Pharmacological blockage of ICAM-1 improves angiotensin II-induced cardiac remodeling by inhibiting adhesion of LFA-1+ monocytes

2019 ◽  
Vol 317 (6) ◽  
pp. H1301-H1311 ◽  
Author(s):  
Qiu-Yue Lin ◽  
Ping-Ping Lang ◽  
Yun-Long Zhang ◽  
Xiao-Lei Yang ◽  
Yun-Long Xia ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Adhesion Molecules ◽  
Vascular Endothelium ◽  
Cardiac Remodeling ◽  
Leukocyte Adhesion ◽  
Neutralizing Antibody ◽  
Ang Ii ◽  
Cardiac Contractile ◽  
And Migration

Intercellular adhesion molecule-1 (ICAM-1) is a member of an immunoglobulin-like superfamily of adhesion molecules that mediate leukocyte adhesion to vascular endothelium and are involved in several cardiovascular diseases, including ischemia-reperfusion injury, myocardial infarction, and atherosclerosis. However, the role of ICAM-1 in angiotensin II (ANG II)-induced cardiac remodeling in mice remains unclear. Wild-type mice were administered an IgG control or ICAM-1 neutralizing antibody (1 and 2 mg/mouse, respectively) and ANG II (1,000 ng·kg−1·min−1) for up to 14 days. Cardiac contractile function and structure were detected by echocardiography. Hypertrophy, fibrosis, and inflammation were assessed by histological examination. The infiltration of lymphocyte function-associated antigen-1 (LFA-1+) monocytes/macrophages was assessed by immunostaining. The mRNA expression of genes was evaluated by quantitative RT-PCR analysis. Protein levels were tested by immunoblotting. We found that ICAM-1 expression in ANG II-infused hearts and ICAM-1 levels in serum from human patients with heart failure were significantly increased. Moreover, ANG II infusion markedly enhanced ANG II-induced hypertension, caused cardiac contractile dysfunction, and promoted cardiac hypertrophy, fibrosis, and LFA-1+ macrophage infiltration. Conversely, blockage of ICAM-1 with a neutralizing antibody dose-dependently attenuated these effects. Moreover, our in vitro data further demonstrated that blocking ICAM-1 inhibited ANG II-induced LFA-1+ macrophage adhesion to endothelial cells and migration. In conclusion, these results provide novel evidence that blocking ICAM-1 exerts a protective effect in ANG II-induced cardiac remodeling at least in part through the modulation of adhesion and infiltration of LFA-1+ macrophages in the heart. Inhibition of ICAM-1 may represent a new therapeutic approach for hypertrophic heart diseases. NEW & NOTEWORTHY Leukocyte adhesion to vascular endothelium is a critical step in cardiovascular diseases. ICAM-1 is a member of immunoglobulin-like superfamily of adhesion molecules that binds LFA-1 to mediate leukocytes adhesion and migration. However, the significance of ICAM-1 in ANG II-induced cardiac remodeling remains unclear. This study reveals that blocking of ICAM-1 prevents ANG II-induced cardiac remodeling via modulating adhesion and migration of LFA-1+ monocytes, may serve as a novel therapeutic target for hypertensive cardiac diseases.

Abstract P363: Annexin-A1 Deficiency Exaggerates Cardiac Remodeling In Angiotensin II-induced Hypertension

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Kristy Jackson ◽  
Jaideep Singh ◽  
Yen Zhi Ng ◽  
Cheng Peng ◽  
Anida Velagic ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Cardiac Remodeling ◽  
Physiological Role ◽  
Preclinical Model ◽  
Annexin A1 ◽  
Ang Ii ◽  
Cardiac Damage ◽  
Induced Hypertension ◽  
Deficient Mice

Introduction: We have previously demonstrated that the naturally-occurring anti-inflammatory and pro-resolving protein Annexin-A1 (Anx-A1) limits the acute inflammatory response post myocardial infarction, but its impact on chronic inflammation, such as hypertension, has not been explored. This study aims to investigate the role of Anx-A1 in a preclinical model of hypertension, induced by angiotensin-II (Ang-II). Methods: 15-week-old male C57BL/6 or ANXA1 -/- were anesthetized (isoflurane, 2-4% v/v) and implanted with an osmotic minipump randomly assigned to receive Ang-II (0.7mg/kg/day) or vehicle (saline). Radiotelemetry recordings of blood pressure were taken at 10 intermittent timepoints from baseline to the end of the 29-day infusion period. Animals were euthanized with pentobarbitone (100mg/kg; i.p.) at endpoint and organ weights recorded and normalized to bodyweight. Left ventricle (LV) samples were stained with picrosirius red to assess total LV collagen deposition. Results: Ang II-induced mice at the end of the study had elevated mean arterial pressure (MAP), cardiac hypertrophy and fibrosis compared to normotensive mice (Table). Anx-A1 deficient mice given Ang II had an even greater increase in MAP and cardiac remodeling compared to WT. Interestingly, MAP of Anx-A1 deficient mice at baseline is significantly higher compare to C57BL/6 counterparts (Table). Conclusion: This is the first study to demonstrate that deficiency of Anx-A1 exaggerates cardiac remodeling in AngII-induced hypertension, suggesting that endogenous Anx-A1 might play previously unappreciated physiological role in regulating blood pressure. This supports the development of Anx-A1 based pharmacotherapy against hypertension-induced cardiac damage.

scholarly journals Dapagliflozin: a Sodium-glucose Cotransporter 2 Inhibitor, Attenuates Angiotensin II-induced Cardiac Fibrotic Remodeling by Regulating TGFβ1/ Smad Signaling

2021 ◽  
Author(s):  
Yuze Zhang ◽  
Xiaoyan Lin ◽  
Yong Chu ◽  
Xiaoming Chen ◽  
Heng Du ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Remodeling ◽  
Sglt2 Inhibitor ◽  
Left Ventricular ◽  
Ang Ii ◽  
Smad Signaling ◽  
Sd Rats ◽  
Sodium Glucose Cotransporter ◽  
Tgf Β1

Abstract Background:Cardiac remodeling is one of the major risk factors for heart failure. In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of the first hospitalization for heart failure, possibly through glucose-independent mechanisms, but the underlying mechanisms remain largely unknown. This study aimed to shed light on the efficacy of dapagliflozin in reducing cardiac remodeling and potential mechanisms.Methods:Sprague-Dawley (SD) rats, induced by chronic infusion of Angiotensin II (Ang II) at a dose of 520 ng/kg per minute for 4 weeks with ALZET® mini-osmotic pumps, were treated with either SGLT2 inhibitor dapagliflozin (DAPA) or vehicle alone. Echocardiography was performed to determine cardiac structure and function. Cardiac fibroblasts (CFs) were treated with Ang II with or without the indicated concentration of DAPA. The protein levels of collagen and TGF-β1/Smad signaling were measured along with body weight, and blood biochemical indexes.Results:DAPA treatment resulted in the amelioration of left ventricular dysfunction in Ang II-infused SD rats without affecting blood glucose and blood pressure. Myocardial hypertrophy, fibrosis and increased collagen synthesis caused by Ang II infusion were significantly inhibited by DAPA treatment. In vitro, DAPA inhibit the Ang II-induced collagen production of CFs. Immunoblot with heart tissue homogenates from chronic Ang II-infused rats revealed that DAPA inhibited the activation of TGF-β1/Smads signaling.Conclusion:DAPA ameliorates Ang II-induced cardiac remodeling by regulating the TGF-β1/Smad signaling in a glucose-independent manner. DAPA may serve as a novel therapy for pathological cardiac remodeling.

scholarly journals A GSK3-SRF Axis Mediates Angiotensin II Induced Endothelin Transcription in Vascular Endothelial Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuyu Yang ◽  
Huidi Wang ◽  
Hongwei Zhao ◽  
Xiulian Miao ◽  
Yan Guo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Serum Response Factor ◽  
Vascular Endothelial Cells ◽  
Glycogen Synthase ◽  
Vascular Endothelial ◽  
Ang Ii ◽  
Over Expression ◽  
H3 Acetylation

Endothelin, encoded by ET1, is a vasoactive substance primarily synthesized in vascular endothelial cells (VECs). Elevation of endothelin levels, due to transcriptional hyperactivation, has been observed in a host of cardiovascular diseases. We have previously shown that serum response factor (SRF) is a regulator of ET1 transcription in VECs. Here we report that angiotensin II (Ang II) induced ET1 transcription paralleled activation of glycogen synthase kinase 3 (GSK3) in cultured VECs. GSK3 knockdown or pharmaceutical inhibition attenuated Ang II induced endothelin expression. Of interest, the effect of GSK3 on endothelin transcription relied on the conserved SRF motif within the ET1 promoter. Further analysis revealed that GSK3 interacted with and phosphorylated SRF at serine 224. Phosphorylation of SRF by GSK3 did not influence its recruitment to the ET1 promoter. Instead, GSK3-mediated SRF phosphorylation potentiated its interaction with MRTF-A, a key co-factor for SRF, which helped recruit the chromatin remodeling protein BRG1 to the ET1 promoter resulting in augmented histone H3 acetylation/H3K4 trimethylation. Consistently, over-expression of a constitutively active GSK enhanced Ang II-induced ET1 transcription and knockdown of either MRTF-A or BRG1 abrogated the enhancement of ET1 transcription. In conclusion, our data highlight a previously unrecognized mechanism that contributes to the transcriptional regulation of endothelin. Targeting this GSK3-SRF axis may yield novel approaches in the intervention of cardiovascular diseases.

Abstract 513: Evaluation of Proinflammatory Effects of Low Dose Angiotensin II Infusion in Intact Female Mice and Adiponectin Deficient Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Esther Yu ◽  
Xia Wang ◽  
Jaya Pamidimukkala
Keyword(s):  
Angiotensin Ii ◽  
Mrna Expression ◽  
Adhesion Molecules ◽  
Endothelial Activation ◽  
Tissue Expression ◽  
Renal Tissue ◽  
Protective Effects ◽  
Ang Ii ◽  
Female Mice ◽  
Deficient Mice

Circulating vasoactive peptide Angiotensin II (ANGII) has a well-known role in the development of hypertension and other cardiovascular diseases. In addition it has significant proinflammatory actions in the vascular wall inducing the production of reactive oxygen species, inflammatory cytokines and adhesion molecules. It has been previously shown that estrogen in female mice protects against ANGII mediated hypertension and against proinflammatory effects. It is not clear if the protective effects of estrogen extend to adiponectin deficient mice. Adiponectin is one of the few peptides secreted by fat to have anti-inflammatory properties. The present study evaluates the effect of chronic ANGII infusion on expression of cytokines in female C57BL/6J and adiponectin deficient mice (adipo-/-). Female mice (24- 28wks), were implanted with osmotic pump containing either ANG II (800 ng/Kg /min) or saline. Blood samples and tissue were collected at the end of 14 days. Plasma levels of TNFalpha and IL6 were measured using enzyme linked immunoabsorbent assay. Renal tissue expression of the cytokines were quantified using real-time PCR (Eppendorf Realplex 4 mastercycler) and SYBR Green ROX mastermix. Plasma TNFα levels were similar in saline infused C57Bl/6J(11±1 pg/ml) and adiponectin deficient mice(10± 1 pg/ml). ANGII did not significantly increase TNFα in the control(14±3 pg/ml) or adipo-/- mice(13+1 pg/ml). Plasma IL6 levels were also not significantly different in the two groups. A microarray for mRNA expression of markers of endothelial activation and adhesion molecules was also performed in the renal tissue. Preliminary data show that TNFalpha mRNA expression levels were not increased by ANG II infusion and IL6 expression was undetectable. ANGII also did not alter E-Selectin,VCAM1, Collagen1a1 and eNOS expression. In conclusion, ANGII infusion did not result in a proinflammatory milieu in both female C57BL/6J and Adipo -/- mice.

Abstract 3467: Fibulin-2 Enhances Angiotensin-II-Induced Transforming Growth Factor (TGF)-β Activation in Promoting Cardiac Remodeling in the Mouse Model I n Vivo

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hangxiang Zhang ◽  
Hailong Dong ◽  
Jing Wu ◽  
Mon-Li Chu ◽  
Takeshi Tsuda
Keyword(s):  
Angiotensin Ii ◽  
Signaling Pathways ◽  
Cardiac Remodeling ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Ang Ii ◽  
Downstream Signaling ◽  
Collagen Iii

Background: Angiotensin-II (Ang-II) is a potent neurohormone responsible for progression of cardiac remodeling in which TGF-β serves as a principal downstream mediator. In our previous study, genetic deletion of fibulin-2 attenuated progression of ventricular dysfunction after experimental myocardial infarction (MI). Because Ang-II plays a central role in post-MI ventricular remodeling, we tested the hypothesis that fibulin-2 modulates Ang-II-induced cardiac remodeling. Methods: Subpressor dosage of Ang-II (0.2 μg/kg/min) was infused over 4 weeks by mini-osmotic-pump in age matched wild-type (WT), heterozygous, and fibulin-2 null (Fbln2 −/− ) adult male mice. Sham mice received normal saline. Results: There was no blood pressure change throughout Ang-II treatment. WT developed significant left ventricular (LV) hypertrophy by Ang-II, whereas Ang-II-treated Fbln2 −/− mice showed no noticeable hypertrophy compared with sham: LV/body weight ratio (WT 4.83±0.18 vs. Fbln2 −/− 4.01± 0.12 mg/g, p < 0.05) and LV posterior wall thickness by echocardiogram (WT 0.76± 0.03 vs. Fbln2 −/− 0.71± 0.02 mm, p < 0.05). Atrial natriuretic peptide (ANP) mRNA expression was significantly increased in Ang-II-treated WT compared with sham, but not in Ang-II-treated Flbn2 −/− . Ang-II also induced significant up-regulation in fibulin-2, Collagen I, Collagen III, and MMP-2 mRNA level in WT, but not in Fbln2 −/− . Both TGF-β1 mRNA and protein expression were significantly up-regulated in Ang-II-treated WT, but were unchanged in Ang-II-treated Fbln2 −/− compared with sham. Activation of TGF-β downstream signaling proteins, phosphorylated forms of Smad2, TGF-β-activated kinase 1 (TAK1), and p38MAPK, were all significantly increased in Ang-II-treated WT, as opposed to no increase in Ang-II-treated Fbln2 −/− compared with sham. Heterozygous mice showed intermediate increase in LV hypertrophy, matrix protein synthesis, and activation of TGF-β downstream signaling pathways between WT and Fbln2 −/− . Conclusions: Our data suggest that fibulin-2 enhances Ang-II-induced myocardial hypertrophy via up-regulation of TGF-β and its downstream signaling pathways in dose-dependent fashion and that fibulin-2 is required for Ang-II-induced TGF-β activation. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).

Angiotensin II-mediated oxidative stress and procollagen-1 expression in cardiac fibroblasts: blockade by pravastatin and pioglitazone

2006 ◽  
Vol 291 (4) ◽  
pp. H1738-H1745 ◽  
Author(s):  
Jiawei Chen ◽  
Jawahar L. Mehta
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Cardiac Remodeling ◽  
Cardiac Fibroblasts ◽  
Ang Ii ◽  
Mobility Shift ◽  
Positive Interaction ◽  
Mapk Activation ◽  
Variable Effect ◽  
Ppar Γ

Angiotensin II (ANG II), a product of renin-angiotensin system activation, enhances collagen synthesis, which is a key event in cardiac remodeling after myocardial infarction. Inhibition of cardiac remodeling is now a target of multiple therapies, including 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, and peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands. We examined the potential antifibrotic effect of the combination of a statin (pravastatin) and a PPAR-γ ligand (pioglitazone) in ANG II-treated mouse cardiac fibroblasts. ANG II treatment induced procollagen-1 expression, which was inhibited by pravastatin and pioglitazone in a dose-dependent fashion. Pretreatment of fibroblasts with low therapeutic concentrations of either pravastatin (0.1 μM) or pioglitazone (5 μM) only slightly decreased ANG II-induced NADPH oxidase expression, superoxide anion production, and procollagen-1 expression; however, the combination of pravastatin and pioglitazone markedly modulated these effects of ANG II. The combination also blocked ANG II-mediated p38 MAPK and p44/42 MAPK activation. Electrophoretic mobility shift assay showed that ANG II activated transcription factors NF-κB and activator protein-1 (AP-1). Although pravastatin and pioglitazone alone had a variable effect on NF-κB and AP-1 activation, their combination exerted a potent inhibitory effect on the activation of both NF-κB and AP-1. The effects of pravastatin and pioglitazone in combination on superoxide generation and procollagen-1 expression mimicked those of α-tocopherol and γ-tocopherol, two potent antioxidants. Thus it appears that there is a positive interaction between pravastatin and pioglitazone in modulating ANG II-mediated oxidative stress, inhibiting MAPK activation, and procollagen-1 expression.

A critical role for TNFα in the selective attachment of mononuclear leukocytes to angiotensin-II-stimulated arterioles

Blood ◽  
2007 ◽  
Vol 110 (6) ◽  
pp. 1895-1902 ◽  
Author(s):  
Teresa Mateo ◽  
Yafa Naim Abu Nabah ◽  
Mercedes Losada ◽  
Rossana Estellés ◽  
Chantal Company ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mononuclear Cell ◽  
Mononuclear Cells ◽  
Leukocyte Adhesion ◽  
Critical Role ◽  
Mononuclear Leukocytes ◽  
Ang Ii ◽  
Neutrophil Accumulation ◽  
Mononuclear Leukocyte ◽  
Necrosis Factor Alpha

Abstract Angiotensin II (Ang-II) exerts inflammatory activity and is involved in different cardiovascular disorders. This study has evaluated the involvement of tumor necrosis factor alpha (TNFα) in the leukocyte accumulation elicited by Ang-II. Ang-II (1 nM intraperitoneally in rats) induced TNFα release at 1 hour followed by neutrophil and mononuclear cell recruitment. The administration of an antirat TNFα antiserum had no effect on Ang-IIinduced neutrophil accumulation but inhibited the infiltration of mononuclear cells and reduced CC chemokine content in the peritoneal exudate. Pretreatment with either an anti-TNFα or an anti-IL-4 antiserum decreased Ang-II-induced arteriolar mononuclear leukocyte adhesion by 68% and 60%, respectively, in the rat mesenteric microcirculation. While no expression of TNFα was found in the postcapillary venules of Ang-II-injected animals, this cytokine was clearly up-regulated in the arterioles. Stimulation of human umbilical arterial endothelial cells (HUAECs) or isolated human mononuclear cells with 1 μM Ang-II caused increased TNFα mRNA expression and protein. Neutralization of TNFα activity reduced Ang-II-induced MCP-1, MCP-3, and RANTES release from HUAECs and MIP-1α from blood cells. In conclusion, the selective mononuclear leukocyte adhesion to Ang-II-stimulated arterioles is largely mediated by TNFα in cooperation with constitutive IL-4. Therefore, neutralization of TNFα activity may help to prevent mononuclear cell infiltration and the progression of the atherogenic process.

scholarly journals 3,4-Di-O-Caffeoylquinic Acid Inhibits Angiotensin-II-Induced Vascular Smooth Muscle Cell Proliferation and Migration by Downregulating the JNK and PI3K/Akt Signaling Pathways

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Wen-Fei Chiou ◽  
Chien-Chih Chen ◽  
Bai-Luh Wei
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Ang Ii ◽  
Caffeoylquinic Acid ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

We previously reported 3,4-di-O-caffeoylquinic acid (CQC) protected vascular endothelial cells against oxidative stress and restored impaired endothelium-dependent vasodilatation. Here, we further investigated its anti-atherosclerotic effect against angiotensin II (Ang II) evoked proliferation and migration of cultured rat vascular smooth muscle cells (rVSMC). The results showed CQC (1–20μM) clearly inhibited Ang-II-stimulated BrdU incorporation and cell migration of rVSMC in a concentration-dependent manner but without significant cytotoxicity. Western blot analysis revealed Ang II increased the phosphorylation levels of Akt and mitogen-activated protein kinases (MAPKs;p38, ERK1/2 and JNK) in rVSMC. In the presence of phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin and three individual MAPK inhibitors SB203580, PD98059 and SP600125, both Ang-II-induced cell proliferation and migration were significantly attenuated, although to differing extents, suggesting the PI3K and MAPK signal pathways all participated in regulating rVSMC proliferation and migration. Also, the CQC pretreatment markedly suppressed Ang-II-induced phosphorylation of Akt and JNK rather than ERK1/2, although it failed to affect p38 phosphorylation. In conclusion, our data demonstrate CQC may act by down-regulating Akt, JNK and part of the ERK1/2 pathways to inhibit Ang-II-induced rVSMC proliferation and migration. The anti-atherosclerotic effect of CQC is achieved either by endothelial cells protection or by VSMC proliferation/migration inhibition, suggesting this compound may be useful in preventing vascular diseases.

Role of cyclic AMP response element binding protein (CREB) in angiotensin II-induced responses in vascular smooth muscle cells

2020 ◽  
Author(s):  
Vanessa Truong ◽  
Madhu B Anand-Srivastava ◽  
Ashok K Srivastava
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ang Ii ◽  
Response Element ◽  
And Migration

Cyclic adenosine monophosphate response element (CRE) binding protein (CREB) is a nuclear transcription factor that regulates the transcription of several genes containing the CRE sites in their promoters. CREB is activated by phosphorylation on a key serine residue, Ser 311, in response to a wide variety of extracellular stimuli including angiotensin II (Ang II). Ang II is an important vasoactive peptide and mitogen for vascular smooth muscle cells (VSMC) that in addition to regulating the contractile response in VSMC also plays an important role in phenotypic switch of vascular smooth muscle cells (VSMC) from contractile to a synthetic state. The synthetic VSMC are known to exhibit proliferative and migratory properties due to hyperactivation of Ang II-induced signaling events. Ang II has been shown to induce CREB phosphorylation/activation and transcription of genes implicated in proliferation, growth and migration. Here, we have highlighted some key studies that have demonstrated an important role of CREB in Ang II-mediated gene transcription, proliferation, hypertrophy and migration of VSMC.

scholarly journals Luteolin Inhibits Angiotensin II-Stimulated VSMC Proliferation and Migration through Downregulation of Akt Phosphorylation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Tongda Xu ◽  
Hong Zhu ◽  
Dongye Li ◽  
Yasong Lang ◽  
Lijuan Cao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Inhibitory Effect ◽  
Nuclear Antigen ◽  
Ang Ii ◽  
Proliferative Cell Nuclear Antigen ◽  
Vsmc Proliferation ◽  
Akt Phosphorylation ◽  
And Migration ◽  
Proliferation And Migration

Luteolin is a naturally occurring flavonoid found in many plants that possesses cardioprotective properties. The purpose of this study was to elucidate the effect of luteolin on vascular smooth muscle cells (VSMCs) proliferation and migration induced by Angiotensin II (Ang II) and to investigate the mechanism(s) of action of this compound. Rat VSMCs were culturedin vitro, and the proliferation and migration of these cells following Ang II stimulation were monitored. Different doses of luteolin were added to VSMC cultures, and the proliferation and migration rate were observed by MTT and Transwell chamber assays, respectively. In addition, the expressions of p-Akt (308), p-Akt (473), and proliferative cell nuclear antigen (PCNA) in VSMCs were monitored by Western blotting. This study demonstrated that luteolin has an inhibitory effect on Ang II-induced VSMC proliferation and migration. Further, the levels of p-Akt (308), p-Akt (473), and PCNA were reduced in VSMCs treated with both Ang II and luteolin compared to VSMCs treated with only Ang II. These findings strongly suggest that luteolin inhibits Ang II-stimulated proliferation and migration of VSMCs, which is partially due to downregulation of the Akt signaling pathway.

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