Isoform distribution and tissue contents of contractile and cytoskeletal proteins in hypertrophied smooth muscle from rat portal vein.

Malmqvist, Ulf; Arner, Anders

doi:10.1161/01.res.66.3.832

Cited by 56 publications

(42 citation statements)

References 54 publications

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“…In 7 days, this treatment approximately doubles the amount of smooth muscle in the vessel wall, with a corresponding increase in force generation (21). Tissue concentrations of myosin and actin are essentially unaltered after hypertrophy, and thus the total amounts of these contractile proteins increase during hypertrophy in proportion to tissue mass (22). Figure 1C shows 2D gels of a normal and a hypertrophied portal vein.…”

Section: Resultsmentioning

confidence: 98%

Stretch-induced contractile differentiation of vascular smooth muscle: sensitivity to actin polymerization inhibitors

Zeidan

Nordström

Albinsson

et al. 2003

American Journal of Physiology-Cell Physiology

133

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January 29, 2003; 10.1152/ajpcell.00508.2002Signaling mechanisms for stretch-dependent growth and differentiation of vascular smooth muscle were investigated in mechanically loaded rat portal veins in organ culture. Stretch-dependent protein synthesis was found to depend on endogenous release of angiotensin II. Autoradiography after [ 35 S]methionine incorporation revealed stretch-dependent synthesis of several proteins, of which SM22 and actin were particularly prominent. Inhibition of RhoA activity by cellpermeant C3 toxin increased tissue mechanical compliance and reduced stretch-dependent extracellular signal-regulated kinase (ERK)1/2 activation, growth, and synthesis of actin and SM22, suggesting a role of the actin cytoskeleton. In contrast, inhibition of Rho-associated kinase by Y-27632 did not reduce ERK1/2 phosphorylation or actin and SM22 synthesis and did not affect tissue mechanical compliance but still inhibited overall growth. The actin polymerization inhibitors latrunculin B and cytochalasin D both inhibited growth and caused increased tissue compliance. Whereas latrunculin B concentration-dependently reduced actin and SM22 synthesis, cytochalasin D did so at low (10 Ϫ8 M) but not at high (10 Ϫ6 M) concentration. The results show that stretch stabilizes the contractile smooth muscle phenotype. Stretch-dependent differentiation marker expression requires an intact cytoskeleton for stretch sensing, control of protein expression via the level of unpolymerized G-actin, or both.SM22; cytoskeleton; rat portal vein; RhoA; hypertension THE MECHANICAL STRESS IMPOSED on the vascular wall by the intraluminal blood pressure is critical for regulating its growth and phenotypic differentiation, as shown by a massive body of experimental and clinical evidence. The contractile phenotype of the smooth muscle cells in the vessel media, characterized by contractile ability and little tendency to proliferation, is marked by the expression of several smooth muscle-specific proteins, including among others SM22, calponin, hcaldesmon, ␣-actin, and smooth muscle myosin heavy chain (27). These are decreased in cell culture and in cells reacting to injury and inflammatory mediators in the early atherosclerotic process (28). Understanding of the mechanisms maintaining cellular differentiation and of the influence on them by mechanical stress may thus clarify processes involved not only in hypertension but also in the development of atherosclerotic lesions, as well as suggest new approaches for preventing vascular disease.Veins are exposed to lower intraluminal pressure than arteries but show considerable pressure-induced growth, as demonstrated by the hypertrophy, and often rapidly progressing atherosclerosis, of venous grafts exposed to arterial pressure (30). One vessel that has been extensively investigated is the rat portal vein, in which elevated intraluminal pressure in vivo over a few days causes hypertrophy and increased contractility (16, 21). In vitro, portal venous strips kept in organ culture under an applied l...

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Section: Resultsmentioning

confidence: 98%

Stretch-induced contractile differentiation of vascular smooth muscle: sensitivity to actin polymerization inhibitors

Zeidan

Nordström

Albinsson

et al. 2003

American Journal of Physiology-Cell Physiology

133

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“…The portal vein is a low-pressure vessel that rapidly hypertrophies under increased transmural pressure, as shown in rat portal hypertension in vivo (26). The hypertrophy particularly affects the longitudinal muscle layer, which dominates in the portal vein, suggesting that in this intraabdominal vessel the major direction of wall stress is longitudinal.…”

mentioning

confidence: 88%

Integration of signal pathways for stretch-dependent growth and differentiation in vascular smooth muscle

Albinsson¹,

Hellstrand²

2007

American Journal of Physiology-Cell Physiology

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Albinsson S, Hellstrand P. Integration of signal pathways for stretch-dependent growth and differentiation in vascular smooth muscle. Am J Physiol Cell Physiol 293: C772-C782, 2007. First published May 16, 2007; doi:10.1152/ajpcell.00622.2006.-The vascular smooth muscle phenotype is regulated by environmental factors, such as mechanical forces, that exert effects on signaling to differentiation and growth. We used the mouse portal vein in organ culture to investigate stretch-dependent activation of Akt, ERK, and focal adhesion kinase (FAK), which have been suggested to be involved in the regulation of stretch-dependent protein synthesis. The role of actin polymerization in these signaling events was examined using the actin-stabilizing agent jasplakinolide. Stretch caused a biphasic activation of FAK at 5-15 min and 24 -72 h, which may reflect first a direct phosphorylation of preexisting focal adhesions followed by a rearrangement of focal adhesions to accommodate for the increased mechanical load. Phosphorylation of ERK was increased by acute stretch but then decreased, and Akt did not have a distinct peak in stretch-induced phosphorylation. Inhibition of ERK, phosphatidylinositol 3-kinase, or mammalian target of rapamycin reduced global but not contractile protein synthesis with maintained stretch sensitivity. Stabilization of actin filaments with jasplakinolide, in unstretched portal veins, resulted in increased ERK phosphorylation and global protein synthesis as well as the synthesis of contractile proteins. In contrast, stretch during culture with jasplakinolide did not affect FAK phosphorylation or contractility. Therefore, remodeling of smooth muscle cells to adapt to stretch requires a dynamic cytoskeleton. actin polymerization; mitogen-activated protein kinase; phosphatidylinositol 3-kinase; focal adhesion kinase; protein synthesis STRETCH OF THE BLOOD VESSEL WALL by intraluminal pressure stimulates growth and remodeling to compensate for the increased wall tension, such that the tissue stress (force per cross-sectional area) is essentially normalized (23). Growth under these conditions occurs with smooth muscle cells maintained in a contractile phenotype, which differs from the growth pattern seen in vascular lesions, where smooth muscle cells migrate and proliferate after modulation to a synthetic phenotype (5). Although the use of isolated smooth muscle cells stretched on a flexible membrane has provided substantial insights into the mechanisms of smooth muscle cell biomechanics and phenotype regulation, the mechanisms of stretchdependent signaling are probably not identical to those in intact tissue. The use of organ culture of vascular smooth muscle combines the three-dimensional environment of the cells with the advantages of an in vitro condition.The portal vein is a low-pressure vessel that rapidly hypertrophies under increased transmural pressure, as shown in rat portal hypertension in vivo (26). The hypertrophy particularly affects the longitudinal muscle layer, which dominates in the portal ...

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“…After 48 hours, strips in organ culture were exposed for 24 hours to [methyl- 3 H]thymidine or L- [4, H]leucine (Amersham) at activities of 0.2 or 1 Ci/mL, respectively. Incorporation was determined as described.…”

Section: Assay Of Dna and Protein Synthesismentioning

confidence: 99%

“…Partial ligation of the rat portal vein close to its entrance into the liver hilus causes increased pressure and, within 5 to 7 days, increased contractility and marked hypertrophy of the smooth muscle layer, with increased contractile and cytoskeletal protein contents. 2,3 For elucidating mechanisms behind vascular adaptation and growth, in vitro culture offers an advantage in terms of experimental control, but it has proven difficult to maintain isolated smooth muscle cells in the contractile phenotype characteristic of the medial layer of the adult vessel wall. Cyclic stretch of smooth muscle cells grown on elastic media increases the proliferation rate as well as protein synthesis.…”

mentioning

confidence: 99%

Stretch-Dependent Modulation of Contractility and Growth in Smooth Muscle of Rat Portal Vein

Zeidan

Nordström

Dreja

et al. 2000

Circulation Research

106

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Abstract-Increased intraluminal pressure of the rat portal vein in vivo causes hypertrophy and altered contractility in 1 to 7 days. We have used organ cultures to investigate mechanisms involved in this adaptation to mechanical load. Strips of rat portal vein were cultured for 3 days, either undistended or loaded by a weight. Length-force relations were shifted toward longer length in stretched cultured veins compared with freshly dissected veins, whereas the length-force relations of unstretched cultured veins were shifted in the opposite direction. This occurred after culture either with or without 10% FCS to promote growth. The wet weight of loaded veins increased by 56% in the presence of FCS, whereas that of undistended control veins increased by 24%. No weight increase was seen in serum-free culture. The dry/wet weight ratio decreased during culture with FCS but was not affected by stretch. Electron microscopy revealed increased cell cross-sectional area in stretched relative to unstretched veins, and protein contents were greater, as were

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Isoform distribution and tissue contents of contractile and cytoskeletal proteins in hypertrophied smooth muscle from rat portal vein.

Cited by 56 publications

References 54 publications

Stretch-induced contractile differentiation of vascular smooth muscle: sensitivity to actin polymerization inhibitors

Stretch-induced contractile differentiation of vascular smooth muscle: sensitivity to actin polymerization inhibitors

Integration of signal pathways for stretch-dependent growth and differentiation in vascular smooth muscle

Stretch-Dependent Modulation of Contractility and Growth in Smooth Muscle of Rat Portal Vein

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