, University of Michigan. 2009- Research assistant , Department of psychology at University of Michigan. Dean's Grant for study of Effect of Vitamin D Deficiency on ER/Oxidative stress in Type 2 Diabetes: Inhibition by statins.

Marie Angelica Landicho

Endocrinology Fellow
University of Florida College of Medicine - Jacksonville
Jacksonville, Florida

Ateneo de Manila University (Quezon City, Philippines), B. S., Completion in 2007
University of Santo Tomas (Manila, Philippines), M. D., Completion in 2011
2011-2012 Postgraduate Internship Training, University of Santo Tomas Hospital (Manila, Philippines)
2014-2017 Internal Medicine Residency, Monmouth Medical Center (Long Branch, New Jersey)
2017-present Endocrinology Fellowship, University of Florida College of Medicine – Jacksonville (Jacksonville, Florida)

Luisa Onstead-Haas

Research Assistant
Mayo Clinic, Florida

Department of Health Sciences Research at Mayo Clinic. Regulation of apolipoprotein A-I gene expression by the histamine H1 receptor: Requirement for NF-κB. Article Jul 2018. Inhibition of hepatic apolipoprotein A-I gene expression by histamine
Article Jan 2018. The Effects of Known Cardioprotective Drugs on Proinflammatory Cytokine Secretion From Human Coronary Artery Endothelial Cells Article Nov 2017

Michael J. Haas

Research Associate Professor of Medicine
University of Florida Jacksonville

B.S. from University of Missouri 1995. Ph.D. from University of Nebraska Medical Center, Omaha. Postdoctoral from University of Wisconsin-Madison. 1991-1995, Post-doctoral research, McArdle Cancer Research Laboratory, University of Wisoconsin - Madison.
1995-1998, Research Associate, McArdle Cancer Research Laboratory, University of Wisconsin – Madison.
1998-2004, Assistant Research Professor, Saint Louis University, Department of Internal Medicine, Division of Endocrinology.
2004-2007, Associate Research Professor, Saint Louis University, Department of Internal Medicine, Division of Endocrinology.
2007-present, Associate Research Professor, University of Florida – Jacksonville, Department of Medicine, Division of Endocrinology.

Arshag Mooradian

Chair, Department of Medicine
University of Florida College of Medicine - Jacksonville

Medical Education: American University of Beirut, New York, NY, USA
Residency: Internal Medicine, American University of Beirut, New York, NY, USA
Fellowship: Endocrinology, Diabetes and Metabolism, University of Minnesota Medical School, Minneapolis, MN, USA

Priyanka Bikkina

Fellow
University of Florida Jacksonville
Jacksonville, Florida

University of Michigan B.S Completion in 2009. American University of Antigua MD completion in 2014. 2006-2008: Research assistant, Department of Pathology at University of Michigan. 2008-2009: Research assistant, The Molecular and Behavioral Neuroscience Institute, University of Michigan. 2009- Research assistant , Department of psychology at University of Michigan. Dean's Grant for study of Effect of Vitamin D Deficiency on ER/Oxidative stress in Type 2 Diabetes: Inhibition by statins.