scholarly journals The Effects of Elastic Fiber Protein Insufficiency and Treatment on the Modulus of Arterial Smooth Muscle Cells

2014 ◽  
Vol 136 (2) ◽  
Author(s):  
M. Gabriela Espinosa ◽  
William S. Gardner ◽  
Lisa Bennett ◽  
Bradley A. Sather ◽  
Hiromi Yanagisawa ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Elastic Fiber ◽  
Muscle Cells ◽  
Elastic Fibers ◽  
Force Microscopy ◽  
Altered Gene Expression ◽  
Atomic Force ◽  
Fiber Protein ◽  
Altered Gene

Elastic fibers are critical for the mechanical function of the large arteries. Mechanical effects of elastic fiber protein deficiency have been investigated in whole arteries, but not in isolated smooth muscle cells (SMCs). The elastic moduli of SMCs from elastin (Eln-/-) and fibulin-4 (Fbln4-/-) knockout mice were measured using atomic force microscopy. Compared to control SMCs, the modulus of Eln-/- SMCs is reduced by 40%, but is unchanged in Fbln4-/- SMCs. The Eln-/- SMC modulus is rescued by soluble or α elastin treatment. Altered gene expression, specifically of calponin, suggests that SMC phenotypic modulation may be responsible for the modulus changes.

Mechanical properties of the interaction between fibronectin and α5β1-integrin on vascular smooth muscle cells studied using atomic force microscopy

2005 ◽  
Vol 289 (6) ◽  
pp. H2526-H2535 ◽  
Author(s):  
Zhe Sun ◽  
Luis A. Martinez-Lemus ◽  
Andreea Trache ◽  
Jerome P. Trzeciakowski ◽  
George E. Davis ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Atomic Force Microscopy ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Focal Contact ◽  
Force Microscopy ◽  
Atomic Force

The mechanical properties of integrin-extracellular matrix (ECM) interactions are important for the mechanotransduction of vascular smooth muscle cells (VSMC), a process that is associated with focal adhesions, and can be of particular significance in cardiovascular disease. In this study, we characterized the unbinding force and binding activity of the initial fibronectin (FN)-α5β1 interaction on the surface of VSMC using atomic force microscopy (AFM). It is postulated that these initial binding events are important to the subsequent focal adhesion assembly. FN-VSMC adhesions were selectively blocked by antibodies against α5- and β1-integrins as well as RGD-containing peptides but not by antibodies against α4- and β3-integrins, indicating that FN primarily bound to α5β1. A characteristic unbinding force of 39 ± 8 pN was observed and interpreted to represent the FN-α5β1 single-bond strength. The ability of FN to adhere to VSMC (binding probability) was significantly reduced by integrin antagonists, serum starvation, and platelet-derived growth factor (PDGF)-BB, whereas lysophosphatidic acid (LPA) increased FN binding. However, no significant change in the resolved unbinding force was observed. After engagement, the force required to dislodge the FN-coated bead from VSMC increased with increasing of contact time, suggesting a time-dependent increase in number of adhesions and/or altered binding affinity. LPA enhanced this process, whereas PDGF reduced it, suggesting that these factors also affect the multimolecular process of focal contact assembly. Thus AFM is a powerful tool for the characterization of the mechanical properties of integrin-ECM interactions and their regulation. Our results indicate that the functional activity of α5β1 and focal contact assembly can be rapidly regulated.

scholarly journals Stiffness of vascular smooth muscle cells from monkeys studied using atomic force microscopy

2020 ◽  
Author(s):  
Yi Zhu
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Mechanical Forces ◽  
Force Microscopy ◽  
Atomic Force ◽  
Significant Difference ◽  
Cellular Components

Vascular smooth muscle cells (VSMC) are the main cellular components of blood vessel walls and bear external mechanical forces caused by blood flow and pressure. In this report, we have verified the following hypothesis through experiments: The increase in VSMC stiffness may be mainly due to changes in vascular stiffness due to aging. Although aging enhances the stiffness and adhesion of VSMC, there is no significant difference in apparent elastic modulus and adhesion between the VSMC obtained by male and female. The effect of aging through the ECM-integrin-cytoskeleton axis is related to increased VSMC stiffness and matrix adhesion rather than gender.

P1937Deficiency of PI 3-kinase isoform p110alpha in smooth muscle cells impairs vascular integrity and promotes aortic aneurysm formation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Vantler ◽  
E M Berghausen ◽  
M Zierden ◽  
M Mollenhauer ◽  
D Mehrkens ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Inflammation ◽  
Elastic Fiber ◽  
Muscle Cells ◽  
Aortic Aneurysms ◽  
Elastic Fibers ◽  
Infrarenal Aorta ◽  
Vascular Integrity ◽  
Anti Inflammatory

Abstract Background The pathobiology of aortic aneurysms is characterized by vascular inflammation, extracellular matrix degeneration, and particularly by loss and dedifferentiation of vascular smooth muscle cells (SMCs). In SMCs, the PI 3-kinase isoform p110α mediates receptor tyrosine kinase dependent proliferation, chemotaxis, and survival. Smooth muscle specific p110α deficient mice (SM-p110α−/− mice) display reduced medial wall thickness, substantially reduced neointima formation and media hypertrophy after balloon injury of the carotid artery. Objective We hypothesized that loss of p110α signaling impairs vascular integrity and promotes development and progression of abdominal aortic aneurysms (AAA). We aimed to elucidate the impact of p110α deficiency on vascular integrity, SMC phenotypic modulation, vascular inflammation, and AAA formation. Methods and results Ultra-structural characterization of aortic wall morphology in abdominal aortas from SM-p110α−/− mice by transmission electron microscopy (TEM) revealed disarranged structure of tunica media as indicated by disorganized elastic fibers, detached SMCs, and elastic fiber breaks. Western blots showed reduced elastin and fibrillin expression in SMCs from p110α−/− mice. Media thickness was significantly reduced in abdominal aortas from SM-p110α−/− mice compared to wild type (WT) controls (29.0±3.1 vs. 42.5±4.1 μm). Lack of p110α decreased expression of differentiation markers SM-α-actin and SM-MHC. p110α deficiency significantly diminished responsiveness of aortic rings to vasodilator acetylcholine. These data indicate loss of differentiation and impaired contractility of p110α−/− SMCs. We subjected SM-p110α−/− mice and WT littermate controls to the porcine pancreatic elastase (PPE) model of AAA. PPE was infused into the infrarenal aorta, respectively, to induce AAA formation. Ultrasonic examination of abdominal aortas demonstrated an enlarged aortic diameter in PPE challenged mice. AAA formation was significantly (p<0.01) enhanced in SM-p110α−/− (0.46±0.12 mm, n=8) compared to SM-p110α+/+ mice (0.18±0.03 mm, n=4). These data indicate a protective function of p110α in AAA formation. Immunocytochemistry of the aortic medial compartment from PPE-perfused SM-p110α−/− mice revealed significantly increased MOMA-2+ monocyte/macrophage content indicating augmented aortic inflammation during AAA formation compared to WT controls. Furthermore, SMCs from SM-p110α−/− mice expressed reduced amounts of anti-inflammatory angiopoietin1 compared to p110α+/+ SMCs. Moreover, frequent apoptotic/necrotic SMCs were found in the aortic media of SM-p110α−/− mice by TEM, potentially contributing to vascular inflammation in a critical fashion. Conclusion These data indicate that p110α signaling critically contributes to vascular integrity via maintaining SMC plasticity, elastic fiber homeostasis, and anti-inflammatory processes. Consequently, lack of proper p110α signaling promotes progression of AAA formation.

scholarly journals The deregulation of STIM1 and store operative calcium entry impaired aortic smooth muscle cells contractility in aortic medial degeneration

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Junmou Hong ◽  
Zhipeng Hu ◽  
Qi Wu ◽  
Chaoliang Tang ◽  
Junxia Hu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Er Stress ◽  
Elastic Fiber ◽  
Muscle Cells ◽  
Cytoplasmic Calcium ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Medial Degeneration ◽  
Related Proteins

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.

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