TY - CHAP
T1 - 20-Hydroxyeicosatetraenoic acid (20-HETE)
T2 - Bioactions, receptors, vascular function, cardiometabolic disease and beyond
AU - Pascale, Jonathan V.
AU - Wolf, Alexandra
AU - Kadish, Yonaton
AU - Diegisser, Danielle
AU - Kulaprathazhe, Melissa Maria
AU - Yemane, Danait
AU - Ali, Samir
AU - Kim, Namhee
AU - Baruch, David E.
AU - Yahaya, Muhamad Afiq Faisal
AU - Dirice, Ercument
AU - Adebesin, Adeniyi M.
AU - Falck, John R.
AU - Schwartzman, Michal L.
AU - Garcia, Victor
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - 20-HETE
KW - GPR40
KW - GPR75
KW - Obesity
KW - Vascular function
UR - http://www.scopus.com/inward/record.url?scp=85149879469&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85149879469&partnerID=8YFLogxK
U2 - 10.1016/bs.apha.2023.01.002
DO - 10.1016/bs.apha.2023.01.002
M3 - Chapter
C2 - 37236760
AN - SCOPUS:85149879469
SN - 9780323950572
T3 - Advances in Pharmacology
SP - 229
EP - 255
BT - Bioactive Lipid Mediators in Cardiopulmonary Pharmacology
A2 - Zeldin, Darryl C.
A2 - Seubert, John M.
PB - Academic Press Inc.
ER -