Stretch-dependent growth and differentiation in vascular smooth muscle: role of the actin cytoskeleton

2005 ◽  
Vol 83 (10) ◽  
pp. 869-875 ◽  
Author(s):  
Per Hellstrand ◽  
Sebastian Albinsson
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Actin Polymerization ◽  
Muscle Cells ◽  
Intraluminal Pressure ◽  
Marker Genes ◽  
Signal Pathways ◽  
Differentiation Markers ◽  
Contractile Phenotype

The smooth muscle cells in the vascular wall are constantly exposed to distending forces from the intraluminal pressure. A rise in blood pressure triggers growth of the vessel wall, which is characterized primarily by hypertrophy of smooth muscle cells with maintained differentiation in a contractile phenotype. Growth factor stimulation of dissociated smooth muscle cells, on the other hand, causes proliferative growth with loss of contractility. This type of response is also found in neointima development following angioplasty and in atherosclerotic lesions. An intact tissue environment is therefore critical for preserved differentiation. Recent advances point to a role of actin polymerization in the expression of smooth muscle differentiation marker genes, in concert with serum response factor (SRF) and cofactors, such as myocardin. Stretch of intact venous smooth muscle activates Rho and inhibits the actin filament severing factor cofilin, resulting in increased actin polymerization. Concomitantly, the rates of synthesis of SRF-regulated differentiation markers, such as SM22α, calponin, and α-actin, are increased. This increase in differentiation signals is parallel with activation of the mitogen-activated protein (MAP) kinase pathway. Thus stretch-induced growth in a maintained contractile phenotype occurs by dual activation of signal pathways regulating both growth and differentiation. A current challenge is to identify sites of crosstalk between these pathways in intact smooth muscle tissue.Key words: stretch, hypertension, ERK, Rho, caveolae.

scholarly journals Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction

2008 ◽  
Vol 295 (3) ◽  
pp. C576-C587 ◽  
Author(s):  
Susan J. Gunst ◽  
Wenwu Zhang
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Actin Polymerization ◽  
Muscle Cells ◽  
Smooth Muscle Contraction ◽  
Mechanical Tension ◽  
Muscle Tissues ◽  
Cytoskeletal Dynamics

A growing body of data supports a view of the actin cytoskeleton of smooth muscle cells as a dynamic structure that plays an integral role in regulating the development of mechanical tension and the material properties of smooth muscle tissues. The increase in the proportion of filamentous actin that occurs in response to the stimulation of smooth muscle cells and the essential role of stimulus-induced actin polymerization and cytoskeletal dynamics in the generation of mechanical tension has been convincingly documented in many smooth muscle tissues and cells using a wide variety of experimental approaches. Most of the evidence suggests that the functional role of actin polymerization during contraction is distinct and separately regulated from the actomyosin cross-bridge cycling process. The molecular basis for the regulation of actin polymerization and its physiological roles may vary in diverse types of smooth muscle cells and tissues. However, current evidence supports a model for smooth muscle contraction in which contractile stimulation initiates the assembly of cytoskeletal/extracellular matrix adhesion complex proteins at the membrane, and proteins within this complex orchestrate the polymerization and organization of a submembranous network of actin filaments. This cytoskeletal network may serve to strengthen the membrane for the transmission of force generated by the contractile apparatus to the extracellular matrix, and to enable the adaptation of smooth muscle cells to mechanical stresses. Better understanding of the physiological function of these dynamic cytoskeletal processes in smooth muscle may provide important insights into the physiological regulation of smooth muscle tissues.

Role of ET-1 receptor binding and [Ca2+]i in contraction of coronary arteries from DOCA-salt hypertensive rats

2002 ◽  
Vol 282 (5) ◽  
pp. H1944-H1949 ◽  
Author(s):  
Ararat D. Giulumian ◽  
Mariela M. Molero ◽  
Vikram B. Reddy ◽  
Jennifer S. Pollock ◽  
David M. Pollock ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Receptor Binding ◽  
Muscle Cells ◽  
Intraluminal Pressure ◽  
Endothelin Receptor ◽  
Hypertensive Rats ◽  
Small Arteries

Hypertension is associated with an increase in coronary artery disease, but little is known about the regulation of coronary vascular tone by endothelin-1 (ET-1) in hypertension. The present study evaluated the mechanisms mediating altered contraction to ET-1 in coronary small arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. DOCA-salt rats exhibited an increase in systolic blood pressure and plasma ET-1 levels compared with placebo rats. Contraction to ET-1 (1 × 10−11 to 3 × 10−8 M), measured in isolated coronary small arteries maintained at a constant intraluminal pressure of 40 mmHg, was largely reduced in vessels from DOCA-salt rats compared with placebo rats. To determine the role of endothelin receptor binding in the impaired contraction to ET-1,125I-labeled ET-1 receptor binding was measured in membranes isolated from coronary small arteries. Maximum binding (fmol/mg protein) and binding affinity were similar in coronary membranes from DOCA-salt rats compared with placebo rats. Changes in intracellular Ca2+ concentration ([Ca2+]i) were measured in freshly dissociated coronary small artery smooth muscle cells loaded with fura 2. ET-1 (10−9 M) produced a 30 ± 9% increase in [Ca2+]i in smooth muscle cells from placebo rats, but had no effect on cells from DOCA-salt rats (2 ± 2%). In summary, the ET-1-induced coronary artery contraction and increase in [Ca2+]i are impaired in DOCA-salt hypertensive rats, whereas endothelin receptor binding is not altered. These results suggest endothelin receptor uncoupling from signaling mechanisms and indicate that impaired [Ca2+]isignaling contributes to the decrease in ET-1-induced contraction of coronary small arteries in DOCA-salt hypertensive rats.

scholarly journals Abl regulates smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 activation

2012 ◽  
Vol 302 (7) ◽  
pp. C1026-C1034 ◽  
Author(s):  
Li Jia ◽  
Ruping Wang ◽  
Dale D. Tang
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Actin Polymerization ◽  
Muscle Cells ◽  
Smooth Muscle Cell Proliferation ◽  
Actin Dynamics

Abl is a nonreceptor tyrosine kinase that has a role in regulating migration and adhesion of nonmuscle cells as well as smooth muscle contraction. The role of Abl in smooth muscle cell proliferation has not been investigated. In this study, treatment with endothelin-1 (ET-1) and platelet-derived growth factor (PDGF) increased Abl phosphorylation at Tyr412 (an indication of Abl activation) in vascular smooth muscle cells. To assess the role of Abl in smooth muscle cell proliferation, we generated stable Abl knockdown cells by using lentivirus-mediated RNA interference. ET-1- and PDGF-induced cell proliferation was attenuated in Abl knockdown cells compared with cells expressing control shRNA and uninfected cells. Abl silencing also arrested cell cycle progression from G0/G1 to S phase. Furthermore, activation of smooth muscle cells with ET-1 and PDGF induced phosphorylation of ERK1/2 and Akt. Abl knockdown attenuated ERK1/2 phosphorylation in smooth muscle cells stimulated with ET-1 and PDGF. However, Akt phosphorylation upon stimulation with ET-1 and PDGF was not reduced. Because Abl is known to regulate actin polymerization in smooth muscle, we also evaluated the effects of inhibition of actin polymerization on phosphorylation of ERK1/2. Pretreatment with the actin polymerization inhibitor latrunculin-A also blocked ERK1/2 phosphorylation during activation with ET-1 and PDGF. The results suggest that Abl may regulate smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 phosphorylation during mitogenic activation.

The role of WNT/b-catenin signaling in smooth muscle cells during lung development and repair

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
A Moiseenko ◽  
E El Agha ◽  
B MacKenzie ◽  
S De Langhe ◽  
S Bellusci
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Lung Development ◽  
Muscle Cells
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