Cardiovascular Endocrinology

SUN-263 - A Protective Role for Endocannabinoids in Preventing Oxidative Stress in HCAEC

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Location: ENDOExpo; Poster Floor

Abstract Poster Presenter(s)

NG

Nidhi Garg, MBBS MD

Resident
Baylor Scott and White
Temple, TX, United States

Co-Author(s)

KC

Kareen Champagne, MD

Fellow
University of Florida Jacksonville
Jacksonville, Florida, United States
AV

Andrew Velarde, None

Undergraduate Student
University of Florida Jacksonville
Jacksonville, Florida, United States
MC

Maurice Chakour, None

Undergraduate Student
University of Florida Jacksonville
Jacksonville, Florida, United States
GZ

George Zakour, BS

Volunteer
University of Florida Jacksonville
Jacksonville, Florida, United States
AA

Anocens Augustin, None

Volunteer
University of Florida Jacksonville
Jacksonville, Florida, United States
JA

Johny Alrahal, MD

Resident
University of Florida Jacksonville
Jacksonville, Florida, United States

Senior Author/Primary Investigator(s)

AM

Arshag D. Mooradian, MD

Chair, Department of Medicine
University of Florida
Jacksonville, Florida, United States

Disclosure(s):

Nidhi Garg, MBBS MD: No financial relationships to disclose

Excess oxidative and endoplasmic reticulum (ER) stress disrupt cellular homeostasis and promote cardiovascular disease (CVD). The endocannabinoids anandamide and 2-arachadonyl glycerol and the potent cannabinoid delta-9-tetrahydrocannabinol increase oxidative stress and ER stress in endothelial cells. However, it remains unclear whether endocannabinoids have intrinsic capacity to ameliorate oxidative stress. In human coronary artery endothelial cells (HCAEC), anandamide, 2-arachadonyl glycerol, and tunicamycin increased superoxide generation and nuclear factor erythroid 2-related factor 2 (NRF2) mRNA and NRF2-dependent reporter gene activity. Furthermore, anandamide increased NRF2-responsive hemeoxygenase 1 (HO1), thioredoxin reductase 1 (TRX1), and NAD(P)H dehydrogenase quinone 1 (NQO1) mRNA. This effect was mediated via protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK); PERK silencing suppressed NRF2 induction by anandamide and tunicamycin. In contrast, activating transcription factor 6 (ATF6) and inositol requiring enzyme 1alpha (IRE1alpha silencing had no effect on NRF2 mRNA or NRF2 target gene expression in tunicamycin and anandamide-treated cells. Likewise, the PERK inhibitor GSK2606414 prevented NRF2 induction by anandamide and tunicamycin while treatment with Ceapin A7 (an ATF6 inhibitor) or GSK2850163 (an IRE1alpha inhibitor) did not. In conclusion, endocannabinoid related ER stress augments production of antioxidant enzymes thereby highlighting the cross talk between ER stress and oxidative stress.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*