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

Zeidan, Asad; Nordström, Ina; Dreja, Karl; Malmqvist, Ulf; Hellstrand, Per

doi:10.1161/01.res.87.3.228

Cited by 57 publications

(113 citation statements)

References 32 publications

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“…In vascular smooth muscle of KO mice, Cav-2 is also largely absent, Cav-3 is substantially reduced, and no caveolae structures are observed (4,24). We have previously reported that physiological stretch stimulates protein synthesis in the portal vein and that activation of ERK1/2 is a mediator of this effect (3,30). ERK1/2 activation is rapid and transient with a peak at about 5 min following the onset of stretch, correlating with rapid activation of FAK (2).…”

Section: Resultsmentioning

confidence: 98%

“…E and F: flow-induced Akt (E) and ERK1/2 (F) phosphorylation of carotid arteries, relative to unstimulated contralateral control arteries, were evaluated following 15 min of ϳ19 dyn/cm 2 shear stress (n ϭ 4). *P Ͻ 0.05. course of organ culture, which is found also in the rat portal vein (30), is unclear, but one possible explanation is reorganization of the actin cytoskeleton to accommodate the applied force and normalize tissue stress (2). Differing contents of Cav-1 following culture could not explain this decrease.…”

Section: Discussionmentioning

confidence: 95%

“…Stretch also stimulates growth of the portal vein via an increase in ERK1/2 phosphorylation, partly depending on an endogenous release of angiotensin II and endothelin-1 (28,30). Stretch-induced ERK1/2 activation and growth of the portal vein are sensitive to extraction of cholesterol, which disrupts membrane microdomains, such as lipid rafts and caveolae (28).…”

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confidence: 99%

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Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall

Albinsson¹,

Nordström²,

Swärd³

et al. 2008

American Journal of Physiology-Cell Physiology

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The role of caveolae in stretch- versus flow-induced vascular responses was investigated using caveolin 1-deficient [knockout (KO)] mice. Portal veins were stretched longitudinally for 5 min (acute) or 72 h (organ culture). Basal ERK1/2 and Akt phosphorylation were increased in organ-cultured KO veins, as were protein synthesis and vessel wall cross sections. Stretch stimulated acute phosphorylation of ERK1/2 and long-term phosphorylation of focal adhesion kinase (FAK) and cofilin but did not affect Akt phosphorylation. Protein synthesis, and particularly synthesis of smooth muscle differentiation markers, was increased by stretch. These effects did not differ in portal veins from KO and control mice, which also showed the same contractile response to membrane depolarization and inhibition by the Rho kinase inhibitor Y-27632. KO carotid arteries had increased wall cross sections and responded to pressurization (120 mmHg) for 1 h with increased ERK1/2 but not Akt phosphorylation, similar to control arteries. Shear stress by flow for 15 min, on the other hand, increased phosphorylation of Akt in carotids from control but not KO mice. In conclusion, caveolin 1 contributes to low basal ERK1/2 and Akt activity and is required for Akt-dependent signals in response to shear stress (flow) but is not essential for trophic effects of stretch (pressure) in the vascular wall.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

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Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall

Albinsson¹,

Nordström²,

Swärd³

et al. 2008

American Journal of Physiology-Cell Physiology

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“…1 The concentrations listed in table 1 are all given in mM, whereas in the referenced articles they are often given in μmole/(g fresh weight), μmole/(g dry weight) or μmole/(g protein). In order to have all those concentrations in mM, we collected values that gave us an idea of the converting factors: we used literature values for the ratio dry weight/fresh weight [55,3,23,36,5,49,9,45,52], cell volumes [34,43,39,13,47,40,7,33], and values for the ratio cytoplasm volume/dry weight [45]. Even though these values were determined for different organisms, the average should be a good approximation.…”

Section: The Steady State Hypothesis and Parameters Of The Modelmentioning

confidence: 99%

Mitochondrial energetic metabolism: A simplified model of TCA cycle with ATP production

Nazaret

Heiske

Thurley

et al. 2009

Journal of Theoretical Biology

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Mitochondria play a central role in cellular energetic metabolism. The essential parts of this metabolism are the Tricarboxyl-acid (TCA) cycle, the respiratory chain and the Adenosine Tri-Phosphate (ATP) synthesis machinery. Here a simplified model of these three metabolic components with a limited set of differential equations is presented. The existence of a steady state is demonstrated and results of numerical simulations are presented. The relevance of a simple model to represent actual in vivo behavior is discussed.

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“…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 load developed increased contractility, protein synthesis, and cell cross-sectional area compared with unloaded control strips (40). This model thus allows investigation of the effect of stretch on the pattern of protein expression and its relationship to contractile differentiation.…”

mentioning

confidence: 99%

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

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

Cited by 57 publications

References 32 publications

Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall

Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall

Mitochondrial energetic metabolism: A simplified model of TCA cycle with ATP production

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

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