scholarly journals Substrate Stiffness and Stretch Regulate Profibrotic Mechanosignaling in Pulmonary Arterial Adventitial Fibroblasts

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1000
Author(s):  
Ariel Wang ◽  
Shulin Cao ◽  
Jennifer C. Stowe ◽  
Daniela Valdez-Jasso
Keyword(s):  
Transforming Growth Factor ◽  
Substrate Stiffness ◽  
Messenger Rnas ◽  
Ang Ii ◽  
Integrin Β3 ◽  
Custom Made ◽  
Adventitial Fibroblasts ◽  
Pulmonary Arterial ◽  
Six Genes

Pulmonary arterial adventitial fibroblasts (PAAFs) are important regulators of fibrotic vascular remodeling during the progression of pulmonary arterial hypertension (PAH), a disease that currently has no effective anti-fibrotic treatments. We conducted in-vitro experiments in PAAFs cultured on hydrogels attached to custom-made equibiaxial stretchers at 10% stretch and substrate stiffnesses representing the mechanical conditions of mild and severe stages of PAH. The expression of collagens α(1)I and α(1)III and elastin messenger RNAs (Col1a1, Col3a1, Eln) were upregulated by increased stretch and substrate stiffness, while lysyl oxidase-like 1 and α-smooth muscle actin messenger RNAs (Loxl1, Acta2) were only significantly upregulated when the cells were grown on matrices with an elevated stiffness representative of mild PAH but not on a stiffness representative of severe PAH. Fibronectin messenger RNA (Fn1) levels were significantly induced by increased substrate stiffness and transiently upregulated by stretch at 4 h, but was not significantly altered by stretch at 24 h. We modified our published computational network model of the signaling pathways that regulate profibrotic gene expression in PAAFs to allow for differential regulation of mechanically-sensitive nodes by stretch and stiffness. When the model was modified so that stiffness activated integrin β3, the Macrophage Stimulating 1 or 2 (MST1\2) kinases, angiotensin II (Ang II), transforming growth factor-β (TGF-β), and syndecan-4, and stretch-regulated integrin β3, MST1\2, Ang II, and the transient receptor potential (TRP) channel, the model correctly predicted the upregulation of all six genes by increased stiffness and the observed responses to stretch in five out of six genes, although it could not replicate the non-monotonic effects of stiffness on Loxl1 and Acta2 expression. Blocking Ang II Receptor Type 1 (AT1R) with losartan in-vitro uncovered an interaction between the effects of stretch and stiffness and angiotensin-independent activation of Fn1 expression by stretch in PAAFs grown on 3-kPa matrices. This novel combination of in-vitro and in-silico models of PAAF profibrotic cell signaling in response to altered mechanical conditions may help identify regulators of vascular adventitial remodeling due to changes in stretch and matrix stiffness that occur during the progression of PAH in-vivo.

Norepinephrine and ANG II stimulate secretion of TGF-beta by neonatal rat cardiac fibroblasts in vitro

1995 ◽  
Vol 268 (4) ◽  
pp. C910-C917 ◽  
Author(s):  
S. A. Fisher ◽  
M. Absher
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Neonatal Rat ◽  
Heart Cells ◽  
Ang Ii ◽  
Tgf Beta ◽  
Hypertrophic Growth ◽  
Beta 2

Transforming growth factor-beta (TGF-beta) is a ubiquitous growth-regulating protein that is capable of influencing the growth and function of heart cells in vitro. To better understand the role TGF-beta might play as a paracrine mediator of cardiac hypertrophy, the expression, secretion, and growth effects of TGF-beta were examined. Neonatal cardiac fibroblasts in vitro secreted latent TGF-beta 1 and TGF-beta 2 as high as 15 ng/10(6) cells. Angiotensin II (ANG II) and norepinephrine (NE) each augmented up to threefold the expression and secretion of latent TGF-beta 1 and TGF-beta 2 and also induced a shift in isoform predominance from beta 1 to beta 2. Each agent individually produced hypertrophic growth of neonatal cardiocytes and hyperplastic growth of cardiac fibroblasts. Paradoxically, the combination of NE and ANG II at intermediate and high concentrations resulted in less TGF-beta secretion (compared with either agent alone) and in hypertrophic growth of fibroblasts. These results suggest that the growth-promoting effects of ANG II and NE may in part be mediated via a paracrine stimulation of TGF-beta secretion.

Abstract 28: Formation of Podocyte-Derived Microparticles in Diabetic Glomerular Injury

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Dylan Burger ◽  
Jean-Francois Thibodeau ◽  
Chet Holterman ◽  
Kevin D Burns ◽  
Christopher R Kennedy
Keyword(s):  
Kidney Disease ◽  
Capillary Pressure ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cyclic Stretch ◽  
Nanoparticle Tracking Analysis ◽  
Ang Ii ◽  
Glomerular Injury

Hypertension is a significant cause of progressive kidney disease, particularly in the presence of diabetes. Under such conditions, increased glomerular capillary pressure subjects podocytes, specialized glomerular epithelial cells critical to filtration, to mechanical stress resulting in podocyte injury/dysfunction. Microparticles (MPs) are small (0.1-1.0 μm), membranous vesicles shed from the cell surface following injury. However, whether podocyte MP formation reflects glomerular injury is unknown. We examined MP formation by podocytes in vitro and in vivo. Conditionally immortalized human podocytes were exposed to 10% equibiaxial cyclic stretch (a mimic of increased intraglomerular pressure), high glucose (HG, 25 mM), mannitol (osmotic control), angiotensin II (Ang II, 500 nM) or transforming growth factor beta (TGF-β, 5 ng/mL). Additionally, urinary podocyte MPs were quantified in two mouse models of diabetic kidney disease: streptozotocin (STZ) and OVE26. MPs were characterized by nanoparticle tracking analysis and quantified by Annexin V (total MPs) or podocalyxin (podocyte MPs) labeling and flow cytometry. Podocyte-derived vesicles were identifiable in both media and urine samples with a mean size of 236 nm by nanoparticle tracking analysis. In vitro, cyclic stretch was associated with a 3-fold increase in MP release after 24 hours (P<0.01, n=6). HG increased MP release 5-fold after 24 hours (P<0.05, n=6). Mannitol had no effect on MP formation by either normal or stretched podocytes and neither Ang II, nor TGF-β altered podocyte MP formation over 24 hours. In vivo, both models of diabetes displayed typical hallmarks of renal injury (proteinuria, mesangial expansion). In OVE26 mice urinary podocyte MPs were elevated compared with their wild-type littermates (17479±8329 vs. 7 ±7, P<0.05, n=5-7). Similarly, STZ-treated mice displayed increased urinary podocyte MPs as compared with untreated (18035±3813 vs. 43±34, P<0.001, n=9-18) and urinary MPs levels were positively correlated with albuminuria (r2=0.74, P<0.01). Our results suggest that podocytes produce MPs which are released into urine and are indicative of glomerular injury. Such processes may be mediated by intraglomerular capillary pressure and hyperglycemia.

Differential response of cardiac fibroblasts from young adult and senescent rats to ANG II

2003 ◽  
Vol 284 (4) ◽  
pp. H1454-H1459 ◽  
Author(s):  
K. Shivakumar ◽  
David E. Dostal ◽  
Kenneth Boheler ◽  
Kenneth M. Baker ◽  
Edward G. Lakatta
Keyword(s):  
Young Adult ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Receptor Subtype ◽  
Mrna Levels ◽  
Ang Ii ◽  
Adult Rats ◽  
Collagen Production ◽  
Age Related

The intracardiac ANG II-forming pathway is activated in the senescent myocardium, raising the possibility of enhanced ANG II effects on cardiac fibroblasts. This study established an in vitro model of cultured cardiac fibroblasts from aged rats to examine if the response of these cells to ANG II is modified in the aged heart. Levels of mRNA encoding renin, angiotensinogen, and the AT1 receptor subtype in cardiac fibroblasts from young adult and senescent rats were quantified by RT-PCR, net collagen production by a hydroxyproline-based assay, and transforming growth factor (TGF)-β levels using a commercial kit. In cardiac fibroblasts from young adult rats, ANG II significantly enhanced AT1mRNA levels, net collagen production, and TGF-β production. In fibroblasts from the aged myocardium, ANG II downregulated AT1 mRNA expression, had a less pronounced effect on net collagen production, and had no effect on TGF-β production. Such age-related modification of the response of cardiac fibroblasts to ANG II may counteract the effects of augmented intracardiac ANG II production in the senescent heart, limiting fibrogenesis.

scholarly journals Ghrelin Ameliorates Angiotensin II-Induced Myocardial Fibrosis by Upregulating Peroxisome Proliferator-Activated Receptor Gamma in Young Male Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Qian Wang ◽  
Xin Sui ◽  
Rui Chen ◽  
Pei-Yong Ma ◽  
Yong-Liang Teng ◽  
...  
Keyword(s):  
Myocardial Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Male Rats ◽  
Peroxisome Proliferator ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Collagen Iii

Angiotensin (Ang) II contributes to the formation and development of myocardial fibrosis. Ghrelin, a gut peptide, has demonstrated beneficial effects against cardiovascular disease. In the present study, we explored the effect and related mechanism of Ghrelin on myocardial fibrosis in Ang II-infused rats. Adult Sprague-Dawley (SD) rats were divided into 6 groups: Control, Ang II (200ng/kg/min, microinfusion), Ang II+Ghrelin (100μg/kg, subcutaneously twice daily), Ang II+Ghrelin+GW9662 (a specific PPAR-γinhibitor, 1 mg/kg/d, orally), Ang II+GW9662, and Ghrelin for 4 wks. In vitro, adult rat cardiac fibroblasts (CFs) were pretreated with or without Ghrelin, Ghrelin+GW9662, or anti-Transforming growth factor (TGF)-β1 antibody and then stimulated with or without Ang II (100 nmol/L) for 24 h. Ang II infusion significantly increased myocardial fibrosis, expression of collagen I, collagen III, and TGF-β1, as well as TGF-β1 downstream proteins p-Smad2, p-Smad3, TRAF6, and p-TAK1 (all p<0.05). Ghrelin attenuated these effects. Similar results were seen in Ang II-stimulated rat cardiac fibroblasts in vitro. In addition, Ghrelin upregulated PPAR-γexpressionin vivoandin vitro, and treatment with GW9662 counteracted the effects of Ghrelin. In conclusion, Ghrelin ameliorated Ang II-induced myocardial fibrosis by upregulating PPAR-γand in turn inhibiting TGF-β1signaling.

scholarly journals Pentosan polysulfate treatment preserves renal autoregulation in ANG II-infused hypertensive rats via normalization of P2X1 receptor activation

2010 ◽  
Vol 298 (5) ◽  
pp. F1276-F1284 ◽  
Author(s):  
Zhengrong Guan ◽  
Barry S. Fuller ◽  
Tatsuo Yamamoto ◽  
Anthony K. Cook ◽  
Jennifer S. Pollock ◽  
...  
Keyword(s):  
Renal Injury ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Receptor Activation ◽  
Inflammatory Factors ◽  
Ang Ii ◽  
Pentosan Polysulfate ◽  
Hypertensive Rats ◽  
Afferent Arterioles

Inflammatory factors are elevated in animal and human subjects with hypertension and renal injury. We hypothesized that inflammation contributes to hypertension-induced renal injury by impairing autoregulation and microvascular reactivity to P2X1 receptor activation. Studies were conducted in vitro using the blood-perfused juxtamedullary nephron preparation. Rats receiving ANG II (60 ng/min) infusion were treated with the anti-inflammatory agent pentosan polysulfate (PPS) for 14 days. The magnitude and progression of hypertension were similar in ANG II and ANG II+PPS-treated rats (169 ± 5 vs. 172 ± 2 mmHg). Afferent arterioles from control rats exhibited normal autoregulatory behavior with diameter decreasing from 18.4 ± 1.6 to 11.4 ± 1.7 μm when perfusion pressure was increased from 70 to 160 mmHg. In contrast, pressure-mediated vasoconstriction was markedly attenuated in ANG II-treated rats, and diameter remained essentially unchanged over the range of perfusion pressures. However, ANG II-treated rats receiving PPS exhibited normal autoregulatory behavior compared with ANG II alone rats. Arteriolar reactivity to ATP and β,γ-methylene ATP was significantly reduced in ANG II hypertensive rats compared with controls. Interestingly, PPS treatment preserved normal reactivity to P2 and P2X1 receptor agonists despite the persistent hypertension. The maximal vasoconstriction was 79 ± 3 and 81 ± 2% of the control diameter for ATP and β,γ-methylene ATP, respectively, similar to responses in control rats. PPS treatment significantly reduced α-smooth muscle actin staining in afferent arterioles and plasma transforming growth factor-β1 concentration in ANG II-treated rats. In conclusion, PPS normalizes autoregulation without altering ANG II-induced hypertension, suggesting that inflammatory processes reduce P2X1 receptor reactivity and thereby impair autoregulatory behavior in ANG II hypertensive rats.

Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-β1-mediated renal fibrosis and dysfunction

2008 ◽  
Vol 295 (5) ◽  
pp. E1234-E1242 ◽  
Author(s):  
Lin Tian ◽  
Cai Li ◽  
Jiping Qi ◽  
Peng Fu ◽  
Xiaoyan Yu ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Diabetic Rats ◽  
Retinol Binding Protein ◽  
Ang Ii ◽  
Urotensin Ii ◽  
Mechanism Study ◽  
Study Results ◽  
Tgf Β1

Urotensin II (UII) was identified as the ligand for a novel G protein-coupled receptor, GPR14. UII was found not only to have a potent vasoconstrictive action but also to have profibrotic effects in the heart. The present study was to define whether UII and GPR14 also play important roles in diabetes-induced renal fibrosis and dysfunction. Diabetic rats were induced using streptozotocin, and the rat proximal tubular epithelial cells (NRK-52E) were used for the in vitro mechanism study. Results showed that expression of UII and GPR14 was significantly upregulated at both mRNA and protein levels in the diabetic kidneys compared with controls. The upregulated expressions of UII and GPR14 in the kidney were accompanied by significant increases in the renal profibrotic factor transforming growth factor (TGF)-β1 expression, the renal extracellular matrix (fibronectin and collagen IV) accumulation, and the renal dysfunction (increases in urinal N-acetyl-β-d-glucosaminidase content, 24-h urinary retinol-binding protein excretion rate, and decrease in creatinine clearance rate). Exposure of NRK-52E cells to 10−8 mol/l UII for 48 h caused a significant increase of TGF-β1, but not ANG II, production that was GPR14- and calcium-dependent, since GPR14 small-interfering RNA and calcium channel blocker nimodipine or calcium chelator EDTA all could abolish the induction of TGF- β1 by UII. Furthermore, exposure of NRK-52E cells to TGF-β1 or ANG II also increased UII and GPR14 mRNA expressions. These results suggested that diabetes-induced upregulation of UII and GPR14, most likely through autocrine and/or paracrine mechanisms, plays an important role in TGF-β1-mediated renal fibrosis and dysfunction.

scholarly journals Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension

2008 ◽  
Vol 295 (2) ◽  
pp. F515-F524 ◽  
Author(s):  
Steven D. Crowley ◽  
Campbell W. Frey ◽  
Samantha K. Gould ◽  
Robert Griffiths ◽  
Phillip Ruiz ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Cardiac Hypertrophy ◽  
Transforming Growth Factor ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Transforming Growth Factor Β ◽  
Ang Ii ◽  
Lymphocyte Responses ◽  
Stimulation Of

Activation of the renin-angiotensin system contributes to the progression of chronic kidney disease. Based on the known cellular effects of ANG II to promote inflammation, we posited that stimulation of lymphocyte responses by ANG II might contribute to the pathogenesis of hypertensive kidney injury. We therefore examined the effects of the immunosuppressive agent mycophenolate mofetil (MMF) on the course of hypertension and kidney disease induced by chronic infusion of ANG II in 129/SvEv mice. Although it had no effect on the severity of hypertension or cardiac hypertrophy, treatment with MMF significantly reduced albuminuria and ameliorated kidney injury, decreasing glomerulosclerosis and reducing lymphocyte infiltration into the renal interstitium. Attenuation of renal pathology with MMF was associated with reduced expression of mRNAs for the proinflammatory cytokines interferon-γ and tumor necrosis factor-α and the profibrotic cytokine transforming growth factor-β. As infiltration of the kidney by T lymphocytes was a prominent feature of ANG II-dependent renal injury, we carried out experiments examining the effects of ANG II on lymphocytes in vitro. We find that exposure of splenic lymphocytes to ANG II causes prominent rearrangements of the actin cytoskeleton. These actions require the activity of Rho kinase. Thus, ANG II exaggerates hypertensive kidney injury by stimulating lymphocyte responses. These proinflammatory actions of ANG II seem to have a proclivity for inducing kidney injury while having negligible actions in the pathogenesis of cardiac hypertrophy.

Sialyltransferase7A promotes angiotensin II-induced cardiomyocyte hypertrophy via HIF-1α-TAK1 signalling pathway

2019 ◽  
Vol 116 (1) ◽  
pp. 114-126 ◽  
Author(s):  
Xiaoying Yan ◽  
Ran Zhao ◽  
Xiaorong Feng ◽  
Jingzhou Mu ◽  
Ying Li ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Transforming Growth Factor ◽  
Troponin T ◽  
Hypoxia Inducible Factor ◽  
Transforming Growth Factor Β ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Ang Ii

Abstract Aims Sialylation is up-regulated during the development of cardiac hypertrophy. Sialyltransferase7A (Siat7A) mRNA is consistently over-expressed in the hypertrophic left ventricle of hypertensive rats independently of genetic background. The aims of this study were: (i) to detect the Siat7A protein levels and its roles in the pathological cardiomyocyte hypertrophy; (ii) to elucidate the effect of sialylation mediated by Siat7A on the transforming-growth-factor-β-activated kinase (TAK1) expression and activity in cardiomyocyte hypertrophy; and (iii) to clarify hypoxia-inducible factor 1 (HIF-1) expression was regulated by Siat7A and transactivated TAK1 expression in cardiomyocyte hypertrophy. Methods and results Siat7A protein level was increased in hypertrophic cardiomyocytes of human and rats subjected to chronic infusion of angiotensin II (ANG II). Delivery of adeno-associated viral (AAV9) bearing shRNA against rat Siat7A into the left ventricular wall inhibited ventricular hypertrophy. Cardiac-specific Siat7A overexpression via intravenous injection of an AAV9 vector encoding Siat7A under the cardiac troponin T (cTNT) promoter aggravated cardiac hypertrophy in ANG II-treated rats. In vitro, Siat7A knockdown inhibited the induction of Sialyl-Tn (sTn) antigen and cardiomyocyte hypertrophy stimulated by ANG II. Mechanistically, ANG II induced the activation of TAK1-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling in parallel to up-regulation of Siat7A in hypertrophic cardiomyocytes. Siat7A knockdown inhibited activation of TAK1-NF-κB pathway. Interestingly, HIF-1α expression was increased in cardiomyocytes stimulated by ANG II but decreased after Siat7A knockdown. HIF-1α knockdown efficiently decreased TAK1 expression. ChIP and luciferase assays showed that HIF-1α transactivated the TAK1 promoter region (nt −1285 to −1274 bp) in the cardiomyocytes following ANG II stimulus. Conclusion Siat7A was up-regulated in hypertrophic myocardium and promoted cardiomyocyte hypertrophy via activation of the HIF-1α-TAK1-NF-κB pathway.

Fluorofenidone attenuates vascular remodeling in hypoxia-induced pulmonary hypertension of rats

2014 ◽  
Vol 92 (1) ◽  
pp. 58-69 ◽  
Author(s):  
Xian-Wei Li ◽  
Jie Du ◽  
Gao-Yun Hu ◽  
Chang-Ping Hu ◽  
Dai Li ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Remodeling ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Brdu Incorporation ◽  
Pulmonary Vascular Remodeling ◽  
Collagen Iii ◽  
Pulmonary Arterial

Fluorofenidone (AKF-PD) is a novel pyridone derivate that targets transforming growth factor-β1 (TGF-β1) signaling. Previous studies have proven that AKF-PD functions as an antifibrotic agent in pulmonary fibrosis and renal fibrosis models. Activated TGF-β1 signaling is thought to be a major feature of pulmonary hypertension (PH). TGF-β1 exerts powerful pro-proliferation effects on pulmonary arterial smooth muscle cells (PASMCs), and hence, prompts vascular remodeling. This study is designed to investigate the effect of AKF-PD on vascular remodeling in a rat model of hypoxia-induced PH. PH was induced in rats by 4 weeks of hypoxia. The expression of TGF-β1, collagen I, and collagen III was analyzed by ELISA, immunohistochemistry, real-time PCR, or Western blot. Proliferation of cultured PASMCs was determined by the BrdU incorporation method and flow cytometry. The results showed that AKF-PD treatment (0.5 or 1.0 g·(kg body mass)·d−1) for 4 weeks attenuated pulmonary vascular remodeling and improved homodynamic parameters. TGF-β1 level was significantly down-regulated by AKF-PD both in vivo and in vitro. Furthermore, hypoxia- and TGF-β1-induced PASMC proliferation and collagen expression were both significantly suppressed by AKF-PD. These results suggest that AKF-PD ameliorates the progression of PH induced by hypoxia in rats through its regulation of TGF-β1 expression, PASMC proliferation, and the extracellular matrix.

Atorvastatin attenuates angiotensin II-induced inflammatory actions in the liver

2009 ◽  
Vol 296 (2) ◽  
pp. G147-G156 ◽  
Author(s):  
Montserrat Moreno ◽  
Leandra N. Ramalho ◽  
Pau Sancho-Bru ◽  
Marta Ruiz-Ortega ◽  
Fernando Ramalho ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Transforming Growth Factor ◽  
Inflammatory Cells ◽  
Intercellular Adhesion Molecule ◽  
Ang Ii ◽  
Beneficial Effects ◽  
Tgf Β1

Statins exert beneficial effects in chronically damaged tissues. Angiotensin II (ANG II) participates in liver fibrogenesis by inducing oxidative stress, inflammation, and transforming growth factor-β1 (TGF-β1) expression. We investigate whether atorvastatin modulates ANG II-induced pathogenic effects in the liver. Male Wistar rats were infused with saline or ANG II (100 ng·kg−1·min−1) for 4 wk through a subcutaneous osmotic pump. Rats received either vehicle or atorvastatin (5 mg·kg−1·day−1) by gavage. ANG II infusion resulted in infiltration of inflammatory cells (CD43 immunostaining), oxidative stress (4-hydroxynonenal), hepatic stellate cells (HSC) activation (smooth muscle α-actin), increased intercellular adhesion molecule (ICAM-1), and interleukin-6 hepatic gene expression (quantitative PCR). These effects were markedly blunted in rats receiving atorvastatin. The beneficial effects of atorvastatin were confirmed in an additional model of acute liver injury (carbon tetrachloride administration). We next explored whether the beneficial effects of atorvastatin on ANG II-induced actions are also reproduced at the cellular level. We studied HSC, a cell type with inflammatory and fibrogenic properties. ANG II (10−8M) stimulated cell proliferation, proinflammatory actions (NF-κB activation, ICAM-1 expression, interleukin-8 secretion) as well as expression of procollagen-α1(I) and TGF-β1. All of these effects were reduced in the presence of atorvastatin (10−7M). These results indicate that atorvastatin attenuates the pathogenic events induced by ANG II in the liver both in vivo and in vitro. Therefore, statins could have beneficial effects in conditions characterized by hepatic inflammation.

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