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.
Issue Section:
Research Papers
References
1.
Wagenseil
, J. E.
, and Mecham
, R. P.
, 2009
, “Vascular Extracellular Matrix and Arterial Mechanics
,” Physiol. Rev.
, 89
(3
), pp. 957
–989
.10.1152/physrev.00041.20082.
Glagov
, S.
, Vito
, R.
, Giddens
, D. P.
, and Zarins
, C. K.
, 1992
, “Micro-Architecture and Composition of Artery Walls: Relationship to Location, Diameter and the Distribution of Mechanical Stress
,” J. Hypertens. Suppl.
, 10
(6
), pp. S101
–S104
.10.1097/00004872-199207005-000143.
Standley
, P. R.
, Camaratta
, A.
, Nolan
, B. P.
, Purgason
, C. T.
, and Stanley
, M. A.
, 2002
, “Cyclic Stretch Induces Vascular Smooth Muscle Cell Alignment via No Signaling
,” Am. J. Physiol., Heart and Circulatory Physiol.
, 283
(5
), pp. H1907
–H1914
.4.
Wolinsky
, H.
, and Glagov
, S.
, 1967
, “A Lamellar Unit of Aortic Medial Structure and Function in Mammals
,” Circ. Res.
, 20
(1
), pp. 99
–111
.10.1161/01.RES.20.1.995.
Wagenseil
, J. E.
, and Mecham
, R. P.
, 2007
, “New Insights into Elastic Fiber Assembly
,” Birth Defects Res. C Embryo Today
, 81
(4
), pp. 229
–240
.10.1002/bdrc.201116.
Li
, D. Y.
, Brooke
, B.
, Davis
, E. C.
, Mecham
, R. P.
, Sorensen
, L. K.
, Boak
, B. B.
, Eichwald
, E.
, and Keating
, M. T.
, 1998
, “Elastin is an Essential Determinant of Arterial Morphogenesis
,” Nature
, 393
(6682
), pp. 276
–280
.10.1038/305227.
Wagenseil
, J. E.
, Nerurkar
, N. L.
, Knutsen
, R. H.
, Okamoto
, R. J.
, Li
, D. Y.
, and Mecham
, R. P.
, 2005
, “Effects of Elastin Haploinsufficiency on the Mechanical Behavior of Mouse Arteries
,” Am. J. Physiol. Heart Circ. Physiol.
, 289
(3
), pp. H1209
–H1217
.10.1152/ajpheart.00046.20058.
Li
, D. Y.
, Faury
, G.
, Taylor
, D. G.
, Davis
, E. C.
, Boyle
, W. A.
, Mecham
, R. P.
, Stenzel
, P.
, Boak
, B.
, and Keating
, M. T.
, 1998
, “Novel Arterial Pathology in Mice and Humans Hemizygous for Elastin
,” J. Clin. Invest.
, 102
(10
), pp. 1783
–1787
.10.1172/JCI44879.
Li
, D. Y.
, Toland
, A. E.
, Boak
, B. B.
, Atkinson
, D. L.
, Ensing
, G. J.
, Morris
, C. A.
, and Keating
, M. T.
, 1997
, “Elastin Point Mutations Cause an Obstructive Vascular Disease, Supravalvular Aortic Stenosis
,” Human Mol. Genet.
, 6
(7
), pp. 1021
–1028
.10.1093/hmg/6.7.102110.
Mclaughlin
, P. J.
, Chen
, Q.
, Horiguchi
, M.
, Starcher
, B. C.
, Stanton
, J. B.
, Broekelmann
, T. J.
, Marmorstein
, A. D.
, McKay
, B.
, Mecham
, R.
, Nakamura
, T.
, and Marmorstein
, L. Y.
, 2006
, “Targeted Disruption of Fibulin-4 Abolishes Elastogenesis and Causes Perinatal Lethality in Mice
,” Mol. Cell Biol.
, 26
(5
), pp. 1700
–1709
.10.1128/MCB.26.5.1700-1709.200611.
Huang
, J.
, Davis
, E. C.
, Chapman
, S. L.
, Budatha
, M.
, Marmorstein
, L. Y.
, Word
, R. A.
, and Yanagisawa
, H.
, 2010
, “Fibulin-4 Deficiency Results in Ascending Aortic Aneurysms: A Potential Link between Abnormal Smooth Muscle Cell Phenotype and Aneurysm Progression
,” Circ. Res.
, 106
(3
), pp. 583
–592
.10.1161/CIRCRESAHA.109.20785212.
Hucthagowder
, V.
, Sausgruber
, N.
, Kim
, K. H.
, Angle
, B.
, Marmorstein
, L. Y.
, and Urban
, Z.
, 2006
, “Fibulin-4: A Novel Gene for an Autosomal Recessive Cutis Laxa Syndrome
,” Am. J. Human Genet.
, 78
(6
), pp. 1075
–1080
.10.1086/50430413.
Wagenseil
, J. E.
, Ciliberto
, C. H.
, Knutsen
, R. H.
, Levy
, M. A.
, Kovacs
, A.
, and Mecham
, R. P.
, 2009
, “Reduced Vessel Elasticity Alters Cardiovascular Structure and Function in Newborn Mice
,” Circ. Res.
, 104
(10
), pp. 1217
–1224
.10.1161/CIRCRESAHA.108.19205414.
Huang
, J.
, Yamashiro
, Y.
, Papke
, C. L.
, Ikeda
, Y.
, Lin
, Y.
, Patel
, M.
, Inagami
, T.
, Le
, V. P.
, Wagenseil
, J. E.
, and Yanagisawa
, H.
, 2013
, “Angiotensin-Converting Enzyme-Induced Activation of Local Angiotensin Signaling is Required for Ascending Aortic Aneurysms in Fibulin-4-Deficient Mice
,” Sci. Transl. Med.
, 5
(183
), p. 018358
.15.
Martens
, J. C.
, and Radmacher
, M.
, 2008
, “Softening of the Actin Cytoskeleton by Inhibition of Myosin Ii
,” Pflugers Arch.
, 456
(1
), pp. 95
–100
.10.1007/s00424-007-0419-816.
Prabhune
, M.
, Belge
, G.
, Dotzauer
, A.
, Bullerdiek
, J.
, and Radmacher
, M.
, 2012
, “Comparison of Mechanical Properties of Normal and Malignant Thyroid Cells
,” Micron
, 43
(12
), pp. 1267
–1272
.10.1016/j.micron.2012.03.02317.
Qiu
, H.
, Zhu
, Y.
, Sun
, Z.
, Trzeciakowski
, J. P.
, Gansner
, M.
, Depre
, C.
, Resuello
, R. R.
, Natividad
, F. F.
, Hunter
, W. C.
, Genin
, G. M.
, Elson
, E. L.
, Vatner
, D. E.
, Meininger
, G. A.
, and Vatner
, S. F.
, 2010
, “Short Communication: Vascular Smooth Muscle Cell Stiffness as a Mechanism for Increased Aortic Stiffness With Aging
,” Circ. Res.
, 107
(5
), pp. 615
–619
.10.1161/CIRCRESAHA.110.22184618.
Karnik
, S. K.
, Brooke
, B. S.
, Bayes-Genis
, A.
, Sorensen
, L.
, Wythe
, J. D.
, Schwartz
, R. S.
, Keating
, M. T.
, and Li
, D. Y.
, 2003
, “A Critical Role for Elastin Signaling in Vascular Morphogenesis and Disease
,” Development
, 130
(2
), pp. 411
–423
.10.1242/dev.0022319.
Svitkina
, T. M.
, and Parsons
, D. F.
, 1993
, “Binding of Some Metastatic Tumor Cell Lines to Fibrous Elastin and Elastin Peptides
,” Int. J. Cancer
, 53
(5
), pp. 824
–828
.10.1002/ijc.291053052020.
Sun
, Z.
, Martinez-Lemus
, L. A.
, Trache
, A.
, Trzeciakowski
, J. P.
, Davis
, G. E.
, Pohl
, U.
, and Meininger
, G. A.
, 2005
, “Mechanical Properties of the Interaction between Fibronectin and α5β1-Integrin on Vascular Smooth Muscle Cells Studied Using Atomic Force Microscopy
,” Am. J. Physiol. Heart Circ. Physiol.
, 289
(6
), pp. H2526
–H2535
.10.1152/ajpheart.00658.200421.
Sader
, J. E.
, 1995
, “Parallel Beam Approximation for V-Shaped Atomic-Force Microscope Cantilevers
,” Rev. Sci. Instrum.
, 66
(9
), pp. 4583
–4587
.10.1063/1.114529222.
Costa
, K. D.
, 2006
, “Imaging and Probing Cell Mechanical Properties With the Atomic Force Microscope
,” Methods Mol. Biol.
, 319
, pp. 331
–361
.10.1007/978-1-59259-993-623.
Wang
, Z.
, Wang
, D. Z.
, Pipes
, G. C.
, and Olson
, E. N.
, 2003
, “Myocardin Is a Master Regulator of Smooth Muscle Gene Expression
,” Proc. Natl. Acad. Sci. USA
, 100
(12
), pp. 7129
–7134
.10.1073/pnas.123234110024.
Wright
, D. B.
, Trian
, T.
, Siddiqui
, S.
, Pascoe
, C. D.
, Johnson
, J. R.
, Dekkers
, B. G.
, Dakshinamurti
, S.
, Bagchi
, R.
, Burgess
, J. K.
, Kanabar
, V.
, and Ojo
, O. O.
, 2013
, “Phenotype Modulation of Airway Smooth Muscle in Asthma
,” Pulmonary Pharmacol. Therapeutics
, 26
(1
), pp. 42
–49
.10.1016/j.pupt.2012.08.00525.
Stegemann
, J. P.
, Hong
, H.
, and Nerem
, R. M.
, 2005
, “Mechanical, Biochemical, and Extracellular Matrix Effects on Vascular Smooth Muscle Cell Phenotype
,” J. Appl. Physiol.
, 98
(6
), pp. 2321
–2327
.10.1152/japplphysiol.01114.200426.
Han
, M.
, Dong
, L. H.
, Zheng
, B.
, Shi
, J. H.
, Wen
, J. K.
, and Cheng
, Y.
, 2009
, “Smooth Muscle 22 Alpha Maintains the Differentiated Phenotype of Vascular Smooth Muscle Cells by Inducing Filamentous Actin Bundling
,” Life Sci.
, 84
(13–14
), pp. 394
–401
.10.1016/j.lfs.2008.11.01727.
Kuang
, S. Q.
, Kwartler
, C. S.
, Byanova
, K. L.
, Pham
, J.
, Gong
, L.
, Prakash
, S. K.
, Huang
, J.
, Kamm
, K. E.
, Stull
, J. T.
, Sweeney
, H. L.
, and Milewicz
, D. M.
, 2012
, “Rare, Nonsynonymous Variant in the Smooth Muscle-Specific Isoform of Myosin Heavy Chain, Myh11, R247c, Alters Force Generation in the Aorta and Phenotype of Smooth Muscle Cells
,” Circ. Res.
, 110
(11
), pp. 1411
–1422
.10.1161/CIRCRESAHA.111.26174328.
Mayanagi
, T.
, and Sobue
, K.
, 2011
, “Diversification of Caldesmon-Linked Actin Cytoskeleton in Cell Motility
,” Cell Adh. Migr.
, 5
(2
), pp. 150
–159
.10.4161/cam.5.2.1439829.
Lin
, S.
, and Mequanint
, K.
, 2012
, “The Role of Ras-Erk-Il-1beta Signaling Pathway in Upregulation of Elastin Expression by Human Coronary Artery Smooth Muscle Cells Cultured in 3d Scaffolds
,” Biomaterials
, 33
(29
), pp. 7047
–7056
.10.1016/j.biomaterials.2012.06.04430.
Gimona
, M.
, Herzog
, M.
, Vandekerckhove
, J.
, and Small
, J. V.
, 1990
, “Smooth Muscle Specific Expression of Calponin
,” FEBS Lett.
, 274
(1–2
), pp. 159
–162
.10.1016/0014-5793(90)81353-P31.
Menice
, C. B.
, Hulvershorn
, J.
, Adam
, L. P.
, Wang
, C. A.
, and Morgan
, K. G.
, 1997
, “Calponin and Mitogen-Activated Protein Kinase Signaling in Differentiated Vascular Smooth Muscle
,” J. Biol. Chem.
, 272
(40
), pp. 25157
–12561
.10.1074/jbc.272.40.2515732.
Azeloglu
, E. U.
, and Costa
, K. D.
, 2011
, “Atomic Force Microscopy in Mechanobiology: Measuring Microelastic Heterogeneity of Living Cells
,” Methods Mol. Biol.
, 736
, pp. 303
–329
.10.1007/978-1-61779-105-5Copyright © 2014 by ASME
You do not currently have access to this content.
