دورية أكاديمية
أعرض في EDS

The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS signaling and vascular function.

التفاصيل البيبلوغرافية
العنوان: The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS signaling and vascular function.
المؤلفون: Alghanem AF; Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, United States.; Eastern Region, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Al Hasa, Saudi Arabia., Abello J; Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, United States., Maurer JM; Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, United States., Kumar A; Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, United States., Ta CM; Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, United States., Gunasekar SK; Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, United States., Fatima U; Department of Internal Medicine, Cardiovascular Division, University of Iowa, Iowa City, United States., Kang C; Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, United States., Xie L; Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, United States., Adeola O; Department of Internal Medicine, Cardiovascular Division, University of Iowa, Iowa City, United States., Riker M; Department of Ophthalmology, University of Iowa, Carver College of Medicine, Iowa City, United States., Elliot-Hudson M; Department of Internal Medicine, Cardiovascular Division, University of Iowa, Iowa City, United States., Minerath RA; Department of Internal Medicine, Cardiovascular Division, University of Iowa, Iowa City, United States., Grueter CE; Department of Internal Medicine, Cardiovascular Division, University of Iowa, Iowa City, United States., Mullins RF; Department of Ophthalmology, University of Iowa, Carver College of Medicine, Iowa City, United States., Stratman AN; Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, United States., Sah R; Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, United States.; Center for Cardiovascular Research, Washington University, St Louis, United States.
المصدر: ELife [Elife] 2021 Feb 25; Vol. 10. Date of Electronic Publication: 2021 Feb 25.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Endothelium/*physiology , Membrane Proteins/*genetics , Nitric Oxide Synthase Type III/*genetics , Proto-Oncogene Proteins c-akt/*genetics, Animals ; Female ; Male ; Membrane Proteins/metabolism ; Mice ; Nitric Oxide Synthase Type III/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction
مستخلص: The endothelium responds to numerous chemical and mechanical factors in regulating vascular tone, blood pressure, and blood flow. The endothelial volume-regulated anion channel (VRAC) has been proposed to be mechanosensitive and thereby sense fluid flow and hydrostatic pressure to regulate vascular function. Here, we show that the leucine-rich repeat-containing protein 8a, LRRC8A (SWELL1), is required for VRAC in human umbilical vein endothelial cells (HUVECs). Endothelial LRRC8A regulates AKT-endothelial nitric oxide synthase (eNOS) signaling under basal, stretch, and shear-flow stimulation, forms a GRB2-Cav1-eNOS signaling complex, and is required for endothelial cell alignment to laminar shear flow. Endothelium-restricted Lrrc8a KO mice develop hypertension in response to chronic angiotensin-II infusion and exhibit impaired retinal blood flow with both diffuse and focal blood vessel narrowing in the setting of type 2 diabetes (T2D). These data demonstrate that LRRC8A regulates AKT-eNOS in endothelium and is required for maintaining vascular function, particularly in the setting of T2D.
Competing Interests: AA, JA, JM, AK, CT, SG, UF, CK, LX, OA, MR, ME, RM, CG, RM, AS, RS No competing interests declared
(© 2021, Alghanem et al.)
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معلومات مُعتمدة: I01 BX005072 United States BX BLRD VA; R01 DK106009 United States DK NIDDK NIH HHS; R01 HL125436 United States HL NHLBI NIH HHS; R00 HL125683 United States HL NHLBI NIH HHS; T32 HL007752 United States HL NHLBI NIH HHS; R35 GM137976 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: cell biology; diabetes; hypertension; ion channel; mechanobiology; mouse
سلسلة جزيئية: GEO GSE166989
المشرفين على المادة: 0 (LRRC8A protein, mouse)
0 (Membrane Proteins)
EC 1.14.13.39 (Nitric Oxide Synthase Type III)
EC 1.14.13.39 (Nos3 protein, mouse)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
تواريخ الأحداث: Date Created: 20210225 Date Completed: 20220128 Latest Revision: 20220223
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC7997661
DOI: 10.7554/eLife.61313
PMID: 33629656
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.61313