The deregulation of STIM1 and store operative calcium entry impaired aortic smooth muscle cells contractility in aortic medial degeneration
Authors: Qi Wu
Bowen Li
Chaoliang Tang
Zhiwei Wang
Zhipeng Hu
Junxia Hu
Ruoshi Chen
Junmou Hong
Journal: Bioscience reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: STIM1; aortic smooth muscle cells; endoplasmic reticulum stress; transforming growth factor β1.
Affiliations: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China., Department of Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China., Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Provence, China., Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China .

Abstract:  Background: Microarray analysis of clinical aortic samples suggested a potential role for stromal interaction molecule 1 (STIM1) in the modulation of aortic medial degeneration (AMD), despite the uncertainty about STIM1 in normal aortic smooth muscle cells (ASMCs). Here, we aimed to explore changes in STIM1 expression in AMD, and the possible mechanisms. Methods: An AMD model was established using auto-delivery of angiotensin II (Ang II) into ApoE-/- mice. We assessed the effects of SKF96365, a STIM1 inhibitor, in AMD model and in vitro cultured ASMCs. Elastic van Gieson (EVG) staining was used to visualize elastic fiber injury. Mitochondria changes were viewed by TEM. Cytoplasmic calcium was quantified by measuring fluo-4 staining in a flow cytometer. Mechanical stretching device was used to mimic stretching that ASMCs experience in vivo Cell apoptosis was determined by using Annexin V/propidium iodide (PI) staining. The expression of STIM1, contractile related proteins (α-smooth muscle actin (α-SMA), myosin light chain (MLC)), endoplasmic reticulum (ER) stress-related proteins (CHOP, activating transcription factor 6 (ATF-6)) and smad2/3 were assessed by Western blotting, immunohistochemistry (IHC), and immunofluorescence (IF). Results: SKF96365 exacerbated aortic injury in the AMD model. SKF96365 reduced cytoplasmic calcium concentration in ASMCs, caused mitochondrial swelling, and elevated the expression of ATF-6 and CHOP. SKF96365 decreased the expression of MLC and α-SMA in ASMCs, causing them to be vulnerable to mechanical stretch. SKF96365 suppressed smad2/3 activation after treatment with transforming growth factor (TGF) β1 (TGFβ1). Conclusions: STIM1 is indispensable in ASMCs. Interfering with STIM1 exaggerated the AMD process by modulating the expression of contractile proteins, inducing ER stress in ASMCs. 

Retracted: No

PubPeer comments:
 Two images in figure 3D appear to overlap. *** ![file] *** ![file] , 
 https: doi.org 10.1042 BSR-20181504_COR The authors of the original paper u201cThe deregulation of STIM1 and store operative calcium entry (SOCE) impaired aortic smooth muscle cells contractility in aortic medial degenerationu201d (Biosci Rep. (2019), 39(1), DOI: 10.1042 BSR20181504), would like to provide the following correction statement: The picture in Figure 3D was replaced by a new set of images. ![file] ,