20-Hydroxyeicosatetraenoic Acid (20-HETE): Bioactions, Receptors, Vascular Function, Cardiometabolic Disease and Beyond

Authors

Jonathan V. Pascale, Department of Pharmacology, New York Medical College, Valhalla, NY, United States.
Alexandra Wolf, Department of Pharmacology, New York Medical College, Valhalla, NY, United States.
Yonaton Kadish, School of Medicine, New York Medical College, Valhalla, NY, United States.
Danielle Diegisser, Department of Pharmacology, New York Medical College, Valhalla, NY, United States.
Melissa-Maria Kulaprathazhe, Hunter College, New York, NY, United States.
Danait Yemane, Department of Pharmacology, New York Medical College, Valhalla, NY, United States.
Samir Ali, School of Medicine, New York Medical College, Valhalla, NY, United States.
Namhee Kim, School of Medicine, New York Medical College, Valhalla, NY, United States.
David E. Baruch, School of Medicine, New York Medical College, Valhalla, NY, United States.
Muhamad Afiq Yahaya, Department of Basic Sciences, MAHSA University, Selangor Darul Ehsan, Malaysia; Department of Human Anatomy, Universiti Putra Malaysia (UPM), Selangor Darul Ehsan, Malaysia.
Ercument Dirice, Department of Pharmacology, New York Medical College, Valhalla, NY, United States.
Adeniyi M. Adebesin, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, United States.
John R. Falck, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Michal L. Schwartzman, Department of Pharmacology, New York Medical College, Valhalla, NY, United States.
Victor Garcia, Department of Pharmacology, New York Medical College, Valhalla, NY, United States. Electronic address: victor_garcia@nymc.edu.

Author Type(s)

Student, Faculty

Journal Title

Advances in Pharmacology

First Page

229

Last Page

255

Document Type

Article

Publication Date

1-1-2023

Department

Pharmacology

Abstract

Vascular function is dynamically regulated and dependent on a bevy of cell types and factors that work in concert across the vasculature. The vasoactive eicosanoid, 20-Hydroxyeicosatetraenoic acid (20-HETE) is a key player in this system influencing the sensitivity of the vasculature to constrictor stimuli, regulating endothelial function, and influencing the renin angiotensin system (RAS), as well as being a driver of vascular remodeling independent of blood pressure elevations. Several of these bioactions are accomplished through the ligand-receptor pairing between 20-HETE and its high-affinity receptor, GPR75. This 20-HETE axis is at the root of various vascular pathologies and processes including ischemia induced angiogenesis, arteriogenesis, septic shock, hypertension, atherosclerosis, myocardial infarction and cardiometabolic diseases including diabetes and insulin resistance. Pharmacologically, several preclinical tools have been developed to disrupt the 20-HETE axis including 20-HETE synthesis inhibitors (DDMS and HET0016), synthetic 20-HETE agonist analogues (20-5,14-HEDE and 20-5,14-HEDGE) and 20-HETE receptor blockers (AAA and 20-SOLA). Systemic or cell-specific therapeutic targeting of the 20-HETE-GPR75 axis continues to be an invaluable approach as studies examine the molecular underpinnings activated by 20-HETE under various physiological settings. In particular, the development and characterization of 20-HETE receptor blockers look to be a promising new class of compounds that can provide a considerable benefit to patients suffering from these cardiovascular pathologies.

Recommended Citation

Pascale, J. V., Wolf, A., Kadish, Y., Diegisser, D., Kulaprathazhe, M., Yemane, D., Ali, S., Kim, N., Baruch, D. E., Yahaya, M. A., Dirice, E., Adebesin, A. M., Falck, J. R., Schwartzman, M. L., & Garcia, V. (2023). 20-Hydroxyeicosatetraenoic Acid (20-HETE): Bioactions, Receptors, Vascular Function, Cardiometabolic Disease and Beyond. Advances in Pharmacology, 97, 229-255. https://doi.org/10.1016/bs.apha.2023.01.002