Sirolimus Inhibits Platelet-Derived Growth Factor–Induced Collagen Synthesis in Rat Vascular Smooth Muscle Cells

Park, J.; Ha, Hunjoo; Ahn, Hyung Joon; Kang, Shin Wook; Kim, Y.S.; Seo, Jiyeon; Kim, M.S.

doi:10.1016/j.transproceed.2005.09.066

Cited by 19 publications

(16 citation statements)

References 14 publications

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“…Mammalian target of rapamycin (mTOR) inhibitor (Sehgal, 2003;Granville et al, 2006) Blocking of the synthesis of fibrillin-1 (Schaefer et al, 2007); blocking of HA accumulation (Gouëffic et al, 2007); inhibition of growth factor induced collagen synthesis (Park et al, 2005) Tacrolimus Calcineurin inhibitor (Nghiem et al, 2002) Suppression of cytokine stimulated MMP synthesis (Migita et al, 2005); stimulation of collagen synthesis in vascular smooth muscle cells via TGF-␤ signaling (Giordano et al, 2008) Microbial drugs Doxycycline…”

Section: Sirolimus/ Rapamycinmentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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Section: Sirolimus/ Rapamycinmentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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“…Inflammatory cells likely play a major role in positive remodeling because of their production of metalloproteinases. 30 However, other inflammatory stimuli such as platelet-derived growth factor-induced connective tissue hyper- plasia and collagen synthesis [31][32][33] may be responsible for the opposite process of vessel constriction observed Ͼ3 years after heart transplantation. 16 In that respect, it is important to note that sirolimus is a powerful inhibitor of platelet-derived growth factor-induced proliferation 32 and collagen synthesis, 33 delaying constriction on one hand, but it enhances the expression of interstitial metalloproteinases, accelerating positive remodeling on the other.…”

Section: Pathophysiology Of Vessel Remodelingmentioning

confidence: 99%

“…These differences did not reach statistical significance (Pϭ0.15) but are intriguing in the context of the known antiproliferative properties of sirolimus. 19,32,33 It is important to stress that because of the lack of randomization, small number of events, and retrospective nature of our analysis, the differences in survival should be interpreted cautiously and that prospective clinical trials are required to prove whether sirolimus indeed improves longterm survival in heart transplant patients.…”

Section: Effects Of Sirolimus As Primary Immunosuppression On Cav-relmentioning

confidence: 99%

Sirolimus as Primary Immunosuppression Attenuates Allograft Vasculopathy With Improved Late Survival and Decreased Cardiac Events After Cardiac Transplantation

et al. 2012

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Background-We retrospectively analyzed the potential of sirolimus as a primary immunosuppressant in the long-term attenuation of cardiac allograft vasculopathy progression and the effects on cardiac-related morbidity and mortality. Methods and Results-Forty-five cardiac transplant recipients were converted to sirolimus 1.2 years (0.2, 4.0) after transplantation with complete calcineurin inhibitor withdrawal. Fifty-eight control subjects 2.0 years (0.2, 6.5 years) from transplantation were maintained on calcineurin inhibitors. Age, sex, ejection fraction, and time from transplantation to baseline intravascular ultrasound study were not different (PϾ0.2 for all) between the groups; neither were secondary immunosuppressants and use of steroids. Three-dimensional intravascular ultrasound studies were performed at baseline and 3.

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“…However, more recent work has cast doubt upon the conclusion that true PDGF-mediated proliferation is ROS-dependent. Rapamycin, a relatively new immunosuppressant that acts on the protein synthesis mediator mTOR, inhibits PDGF-induced proliferation without affecting ROS production (Park et al 2005). Furthermore, although PDGF-induced migration is inhibited by the novel Nox inhibitor VAS2870, this inhibitor has no effect on DNA synthesis (Ten Freyhaus et al 2006).…”

Section: Vascular Smooth Muscle Proliferationmentioning

confidence: 99%

Basic Mechanisms of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Injury

Papaharalambus

Griendling

2007

Trends in Cardiovascular Medicine

290

224

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The development of vascular disease has its origins in an initial insult to the vessel wall by biological or mechanical factors. The disruption of homeostatic mechanisms leads to alteration of the original architecture of the vessel and its biological responsiveness, contributing to acute or chronic diseases such as stroke, hypertension and atherosclerosis. Endothelial dysfunction, macrophage infiltration of the vessel wall, and proliferation and migration of smooth muscle cells all involve different types of reactive oxygen species, produced by various vessel wall components. Although basic science and animal research have clearly established the role of reactive oxygen species in the progression of vascular disease, the failure of clinical trials with antioxidant compounds has underscored the need for better antioxidant therapies and a more thorough understanding of the role of reactive oxygen species in cardiovascular physiology and pathology.The fundamental processes underlying the development of vascular diseases such as atherosclerosis, restenosis and hypertensive vascular remodeling have their origins in an initial insult to the vessel wall. Such an insult may arise from mechanical disruption that occurs during percutaneous coronary angioplasty or at regions of oscillatory shear stress, or it can result from biological causes, such as hypercholesterolemia, excess free radicals, diabetes, increased concentrations of plasma homocysteine, or infectious agents. Injury promotes disruption of the homeostatic mechanisms of the endothelial protective barrier, changing its natural properties, increasing its adhesiveness to leukocytes and altering its permeability. This endothelial dysfunction also leads to the formation of vasoactive molecules, which in turn induce inflammatory genes, inactivate nitric oxide (NO • ) and its protective functions, and activate matrix metalloproteinases, leading to extracellular matrix remodeling, and increased smooth muscle cell (VSMC) growth, migration and proliferation. Each of these processes contributes to thickening of the vessel wall or the formation of lesions that can lead to hypertension, acute myocardial infarction and stroke. Reactive Oxygen Species and Vascular InjuryIn the past decade a staggering amount of evidence implicates a common denominator, reactive oxygen species (ROS), in the development of most cardiovascular diseases (Figure 1). Superoxide (O 2 •− ) and hydrogen peroxide (H 2 O 2 ) are two of the most biologically important ROS in the cardiovascular system, and are produced in vascular cells by a number of oxidases, including the NADPH oxidases (Nox) and xanthine oxidase, lipoxygenases, cytochrome p450,

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Sirolimus Inhibits Platelet-Derived Growth Factor–Induced Collagen Synthesis in Rat Vascular Smooth Muscle Cells

Cited by 19 publications

References 14 publications

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

Sirolimus as Primary Immunosuppression Attenuates Allograft Vasculopathy With Improved Late Survival and Decreased Cardiac Events After Cardiac Transplantation

Basic Mechanisms of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Injury

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