Enhanced oxygen uptake and lactate production of smooth muscle cell proliferates of rabbit carotid arteries

1980 ◽  
Vol 387 (1) ◽  
pp. 73-77 ◽  
Author(s):  
H. E. Knehr ◽  
H. Heinle ◽  
E. Betz
Keyword(s):  
Smooth Muscle ◽  
Oxygen Uptake ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Carotid Arteries ◽  
Lactate Production

scholarly journals An essential role of PDCD4 in vascular smooth muscle cell apoptosis and proliferation: implications for vascular disease

2010 ◽  
Vol 298 (6) ◽  
pp. C1481-C1488 ◽  
Author(s):  
Xiaojun Liu ◽  
Yunhui Cheng ◽  
Jian Yang ◽  
Thomas J. Krall ◽  
Yuqing Huo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Carotid Arteries ◽  
Vascular Diseases ◽  
Vsmc Proliferation ◽  
Vascular Walls

It is well established that vascular smooth muscle cell (VSMC) apoptosis and proliferation are critical cellular events in a variety of human vascular diseases. However, the molecular mechanisms involved in controlling VSMC apoptosis and proliferation are still unclear. In the current study, we have found that programmed cell death 4 (PDCD4) is significantly downregulated in balloon-injured rat carotid arteries in vivo and in platelet-derived growth factor-stimulated VSMCs in vitro. Overexpression of PDCD4 via adenovirus (Ad-PDCD4) increases VSMC apoptosis in an apoptotic model induced by serum deprivation. In contrast, VSMC apoptosis is significantly decreased by knockdown of PDCD4 via its small interfering RNA. In the rat carotid arteries in vivo, VSMC apoptosis is increased by Ad-PDCD4. We have further identified that activator protein 1 is a downstream signaling molecule of PDCD4 that is associated with PDCD4-mediated effects on VSMC apoptosis. In addition, VSMC proliferation was inhibited by overexpression of PDCD4. The current study has identified, for the first time, that PDCD4 is an essential regulator of VSMC apoptosis and proliferation. The downregulation of PDCD4 expression in diseased vascular walls may be responsible for the imbalance of VSMC proliferation and apoptosis. The results indicate that PDCD4 may be a new therapeutic target in proliferative vascular diseases.

Changes in Vascular Viscoelasticity Caused by Smooth Muscle Cell Tone and Pressurization Frequency

2007 ◽  
Author(s):  
Ryan J. DeWall ◽  
Naomi C. Chesler
Keyword(s):  
Smooth Muscle ◽  
Energy Dissipation ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Function ◽  
Viscoelastic Properties ◽  
Carotid Arteries ◽  
The Body ◽  
Thromboxane Receptor

The cushioning and conduit functions of large arteries allow the body to efficiently circulate blood and perfuse organs. These functions can be characterized by quantifying the viscoelastic properties of arteries. In this study, we investigated the effects of smooth muscle cell (SMC) tone and pressurization frequency on vascular viscoelasticity using an isolated, perfused vessel test. We tested mouse carotid arteries in control, dilated (via sodium nitroprusside) and constricted (via the thromboxane receptor analogue U46619) states at 0.1, 1, 3, and 5 Hz with a pulse pressure from 90 to 120 mmHg. Dose response experiments were first performed in order to determine the optimal vasoconstrictor concentration to be used in frequency response experiments. Our results showed that energy dissipation was significantly higher and elasticity was significantly lower for vasoconstricted arteries. We also found that frequency significantly changed both energy dissipation and elasticity as the frequency was increased from 0.1 to 5 Hz. These results provide insights into the changes in vascular viscoelasticity caused by SMC tone and pressurization frequency, which have implications for vascular function in vivo.

Mechanisms of vascular preservation by a novel NO donor following rat carotid artery intimal injury

1995 ◽  
Vol 269 (3) ◽  
pp. H1122-H1131 ◽  
Author(s):  
J. P. Guo ◽  
M. M. Panday ◽  
P. M. Consigny ◽  
A. M. Lefer
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Carboxylic Acid ◽  
Carotid Artery ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Carotid Arteries ◽  
Smooth Muscle Cell Proliferation ◽  
No Donor ◽  
Intimal Injury

We studied the effects of a novel organic nitric oxide (NO) donor, 4-hydroxymethyl-furazan-3-carboxylic acid-2-oxide (CAS-1609), in a rat carotid artery intimal injury model. The NO donor, CAS-1609, or its non-NO-donating control compound, 4-hydroxymethyl-furazan-3-carboxylic acid (C-93-4845), was infused intravenously at 30 micrograms/day. Seven days after injury, carotid artery rings contracted only 56 +/- 6 mg to NG-nitro-L-arginine methyl ester in C-93-4845-treated rats, compared with 120 +/- 17 mg in CAS-1609-treated rats (P < 0.02), indicating a preservation of endogenous NO release. Improved responses to the endothelium-dependent dilator, acetylcholine, also occurred in injured arteries treated with CAS-1609. Morphometric analysis of injured carotid arteries given the inactive compound showed marked intimal thickening with an intimal-to-medial ratio (I/M) of 0.76 +/- 0.02, compared with a significantly lower I/M of 0.32 +/- 0.04 (P < 0.01) in injured carotid arteries given CAS-1609. Additionally, CAS-1609 was found to have a concentration-dependent stimulatory effect on cultured rat aortic endothelial cell proliferation (P < 0.01) but and inhibitory effect on platelet-derived growth factor-BB (10 ng/ml)-stimulated rat aortic smooth muscle cell proliferation (P < 0.01). This is the first study to demonstrate that NO plays a dual role in vascular cell proliferation, stimulating endothelial cells but inhibiting smooth muscle cell proliferation. This dual effect of NO on cell proliferation is associated with an in vivo reduction in neointimal thickening and an acceleration of endothelial recovery determined by both anatomic and functional methods.

scholarly journals Pulmonary artery smooth muscle cell hyperproliferation and metabolic shift triggered by pulmonary overcirculation

2016 ◽  
Vol 311 (4) ◽  
pp. H944-H957 ◽  
Author(s):  
Jason Boehme ◽  
Xutong Sun ◽  
Kathryn V. Tormos ◽  
Wenhui Gong ◽  
Manuela Kellner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Lactate Production ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Glycolytic Flux ◽  
Pulmonary Artery Smooth Muscle

Vascular cell hyperproliferation and metabolic reprogramming contribute to the pathophysiology of pulmonary arterial hypertension (PAH). An important cause of PAH in children with congenital heart disease (CHD) is increased pulmonary blood flow (PBF). To better characterize this disease course we studied early changes in pulmonary artery smooth muscle cell (PASMC) proliferation and metabolism using a unique ovine model of pulmonary overcirculation. Consistent with PAH in adults, PASMCs derived from 4-wk-old lambs exposed to increased PBF (shunt) exhibited increased rates of proliferation. While shunt PASMCs also exhibited significant decreases in mitochondrial oxygen consumption, membrane potential, and tricarboxylic acid (TCA) cycle function, suggesting a switch to Warburg metabolism as observed in advanced PAH in adults, they unexpectedly demonstrated decreased glycolytic lactate production, likely due to enhanced flux through the pentose phosphate pathway (PPP). This may be a response to the marked increase in NADPH oxidase (Nox) activity and decreased NADPH/NADP+ ratios observed in shunt PASMCs. Consistent with these findings, pharmacological inhibition of Nox activity preferentially slowed the growth of shunt PASMCs in vitro. Our results therefore indicate that PASMC hyperproliferation is observed early in the setting of pulmonary overcirculation and is accompanied by a unique metabolic profile that is independent of HIF-1α, PDHK1, or increased glycolytic flux. Our results also suggest that Nox inhibition may help prevent pulmonary overcirculation-induced PAH in children born with CHD.

Expression of granulocyte colony-stimulating factor is induced in injured rat carotid arteries and mediates vascular smooth muscle cell migration

2005 ◽  
Vol 288 (1) ◽  
pp. C81-C88 ◽  
Author(s):  
Xing Chen ◽  
Sheri E. Kelemen ◽  
Michael V. Autieri
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Balloon Angioplasty ◽  
Carotid Arteries ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Important Mediator ◽  
Stimulating Factor

Granulocyte colony-stimulating factor (G-CSF) is a lineage-restricted hematopoietic growth factor that stimulates proliferation and maturation of hematopoietic progenitors and is a known powerful mobilizer of bone marrow-derived stem cells. Very little has been reported on G-CSF expression and modulation of vascular smooth muscle cell (VSMC) activation. The purpose of this study was to characterize the expression and effects of G-CSF on primary human VSMC and balloon angioplasty-injured rat carotid arteries. In cultured human VSMC, G-CSF mRNA and protein expression are induced by several cytokines, with the most potent being fetal calf serum and T-lymphocyte-conditioned media. G-CSF is not expressed in naive rat carotid arteries but is induced in neointimal SMC in carotid arteries subject to balloon angioplasty. G-CSF is chemotactic for human VSMC. There is a significant difference between unstimulated cells and those treated with G-CSF at 100 and 1,000 pg/ml ( P < 0.01 and 0.05 for 3 experiments). G-CSF also activates the GTPase Rac1, a regulator of cellular migration in VSMC. Inhibition of Rac1 inhibits G-CSF-driven VSMC migration. Important signal transduction protein kinases, including p44/42 MAPK, Akt, and S6 kinase, are also activated in response to G-CSF. This is the first report describing the expression of G-CSF in injured arteries and the multiple effects of G-CSF on VSMC activation. Together, our data suggest that G-CSF is an important mediator of inflammatory cell-VSMC communication and VSMC autocrine activation and may be an important mediator of the VSMC response to injury.

scholarly journals Trypanosoma cruzi Infection Induces Proliferation of Vascular Smooth Muscle Cells

2006 ◽  
Vol 74 (1) ◽  
pp. 152-159 ◽  
Author(s):  
Ghada S. Hassan ◽  
Shankar Mukherjee ◽  
Fnu Nagajyothi ◽  
Louis M. Weiss ◽  
Stefka B. Petkova ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Cyclin D1 ◽  
Muscle Cell ◽  
Carotid Arteries ◽  
Umbilical Vein ◽  
Muscle Cells ◽  
Caveolin 1 ◽  
Endothelin 1

ABSTRACT Trypanosoma cruzi infection causes cardiomyopathy and vasculopathy. Previous studies have demonstrated that infection of human umbilical vein endothelial and smooth muscle cells resulted in activation of extracellular signal-regulated kinase (ERK). In the present study, smooth muscle cells were infected with trypomastigotes, and immunoblot analysis revealed an increase in the expression of cyclin D1 and proliferating cell nuclear antigen (PCNA), important mediators of smooth muscle cell proliferation. Interestingly, after infection, the expression of caveolin-1 was reduced in both human umbilical vein endothelial cells and smooth muscle cells. Immunoblot and immunohistochemical analyses of lysates of carotid arteries obtained from infected mice revealed increased expression of PCNA, cyclin D1, its substrate, phospho-Rb (Ser780), and phospho-ERK1/2. The expression of the cyclin-dependent kinase inhibitor p21 Cip1/Waf1 , caveolin-1, and caveolin-3 was reduced in carotid arteries obtained from infected mice. There was an increase in the abundance of pre-pro-endothelin-1 mRNA in the carotid artery and aorta from infected mice. The ETA receptor was also elevated in infected arteries. ERK activates endothelin-1, which in turn exerts positive feedback activating ERK, and cyclin D1 is a downstream target of both endothelin-1 and ERK. There was significant incorporation of bromodeoxyuridine into smooth muscle cell DNA when treatment was with conditioned medium obtained from infected endothelial cells. Taken together, these data suggest that T. cruzi infection stimulates smooth muscle cell proliferation and is likely a result of the upregulation of the ERK-cyclin D1-endothelin-1 pathway.

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