Abstract
The Cytoskeletal Adaptor Protein Sorbs2 Regulate Vascular Contractility Through Smooth Muscle and Endothelial Cell
Physiology (Bethesda, Md.), Vol.40(S1)
05/2025
DOI: 10.1152/physiol.2025.40.S1.1719
Abstract
Abstract only Our research aims to define the mechanisms that the Sorbs2 protein plays in vascular smooth muscle cell (VSMC) contraction. We isolated aortas and carotids from wild-type (WT) and Sorbs2 global knockout (Sorbs2-KO) mice and assessed the role of Sorbs2 in phenylephrine (PE) mediated vasoconstriction, Acetylcholine (Ach) mediated vasodilation, and passive-length tension relationships using wire myography. The data show that aorta from Sorbs2-KO mice have significantly increased PE-induced contractility. Inhibition of endothelial nitric oxide synthase(eNOS) with NG-nitro-L-arginine methyl ester(L-NAME) abolishes the difference, suggesting a potential role in endothelial functions. In Sorbs2-KO carotid ACh-induced vasodilation was inhibited, supporting this idea. Next, to test if Sorbs2 affects calcium-dependent and independent vasoconstriction, we pre-constricted carotids with PE (1E-6 M) and assessed vasodilation using nifedipine, an L-type calcium channel blocker and fasudil, a Rho kinase inhibitor. The data show similar vasodilation between WT and Sorbs2-KO vessels. Passive length-tension relationships were established and measured as a function of length. Data show that Sorbs2-KO arteries are more elastic. Sorbs2 is present as different isoforms in multiple cell types, an experimental limitation in germline deleted Sorbs2 mice. To assess the role of Sorbs2 in VSMC-specific mechanics, the tamoxifen-induced smooth muscle-specific Sorbs2-KO mice (Sorbs2ICRE-KO) was created. Wire myography experiments were repeated with aorta and carotids. Passive length-tension relationships and vasoconstriction, using PE and U46619 – a thromboxane A2 receptor agonist – were assayed. Data show that carotid from Sorbs2ICRE-KO have significantly increased U46619-induced contractility, amplified upon inhibition of eNOS with LNAME. Non-significant increase for PE-induced contraction was observed. This suggests a potential role for Sorbs2 in VSMC as a G-protein coupled receptor (GPCR) scaffolding protein. The passive length-tension relationship shows a non-significant increase in Sorbs2ICRE-KO aorta compliance, potentially due to low sample size(n=4). Altogether, these results suggest that Sorbs2 may regulate VSMC contractility through endothelial functions, GPCR scaffold remodeling, and vessel elasticity through cytoskeletal remodeling. In the future, we plan to assess the specific role of Sorbs2 in endothelial regulation, GPCR scaffolding, and cytoskeletal remodeling through biochemical analysis techniques, and mechanical strain/stress testing. American Heart Association [Grant Number 18690400] This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Details
- Title: Subtitle
- The Cytoskeletal Adaptor Protein Sorbs2 Regulate Vascular Contractility Through Smooth Muscle and Endothelial Cell
- Creators
- Henry Lin - University of IowaGrace RoccoBen Stimson - University of IowaKailey Said - University of IowaConnor Linzer - University of IowaOlha Koval - University of IowaIsabella Grumbach - University of IowaRyan Boudreau - University of IowaJared McLendon - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Physiology (Bethesda, Md.), Vol.40(S1)
- DOI
- 10.1152/physiol.2025.40.S1.1719
- ISSN
- 1548-9213
- eISSN
- 1548-9221
- Publisher
- AMER PHYSIOLOGICAL SOC
- Grant note
- American Heart Association: 18690400
American Heart Association [Grant Number 18690400]
- Language
- English
- Date published
- 05/2025
- Academic Unit
- Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984843247102771
Metrics
1 Record Views