Different Cell Cycle Regulation of Vascular Smooth Muscle in Genetic Hypertension

Tanner, Felix C.; Greutert, Helen; Barandier, Christine; Frischknecht, Karin; Lüscher, Thomas F.

doi:10.1161/01.hyp.0000082360.65547.7c

Cited by 25 publications

(22 citation statements)

References 29 publications

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“…Previous studies have reported vascular smooth muscle hyper-responsiveness in hypertension both under basal conditions as well as after treatment with a range of growth factors (Hamet et al, 1988;Battle et al, 1994;Begum et al, 1998;Tanner et al, 2003). However, these differences in growth rates have been shown to be specific for individual growth factors.…”

Section: Tablementioning

confidence: 99%

The Impact of Blunted β-Adrenergic Responsiveness on Growth Regulatory Pathways in Hypertension

Gros

Ding²,

Chorazyczewski³

et al. 2005

Mol Pharmacol

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The effects of vasodilator hormones acting through receptors linked to adenylyl cyclase are impaired in the hypertensive state. This has been ascribed to impaired receptor-G protein coupling. However, these receptors also act via effectors not linked to adenylyl cyclase activation. These "alternate" mechanisms may be especially important in growth regulation and might be unaffected (or enhanced) with G protein-coupled receptor-G protein uncoupling. Therefore, we assessed the effects of ␤-adrenergic activation on 1) regulation of phosphatidylinositol 3-kinase (PI3 kinase) and extracellular signalregulated kinase (ERK) activation-two tyrosine kinasedependent enzymes linked to cell growth-and 2) microarray analysis in vascular smooth muscle cells from spontaneously hypertensive rats (SHR). Isoproterenol-stimulated phosphorylation of ERK1/2 was impaired in SHR. The effect of forskolin was unaltered. In contrast, both vasopressin and angiotensin 2-mediated stimulation of ERK activation was enhanced in SHR. In addition, ␤-adrenergic-mediated inhibition of PI3 kinase activity was attenuated in SHR (whereas the effect of forskolin remained intact). In microarray studies, the effect of isoproterenol to regulate transcription was significantly impaired in SHR (as was the effect of forskolin). Together, these data support the hypothesis that the blunted vasodilator effects of hormones linked to adenylyl cyclase activation are an index of a more generalized impairment in modulating growth regulatory pathways. Furthermore, this study supports the hypothesis that the blunting of ␤-adrenergic responses relating to increased G protein-coupled receptor kinase 2 expression reflects a "generalized uncoupling" of ␤-adrenergic-mediated responses and do not support the concept of "enhanced coupling" of "alternate" pathways of ␤-adrenergic growth regulatory pathways in the hypertensive state.

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Section: Tablementioning

confidence: 99%

The Impact of Blunted β-Adrenergic Responsiveness on Growth Regulatory Pathways in Hypertension

Gros

Ding²,

Chorazyczewski³

et al. 2005

Mol Pharmacol

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“…Once confluent, cells were synchronised to the same stage of the cell cycle by culturing in serum-free media for 24 h as described previously [30] . Cells were then treated with 0, 5, 25 and 100 M Mb and after 24 h, the coverslips were washed with PBS and prepared for microscopy (below).…”

Section: Renal Cell Transport Studiesmentioning

confidence: 99%

Myoglobin Induces Oxidative Stress and Decreases Endocytosis and Monolayer Permissiveness in Cultured Kidney Epithelial Cells without Affecting Viability

Parry

Ellis²,

Li³

et al. 2008

Kidney Blood Press Res

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Background: Muscle degradation caused by severe burn releases myoglobin (Mb), which accumulates in the kidney (termed myoglobinuria). Mb is a pro-oxidant. Aim: To demonstrate that Mb promotes oxidative stress and dysfunction in cultured Madin-Darby canine kidney type II (MDCK II) cells. Methods: The glutathione redox ratio was used to monitor oxidative stress. Regulation of antioxidant response genes was determined with RT-PCR. Propidium iodide and annexin V staining were markers of necrosis and apoptosis, respectively. Mitochondrial function was assessed by monitoring mitochondrial depolarisation. Endocytosis was determined with immune fluorescence microscopy, and monolayer permeability was monitored with labelled inulin. Results: Kidney epithelial cells exposed to (0–100 µM) Mb showed a dose-dependent decrease in the glutathione redox ratio indicative of enhanced oxidative stress. In parallel, the expression of antioxidant genes for superoxide dismutase (SOD)-1/2, inducible haemoxygenase (HO-1) and catalase (CAT) increased in MDCK II cells, coupled with increases in corresponding activity. Notably, apoptosis and necrosis remained unaffected. However, transferrin endocytosis and monolayer permeability decreased significantly, while clathrin distribution and mitochondrial function were unaffected. Conclusion: Low concentrations of Mb promote oxidative stress in kidney epithelial cells that manifest as subtle changes to function without decreasing viability. Whether this impairs kidney function in burns patients is not clear.

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“…20,21 Cells were grown to confluence in 6-cm culture dishes and rendered quiescent for 24 hours before stimulation with thrombin or tumor necrosis factor (TNF)-␣ (Sigma). Rapamycin, wortmannin (both from Sigma), FK-506 (Alexis), and LY294002 (Cell Signaling) were added to the dishes 60 minutes before stimulation.…”

Section: Cell Culturementioning

confidence: 99%

Rapamycin, but Not FK-506, Increases Endothelial Tissue Factor Expression

et al. 2005

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Background-Drugs released from stents affect the biology of vascular cells. We examined the effect of rapamycin and FK-506 on tissue factor (TF) expression in human aortic endothelial cells (HAECs) and vascular smooth muscle cells (HAVSMCs). Methods and Results-Rapamycin enhanced thrombin-and tumor necrosis factor (TNF)-␣-induced endothelial TF expression in a concentration-dependent manner. The maximal increase was 2.5-fold more pronounced than that by thrombin or TNF-␣ alone and was paralleled by a 1.4-fold higher TF surface activity compared with thrombin alone. Rapamycin by itself increased basal TF levels by 40%. In HAVSMCs, rapamycin did not affect thrombin-or TNF-␣-induced TF expression. In contrast to rapamycin, FK-506 did not enhance thrombin-or TNF-␣-induced endothelial TF expression. Thrombin induced a transient dephosphorylation of the mammalian target of rapamycin downstream target p70S6 kinase. Rapamycin completely abrogated p70S6 kinase phosphorylation, but FK-506 did not. FK-506 antagonized the effect of rapamycin on thrombin-induced TF expression. Rapamycin did not alter the pattern of p38, extracellular signal-regulated kinase, or c-Jun NH 2 -terminal kinase phosphorylation. Real-time polymerase chain reaction analysis revealed that rapamycin had no influence on thrombin-induced TF mRNA levels for up to 2 hours but led to an additional increase after 3 and 5 hours.

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Different Cell Cycle Regulation of Vascular Smooth Muscle in Genetic Hypertension

Cited by 25 publications

References 29 publications

The Impact of Blunted β-Adrenergic Responsiveness on Growth Regulatory Pathways in Hypertension

The Impact of Blunted β-Adrenergic Responsiveness on Growth Regulatory Pathways in Hypertension

Myoglobin Induces Oxidative Stress and Decreases Endocytosis and Monolayer Permissiveness in Cultured Kidney Epithelial Cells without Affecting Viability

Rapamycin, but Not FK-506, Increases Endothelial Tissue Factor Expression

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