Endothelin-1 (ET-1)

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
Post Reply
Site Admin
Posts: 5544
Joined: Tue Jan 18, 2005 10:25 pm

Endothelin-1 (ET-1)

Post by admin »

Endothelin-1 (ET-1)
©2022 PFPC

Abraham GR, Kuc RE, Althage M, Greasley PJ, Ambery P, Maguire JJ, Wilkinson IB, Hoole SP, Cheriyan J, Davenport AP - "Endothelin-1 is increased in the plasma of patients hospitalised with Covid-19" J Mol Cell Cardiol 167:92-96 (2022) doi: 10.1016/j.yjmcc.2022.03.007
"Our results demonstrate that elevated ET-1 in the acute phase of Covid-19 infection is a clinical feature unique to severe disease, supporting the hypothesis [8] that endothelin receptor antagonists, used to treat pulmonary arterial hypertension, may be beneficial in a subset of Covid-19 patients."

COVID Vaccination

Ivanko I, Ćelap I, Margetić S, Marijančević D, Josipović J, Gaćina P - "Changes in haemostasis and inflammatory markers after mRNA BNT162b2 and vector Ad26.CoV2.S SARS-CoV-2 vaccination" Thromb Res 228:137-144 (2023). doi: 10.1016/j.thromres.2023.06.008
"In our study, a rise in big ET-1 was noted after mRNA vaccination."


ALERT Jiménez-Córdova MI, González-Horta C, Ayllón-Vergara JC, Arreola-Mendoza L, Aguilar-Madrid G, Villareal-Vega EE, Barrera-Hernández Á, Barbier OC, Del Razo LM - "Evaluation of vascular and kidney injury biomarkers in Mexican children exposed to inorganic fluoride" Environ Res 169:220-228 (2019) doi: 10.1016/j.envres.2018.10.028
https://linkinghub.elsevier.com/retriev ... 18)30388-8
"In robust multiple linear regression models, urinary F was positively associated with eGFR (β = 1.3, p = 0.015), uCys-C (β = -8.5, p = 0.043), VCAM-1 (β = 111.1, p = 0.019), ICAM-1 (β = 57, p = 0.032) and cIMT (β = 0.01, p = 0.032). An inverse association was observed with uCys-C (β = -8.5, p = 0.043) and sCys-C (β = -9.6, p = 0.021), and no significant associations with ET-1 (β = 0.069, p = 0.074) and KIM-1 (β = 29.1, p = 0.212) were found."

Sun L, Gao Y, Zhang W, Liu X, Li B, Cui X, Sun D - "Mechanisms Underlying Endothelin-1 Level Elevations Caused by Excessive Fluoride Exposure" Cell Physiol Biochem 40(5):861-873 (2016).doi: 10.1159/000453145
https://karger.com/cpb/article/40/5/861 ... in-1-Level
"Excessive fluoride exposure leads to characteristic endothelial damage (vacuoles), thoracic aorta hardening, and plasma ET-1 level elevations in rabbits. In addition, the ROS-RAS-MEK1/2-pERK1/2/ERK1/2 pathway plays a crucial—and at least partial—role in ET-1 over-expression, which is promoted by excessive fluoride exposure."


Harada T, Horinouchi T, Higa T, Hoshi A, Higashi T, Terada K, Mai Y, Nepal P, Horiguchi M, Hatate C, Miwa S - "Endothelin-1 activates extracellular signal-regulated kinases 1/2 via transactivation of platelet-derived growth factor receptor in rat L6 myoblasts" Life Sci 104(1-2):24-31 (2014). doi: 10.1016/j.lfs.2014.04.002
"These results suggest that ETAR stimulation induces ERK1/2 phosphorylation in L6 myoblasts through Gq/11 protein-dependent, PLC-independent PDGFR transactivation which requires dynamin-dependent ETAR internalization."

Horinouchi T, Nishimoto A, Nishiya T, Lu L, Kajita E, Miwa S - "Endothelin-1 decreases [Ca2+]i via Na+/Ca2+ exchanger in CHO cells stably expressing endothelin ETA receptor" Eur J Pharmacol 566(1-3):28-33 (2007). doi: 10.1016/j.ejphar.2007.03.019
https://eprints.lib.hokudai.ac.jp/dspac ... 2115/28203
"Stimulation of endothelin ETA receptor with endothelin-1 is generally believed to induce an increase in intracellular Ca2+ concentration ([Ca2+]i) via Gq/11 protein. Here we provide the first convincing evidence that endothelin-1 elicited Gq/11 protein-dependent and -independent ‘decrease’ in [Ca2+]i via Na+/Ca2+ exchanger (NCX) in Chinese hamster ovary (CHO) cells stably expressing human endothelin ETA receptor. In the cells treated with 1 μM thapsigargin, an inhibitor of endoplasmic Ca2+ pump, that induces an increase in [Ca2+]i via capacitative Ca2+ entry, endothelin-1 induced a decrease in [Ca2+]i which was partially inhibited by YM-254890, a specific inhibitor of Gq/11, indicating that Gq/11-dependent and independent pathways are involved in the decrease."

Park-Windhol C, Zhang P, Zhu M, Su J, Chaves L Jr, Maldonado AE, King ME, Rickey L, Cullen D, Mende U - "Gq/11-mediated signaling and hypertrophy in mice with cardiac-specific transgenic expression of regulator of G-protein signaling 2" PLoS One 7(7):e40048 (2012). doi: 10.1371/journal.pone.0040048
"Activation of G(q/11)-mediated signaling is required for pressure overload-induced cardiomyocyte (CM) hypertrophy to develop...Inhibition of endothelin-1-induced G(q/11)-mediated phospholipase C β activity in ventricles and atrial appendages indicated functionality of transgenic RGS2."

Kanai SM, Heffner C, Cox TC, Cunningham ML, Perez FA, Bauer AM, Reigan P, Carter C, Murray SA, Clouthier DE - "Auriculocondylar syndrome 2 results from the dominant-negative action of PLCB4 variants" Dis Model Mech 15(4):dmm049320 (2022). doi: 10.1242/dmm.049320
"PLCB4 is a direct signaling effector of the endothelin receptor type A (EDNRA)-Gq/11 pathway."


Mayyas F, Saadeh N, Al-Muqbel K, Van Wagoner DR - "Plasma endothelin-1 levels are increased in atrial fibrillation patients with hyperthyroidism" PLoS One 13(12):e0208206 (2018). doi: 10.1371/journal.pone.0208206

Gong N, Gao C, Chen X, Wang Y, Tian L - "Adipokine expression and endothelial function in subclinical hypothyroidism rats" Endocr Connect 7(2):295-304 (2018) doi: 10.1530/EC-18-0007

Gamal Y, Badawy A, Ali AM, Farghaly HS, Metwalley KA, Gaber N, Allam MT, Farouk Y - "Endothelial dysfunction in children with newly diagnosed Graves' disease" Eur J Pediatr 182(6):2793-2800 (2023) doi: 10.1007/s00431-023-04919-z


Ahirwar AK, Singh A, Jain A, Patra SK, Goswami B, Bhatnagar MK, Bhattacharjee J - "Raised TSH is associated with endothelial dysfunction in Metabolic Syndrome: A case control study" Rom J Intern Med 55(4):212-221 (2017). doi: 10.1515/rjim-2017-0023

Tian L, Zhang L, Liu J, Guo T, Gao C, Ni J - "Effects of TSH on the function of human umbilical vein endothelial cells" J Mol Endocrinol 52(2):215-22 (2014) doi: 10.1530/JME-13-0119
https://jme.bioscientifica.com/view/jou ... /2/215.xml
Post Reply