scholarly journals CYP2J2-Derived EETs Attenuated Angiotensin II-Induced Adventitial Remodeling via Reduced Inflammatory Response

2016 ◽  
Vol 39 (2) ◽  
pp. 721-739 ◽  
Author(s):  
Chi Zhou ◽  
Jin Huang ◽  
Junxiong Chen ◽  
Jinsheng Lai ◽  
Fasheng Zhu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Gene Delivery ◽  
Signaling Pathways ◽  
Nuclear Translocation ◽  
Wall Thickening ◽  
Protective Effects ◽  
Ang Ii ◽  
Independent Manner ◽  
Stat3 Phosphorylation ◽  
Arachidonic Acids

Background: Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acids (AA) to form epoxyeicosatrienoic acids (EETs), which exert beneficial roles in the treatment of cardiovascular diseases, but little is known about its role on adventitial remodeling. Methods: We used C57BL/6J mice in vivo and primary rat adventitial fibroblasts (AFs) in vitro treated with Angiotensin II to investigate the effects of CYP2J2 gene delivery and exogenous EETs administration on adventitial remodeling. Results: CYP/sEH system was found to exist in human adventitia, and involved in adventitial remodeling process. Exogenous EETs administration significantly inhibited Ang II-induced AFs activation, characterized by differentiation, proliferation, migration, and collagen synthesis. These protective effects were partially reversed by PPARγ antagonist GW9662 pretreatment or SOCS3 siRNA transfection. EETs suppressed Ang II-induced IκBα phosphorylation, subsequent NF-κB nuclear translocation via PPARγ dependent signaling pathway in AFs. Additionally, EETs reduced Ang II-induced JAK2, STAT3 phosphorylation and subsequent phosphor-STAT3 nuclear translocation, which were mediated by SOCS3 induction but independent of PPARγ activation. Furthermore, rAAV-CYP2J2 gene delivery reduced vessel wall thickening, AFs differentiation, proliferation and collagen deposition in aortic adventitia induced by Ang II infusion, which were mediated by NF-κB and SOCS3/JAK/STAT signaling pathways in blood pressure dependent and independent manner, respectively. Conclusion: We concluded that CYP2J2 overexpression attenuated Ang II-induced adventitial remodeling via PPARγ-dependent NF-κB and PPARγ-independent SOCS3/JAK/STAT inflammatory signaling pathways.

scholarly journals Alpha-Asarone Protects Endothelial Cells from Injury by Angiotensin II

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hai-Xia Shi ◽  
Jiajun Yang ◽  
Tao Yang ◽  
Yong-Liang Xue ◽  
Jun Liu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Cell Injury ◽  
Fluorescent Dyes ◽  
Umbilical Vein ◽  
Protective Effects ◽  
Ang Ii ◽  
Versus Model

α-Asarone is the major therapeutical constituent ofAcorus tatarinowiiSchott. In this study, the potential protective effects ofα-asarone against endothelial cell injury induced by angiotensin II were investigatedin vitro. The EA.hy926 cell line derived from human umbilical vein endothelial cells was pretreated withα-asarone (10, 50, 100 µmol/L) for 1 h, followed by coincubation with Ang II (0.1 µmol/L) for 24 h. Intracellular nitric oxide (NO) and reactive oxygen species (ROS) were detected by fluorescent dyes, and phosphorylation of endothelial nitric oxide synthase (eNOS) atSer1177was determined by Western blotting.α-Asarone dose-dependently mitigated the Ang II-induced intracellular NO reduction (P<0.01versus model) and ROS production (P<0.01versus model). Furthermore, eNOS phosphorylation (Ser1177) by acetylcholine was significantly inhibited by Ang II, while pretreatment for 1 h withα-asarone partially prevented this effect (P<0.05versus model). Additionally, cell viability determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay (105~114.5% versus control,P>0.05) was not affected after 24 h of incubation withα-asarone at 1–100 µmol/L. Therefore,α-asarone protects against Ang II-mediated damage of endothelial cells and may be developed to prevent injury to cardiovascular tissues.

Hexarelin protects rat cardiomyocytes from angiotensin II-induced apoptosis in vitro

2004 ◽  
Vol 286 (3) ◽  
pp. H1063-H1069 ◽  
Author(s):  
Jin-Jiang Pang ◽  
Rong-Kun Xu ◽  
Xiang-Bin Xu ◽  
Ji-Min Cao ◽  
Chao Ni ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Caspase 3 ◽  
Cardiomyocyte Apoptosis ◽  
Protective Effects ◽  
Ang Ii ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Rat Cardiomyocytes ◽  
Induced Apoptosis

Loss of cardiomyocytes by apoptosis is proposed to cause heart failure. Angiotensin II (ANG II), an important neurohormonal factor during heart failure, can induce cardiomyocyte apoptosis. Inasmuch as hexarelin has been reported to have protective effects in this process, we examined whether hexarelin can prevent cardiomyocytes from ANG II-induced cell death. Cultured cardiomyocytes from neonatal rats were stimulated with ANG II. Apoptosis was evaluated using fluorescence microscopy, TdT-mediated dUTP nick-end labeling (TUNEL) method, flow cytometry, DNA laddering, and analysis of cell viability by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). It was found that incubation with 0.1 μmol/l ANG II for 48 h increased cardiomyocyte apoptosis. Administration of 0.1 μmol/l hexarelin significantly decreased this ANG II-induced apoptosis and DNA fragmentation and increased myocyte viability. To further investigate the underlying mechanisms, caspase-3 activity assay and mRNA expression of Bax, Bcl-2, and growth hormone secretagogue receptor (GHS-R; the supposed hexarelin binding site) were examined. GHS-R mRNA was abundantly expressed in cardiomyocytes and was upregulated after administration of hexarelin. These results suggest that hexarelin abates cardiomyocytes from ANG II-induced apoptosis possibly via inhibiting the increased caspase-3 activity and Bax expression induced by ANG II and by increasing the expression of Bcl-2, which is depressed by ANG II. Whether the upregulated expression of GHS-R induced by hexarelin is associated with this antiapoptotic effect deserves further investigation.

β-Pro7Ang III is a novel highly selective angiotensin II type 2 receptor (AT2R) agonist, which acts as a vasodepressor agent via the AT2R in conscious spontaneously hypertensive rats

2015 ◽  
Vol 129 (6) ◽  
pp. 505-513 ◽  
Author(s):  
Mark Del Borgo ◽  
Yan Wang ◽  
Sanja Bosnyak ◽  
Morimer Khan ◽  
Pia Walters ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Angiotensin Ii ◽  
Protein Binding ◽  
Binding Site ◽  
Spontaneously Hypertensive Rats ◽  
Protective Effects ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

We have synthesized a highly selective compound that is able to target a protein-binding site [called angiotensin (Ang) II type 2 receptor, AT2R] in the cardiovascular system. This research tool will enhance our ability to stimulate AT2R to produce protective effects against cardiovascular disease.

Abstract 189: Natriuretic Peptide Receptor-A Regulates Angiotensin-II Mediated NF-κB Via Mkp-1 Dependent Pathway

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Gopi Venkatachalam ◽  
Umadevi Subramanian ◽  
Parthasarathy Arumugam ◽  
Elangovan Vellaichamy
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Nuclear Translocation ◽  
Heart Tissue ◽  
Male Rats ◽  
Natriuretic Peptide Receptor ◽  
Ang Ii ◽  
Hypertrophic Growth ◽  
Peptide Receptor

Atrial natriuretic peptide (ANP) exerts local anti-hypertrophic activity in heart tissue by binding to natriuretic peptide receptor (NPR)-A. However, patients with cardiac hypertrophy and congestive heart failure have elevated plasma and tissue levels of ANP and brain natriuretic peptide (BNP) along with Angiotensin II (Ang II). However, the rationale behind the impaired action of ANP in diseased state is not well understood. In this study, we sought to examine the signaling mechanism by which Ang II modulates local anti-hypertrophic effect through inhibition of Npr1 gene, which codes for NPR-A, in the heart. Hence, in vivo , Wistar male rats (n=8/group) were administered suppressor dose of Ang II (50ng/kg/min) for 14 days through implanted mini-osmotic pumps. Also, in vitro , H9C2 (2-1) cardio myofibroblast cells were exposed to Ang II (10 -7 M) for 20 hours. Upon treatment with Ang II, the mRNA and protein expression of Npr1 (p<0.01) was decreased with significant increase in expression of AT1R (p<0.01) in the heart tissues. In addition, a concomitant decrease in cGMP activity and production in isolated heart tissue membrane preparation was found in Ang II infused rats. Moreover, Ang II infusion causes a suppression of MKP-1 phosphatase; while enhancing the phosphorylation of ERK1/2 (p<0.01) and NF-κB (p<0.01) proteins. Similarly, H9C2 cells exhibited the hypertrophic growth with increased expression of AT1R and activation of ERK1/2 proteins on stimulation with Ang II. Furthermore, gene silencing using siRNA-NPR-A prior to Ang II treatment augmented the translocation of NF-κB and activation of ERK1/2 (3-fold). Whereas, pre-treatment with losartan or cGMP analog 8-Br-cGMP, an activator of cGMP-dependent protein kinases, abolished the stimulatory effects of Ang II on AT1R, NF-κB nuclear translocation and phosphorylation of MAPK, but activated the MKP-1 phosphatase. These results suggest that NPRA-cGMP signaling exerts inhibitory effects on Ang II by antagonizing the upstream signaling pathways and by activation of MKP-1 to counter-regulate NF-κB and MAPKs through cGMP dependent mechanism; thereby mediate local anti-hypertrophic activity in cardiac hypertrophy.

Abstract 095: Human (Pro)renin Receptor Activation Induces an Angiotensin II-Independent Pressor Response Mediated by NADPH Oxidase 4 Activity

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Michelle N Sullivan ◽  
Wencheng Li ◽  
Curt D Sigmund ◽  
Yumei Feng
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Signaling Pathways ◽  
Pressor Response ◽  
Receptor Activation ◽  
Fold Change ◽  
Mrna Levels ◽  
Ang Ii ◽  
Proteolytic Activation ◽  
Nadph Oxidase 4

The binding of prorenin to the (pro)renin receptor (PRR) induces non-proteolytic activation of prorenin and generation of angiotensin II (Ang II). PRR activation can also induce Ang II-independent signaling pathways. However, whether Ang II-independent signaling pathways are critical for blood pressure (BP) regulation is not known. To address this question, we created transgenic mice that overexpress the human PRR (hPRR) selectively in neurons (Syn-hPRR). Activated human prorenin (hPRO) cannot cleave endogenous mouse angiotensinogen to generate Ang II. Therefore, administration of hPRO to Syn-hPRR mice can be used to examine Ang II-independent PRR signaling in BP regulation. Intracerebroventricular (ICV) infusion of hPRO increases BP in Syn-hPRR mice (ΔMAP 23 ± 4.6, n = 4) but has no effect on wildtype (WT) mice (ΔMAP 2 ± 0.8, n = 6). The hPRO-induced pressor response in Syn-hPRR mice is unaffected by co-infusion with the Ang II type 1 receptor blocker losartan (ΔMAP 19 ± 5.2, n = 8), suggesting that the response is independent of Ang II. Interestingly, co-infusion with an inhibitor of the reactive oxygen species-generating enzyme NADPH oxidase (NOX), diphenyleneiodonium, nearly abolishes the hPRO-induced pressor response in Syn-hPRR mice (ΔMAP 4.7 ± 1.0, n = 4), indicating that NOX activity is required. Additionally, we find that basal NOX activity is enhanced in the Syn-hPRR hypothalamus relative to WT mice (1.4 fold change). We next examined which NOX isoform is responsible for the hPRO-induced pressor response and enhanced activity. NOX4 mRNA levels are greater (2.7 ± 0.6 fold change), but NOX1 (1.2 ± 0.3 fold change) and NOX2 (1.2 ± 0.3 fold change) mRNA levels are not different, in the hypothalamus of Syn-hPRR compared to WT mice (n = 3). Adenovirus-mediated delivery of NOX2, NOX4, or a scrambled sequence shRNA was ICV injected in Syn-hPRR mice. After 7 days, we found that treatment with NOX2 (ΔMAP 20 ± 5.2) or scrambled (ΔMAP 23 ± 3.2) shRNA had no effect on the hPRO-induced pressor response (n = 5). However, the hPRO-induced increase in BP is attenuated in Syn-hPRR mice injected with NOX4 shRNA (ΔMAP 5.9 ± 2.8). Together, these data indicate that NOX4 mediates the Ang II-independent pressor response to activation of the human (pro)renin receptor in Syn-hPRR mice.

scholarly journals Telmisartan improves myocardial remodeling by inhibiting leptin autocrine activity and activating PPARγ

2020 ◽  
Vol 245 (7) ◽  
pp. 654-666
Author(s):  
Hui Chen ◽  
Min Li ◽  
Lei Liu ◽  
Danjun Zhu ◽  
Gang Tian
Keyword(s):  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Cardiac Fibroblasts ◽  
Left Ventricular ◽  
Collagen Metabolism ◽  
Myocardial Remodeling ◽  
Ang Ii ◽  
Metabolism Disorder ◽  
Ppar Γ ◽  
Stat3 Phosphorylation

The mechanism responsible for myocardial remodeling in hypertensive left ventricular hypertrophy (LVH) is complex. This study was designed to investigate the role of telmisartan in improving myocardial remodeling in hypertensive LVH and to explore the molecular mechanisms underlying the effects of telmisartan on hypertensive LVH. Hypertensive LVH was established in eight-week-old male Sprague–Dawley (SD) rats by abdominal aortic constriction. Telmisartan was intragastrically administered six weeks after surgery. Telmisartan improved cardiac dysfunction and myocardial fibrosis and reduced myocardial renin-angiotensin-aldosterone system (RAAS) activity and leptin levels in hypertensive LVH rats. To assess the mechanism underlying hypertensive LVH, cardiac fibroblasts were treated in vitro with angiotensin II (Ang II) or leptin, plus various inhibitors. Ang II stimulated leptin synthesis and secretion in cardiac fibroblasts by promoting AP-1 nuclear translocation via the AT1R-ROS-ERK1/2 pathway. Leptin induced collagen metabolism disorder in cardiac fibroblasts via the JAK2/STAT3 pathway. Telmisartan improved collagen metabolism disorder by inhibiting leptin induced by local Ang II in an autocrine manner. Telmisartan also improved Ang II-induced collagen metabolism disorder by inhibiting STAT3 phosphorylation, a leptin downstream signal, by activating PPAR-γ. Telmisartan therefore improved myocardial remodeling in hypertensive LVH rats by acting as an AT1R antagonist, inhibiting leptin autocrine activity induced by local Ang II and by acting as a PPAR-γ agonist, inhibiting downstream leptin activation of STAT3 phosphorylation. These findings indicate the crosstalk between local myocardial RAAS and leptin and suggest a molecular mechanism by which telmisartan improves myocardial remodeling in hypertensive LVH. Impact statement This study shows the crosstalk between local myocardial RAAS and leptin in hypertensive LVH rats; that Ang II induces myocardial remodeling by stimulating leptin autocrine activity by promoting AP-1 nuclear translocation via the AT1R-ROS-ERK1/2 pathway; and that telmisartan improves myocardial remodeling by inhibiting local Ang II-induced leptin autocrine activity and by inhibiting the leptin downstream signal STAT3 phosphorylation by activating PPAR-γ. These findings reveal novel molecular mechanisms by which telmisartan improves myocardial remodeling and could help to identify therapeutic targets for hypertensive LVH.

scholarly journals Antagonizing Effects of Clematis apiifolia DC. Extract against Benzo[a]pyrene-Induced Damage to Human Keratinocytes

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Seung Eun Lee ◽  
See-Hyoung Park ◽  
Ju Ah Yoo ◽  
Kitae Kwon ◽  
Ji Woong Kim ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Human Keratinocytes ◽  
Antioxidant Response ◽  
Luciferase Reporter ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Cytochrome P450 1A1 ◽  
Independent Manner ◽  
Reporter Activity ◽  
Aryl Hydrocarbon

Background. Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon present in the atmosphere, has cytotoxic and carcinogenic effects. There have been no reports to demonstrate involvement of Clematis apiifolia DC. extract (CAE) in B[a]P-induced effects. This study was conducted to investigate the effect of CAE on B[a]P-induced effects and to elucidate its mechanism of action in HaCaT human keratinocytes. CAE inhibited aryl hydrocarbon receptor (AhR) signaling by decreasing both XRE reporter activity and expression of cytochrome P450 1A1 (CYP1A1) induced by B[a]P treatment in HaCaT cells. We also found that B[a]P-induced nuclear translocation of AhR and production of reactive oxygen species (ROS) and proinflammatory cytokines were attenuated by CAE treatment. CAE treatment suppressed B[a]P-induced phosphorylation of Src (Tyr416). In addition, dasatinib, a Src inhibitor, also inhibited B[a]P-induced nuclear translocation of AhR, similar to CAE treatment. In addition, CAE activated antioxidant response element (ARE) signaling by increasing ARE luciferase reporter activity and expression of ARE-dependent genes such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase [quinone] 1 (NQO1), and heme oxygenase-1 (HO-1). Nuclear translocation of Nrf2 by CAE was demonstrated by Western blot analysis and immunocytochemistry. The effects of CAE on ARE signaling were attenuated by knockdown of the Nrf2 gene. Inhibition of AhR signaling and activation of antioxidant activity by CAE operated in a reciprocally independent manner as evidenced by AhR and Nrf2 siRNA experiments. These findings indicate that CAE exerts protective effects against B[a]P by inhibiting AhR signaling and activating Nrf2-mediated signaling, suggesting its potential in protection from harmful B[a]P-containing pollutants.

Molecular mechanism of ADP-ribosyl cyclase activation in angiotensin II signaling in murine mesangial cells

2008 ◽  
Vol 294 (4) ◽  
pp. F982-F989 ◽  
Author(s):  
Seon-Young Kim ◽  
Rukhsana Gul ◽  
So-Young Rah ◽  
Suhn Hee Kim ◽  
Sung Kwang Park ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Tyrosine Kinase ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
Dependent Manner ◽  
Ang Ii ◽  
Akt Phosphorylation ◽  
Cyclase Activation ◽  
Adp Ribosyl Cyclase ◽  
Phosphoinositide 3 Kinase

ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca2+-mobilizing second messenger cyclic ADP-ribose (cADPR) from NAD+. In this study, we investigated the molecular basis of ADPR-cyclase activation and the following cellular events in angiotensin II (ANG II) signaling in mouse mesangial cells (MMCs). Treatment of MMCs with ANG II induced an increase in intracellular Ca2+ concentrations through a transient Ca2+ release via an inositol 1,4,5-trisphosphate receptor and a sustained Ca2+ influx via L-type Ca2+ channels. The sustained Ca2+ signal, but not the transient Ca2+ signal, was blocked by a cADPR antagonistic analog, 8-bromo-cADPR (8-Br-cADPR), and an ADPR-cyclase inhibitor, 4,4′-dihydroxyazobenzene (DHAB). In support of the results, ANG II stimulated cADPR production in a time-dependent manner, and DHAB inhibited ANG II-induced cADPR production. Application of pharmacological inhibitors revealed that activation of ADPR-cyclase by ANG II involved ANG II type 1 receptor, phosphoinositide 3-kinase, protein tyrosine kinase, and phospolipase C-γ1. Moreover, DHAB as well as 8-Br-cADPR abrogated ANG II-mediated Akt phosphorylation, nuclear translocation of nuclear factor of activated T cell, and uptake of [3H]thymidine and [3H]leucine in MMCs. These results demonstrate that ADPR-cyclase in MMCs plays a pivotal role in ANG II signaling for cell proliferation and protein synthesis.

scholarly journals Protease-Activated Receptor 1 Contributes to Angiotensin II-Induced Cardiovascular Remodeling and Inflammation

Cardiology ◽  
2016 ◽  
Vol 136 (4) ◽  
pp. 258-268 ◽  
Author(s):  
Silvio Antoniak ◽  
Jessica C. Cardenas ◽  
Laura J. Buczek ◽  
Frank C. Church ◽  
Nigel Mackman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Heart Function ◽  
Coronary Vessels ◽  
Wall Thickening ◽  
Ang Ii ◽  
Cardiovascular Remodeling ◽  
Protease Activated Receptor 1 ◽  
Pressure Independent ◽  
Fractional Shortening

Background: Angiotensin II (Ang II) plays an important role in cardiovascular disease. It also leads to the activation of coagulation. The coagulation protease thrombin induces cellular responses by activating protease-activated receptor 1 (PAR-1). We investigated whether PAR-1 contributes to Ang II-induced cardiovascular remodeling and inflammation. Methods and Results: PAR-1+/+ (wild-type; WT) and PAR-1-/- mice were infused with Ang II (600 ng/kg/min) for up to 4 weeks. In WT mice, this dose of Ang II did not cause a significant increase in blood pressure but it did cause pathological changes in both the aorta and the heart. Ang II infusion resulted in vascular remodeling of the aorta, demonstrated by a significant increase in medial wall thickening and perivascular fibrosis. Importantly, both parameters were significantly attenuated by PAR-1 deficiency. Furthermore, perivascular fibrosis around coronary vessels was reduced in Ang II-treated PAR-1-/- mice compared to WT mice. In addition, PAR-1 deficiency significantly attenuated Ang II induction of inflammatory cytokines and profibrotic genes in the aortas compared to WT mice. Finally, PAR-1 deficiency had no effect on Ang II-induced heart hypertrophy. However, the heart function measured by fractional shortening was less impaired in PAR-1-/- mice than in WT mice. Conclusion: Our data indicate that PAR-1 plays a significant role in cardiovascular remodeling mediated by a blood pressure-independent action of Ang II.

scholarly journals Eucommia ulmoidesOliv. (Du-Zhong) Lignans Inhibit Angiotensin II-Stimulated Proliferation by Affecting P21, P27, and Bax Expression in Rat Mesangial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xian Jing ◽  
Wei-Hua Huang ◽  
Yong-Jun Tang ◽  
Ya-Qin Wang ◽  
Hui Li ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cellular Proliferation ◽  
Mesangial Cells ◽  
Target Organ Damage ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Eucommia Ulmoides ◽  
Protective Effects ◽  
Ang Ii ◽  
Hypertensive Nephropathy

Cortex Eucommiae (Du-zhong) is the dried bark of theEucommia ulmoidesOliv. The natural products identified fromDu-zhonginclude lignans, iridoids, flavonoids, polysaccharides, terpenes, and proteins, Liu et al. (2012). Lignans, the main bioactive components, were protective against hypertensive renal injury in spontaneous hypertensive rats in our previous study, Li et al. (2012). Moreover,Eucommialignans also diminished aldose reductase (AR) overexpression in the kidney, Li et al. (2012). However, the pathological mechanism underlying the protective effects ofEucommialignans remains unknown. Cellular proliferation was reported to contribute to important pathological changes in hypertensive renal injuries, and increased angiotensin II (Ang II) expression was reported to be essential for target-organ damage during hypertension. Ang II is the main effective peptide in the renin-angiotensin system and is considered to be a key mediator in the development of hypertensive nephropathy, Rüster and Wolf (2011). Our preliminary results showed thatEucommialignans had inhibitory effects on Ang II-induced proliferation of rat mesangial cells. In the present study, we investigated the effects ofEucommia ulmoideson Ang II-induced proliferation and apoptosis of rat mesangial cells. Cell cycle-related genes P21 and P27, and cell apoptosis-related genes Bax and Bcl-2, were determined.

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