The Effect of Pravastatin on Expression of Platelet-Derived Endothelial Nitric Oxide Synthase(eNOS) m-RNA and Atherosclerosis Course in Rabbits.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3881-3881
Author(s):  
Liping Ma ◽  
Mafei Kang ◽  
Songmei Yin ◽  
Danian Nie ◽  
Shuangfen Xi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Atherosclerotic Plaques ◽  
Microscopic Features ◽  
Enos Mrna ◽  
Group A ◽  
Normal Production ◽  
Group B ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Common Carotid Arteries

Abstract Objective To observe changes of platelet-derived endothelial nitric oxide synthesase(eNOS) mRNA expression in hypercholesterolemia( HC) and atherosclerosis( AS) rabbits, and relationship between these changes and atherosclerosis regression and reversion. To probe into mechanism of pravastatin on preventing and improving pathological courses of AS. Methods 30 male New Zealand White rabbits were divided randomly into three groups, 12 in group A, 12 in group B, and 6 in group C. All of them were fed with cholesterol-riched food (1g cholesterol,10g pig fat) daily during the first 12 weeks. In addition, in group A, pravastatin (10mg) was orally administered daily. At end of the 12th week, 6 of in group A and B were killed randomly and their aortas were removed and pathologic changes were studied, such as thickness of fatty-streaks or atherosclerotic plaques. In following 12 weeks, food enriched with cholesterol was stopped and substituted with normal food in all three groups. Treatment with pravastatin was continued in remaining members of group A. Pravastatin TX was initiated in remaining members of group B. No additional medicine was given to group C. At end 24th week, all of rabbits were killed and their aortas were examined for same pathologic changes as above. The expression of eNOS mRNA, NO, the activity of NOS and the level of serum lipids were measured at different times (0 week, 12th week and 24th week). Results 1. The expressions of platelet-derived eNOS mRNA(2–4×108 platelet /ml) The expressions in group A were 0.739±0.364,0.992±0.539,0.1.019±0.280 at 0, 12th, 24thweeks, respectively (difference not significant).The expressions in group B were 0.952±0.768,0.490±0.245,1.00±0.774 (reduced significantly at 12 week compared with 0 week(P<0.01), but increased at 24th week compared with 12th week(P<0.05). The expression in group C were 0.816±0.163,0.327±0.285,0.186±0.117 (reduced at 12th week and 24th week compared with 0 week(P<0.05 and P<0.01).It was reduced in B group and C group compared with group A at 12 week(P<0.05) and was increased in A group and B group compared with C group at 24 week(P<0.01). 2. Pathologic appearances of the arteries In group A, the intima was smooth and glossy in all of aortas at the 12th and 24th weeks. While in group B, there were a lot of yellow-gray fatty-streaks in tentire intima of all large arteries at the 12th week. The fatty-streaks in ascending aorta, aorta arch and thoracic aorta were thicker and larger than those in abdominal aorta and common iliac arteries. There were annular plaques at opening of coronary arteries and common carotid arteries, bulgied into the cavity at the 24th week. In group C, there were marked plaques in entire aorta at the 24th week. 3. Microscopic features The fatty-streaks or atherosclerotic plaques thicken measured in percentage of vessel wall, were 0.035±0.023,0.325±0.175,0.765±0.143 at 0,12th,24th, respectively. Greater in group C compared with group A and group B at 24 week(P<0.01). Conclusions The down-regulated expression of platelet-derived eNOS mRNA in HC or AS rabbits might be one of important causes in initiation and development of AS. Pravastatin can up-regulate expression of platelet-derived eNOS mRNA and NOS activity, and maintain normal production of NO. This leads to improvement of pathologic appearances or microscopic features of AS.

scholarly journals Phytoestrogenic Effects of Blackcurrant Anthocyanins Increased Endothelial Nitric Oxide Synthase (eNOS) Expression in Human Endothelial Cells and Ovariectomized Rats

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1259 ◽  
Author(s):  
Kayo Horie ◽  
Naoki Nanashima ◽  
Hayato Maeda
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Nitric Oxide Synthase ◽  
Mrna Levels ◽  
Human Endothelial Cells ◽  
Enos Expression ◽  
Ovx Rats ◽  
Enos Mrna ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Phytoestrogens are plant-derived chemicals that are found in many foods and have estrogenic activity. We previously showed that blackcurrant extract (BCE) and anthocyanins have phytoestrogenic activity mediated via estrogen receptors (ERs), and anthocyanins may improve vascular function. BCE contains high levels of anthocyanins, but their health-promoting effects are unclear. This study examined the effects of BCE on the regulation of endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis in human endothelial cells as key regulators in cardiovascular disease. The results showed that eNOS mRNA levels were significantly upregulated in BCE- or anthocyanin-treated human vascular endothelial cells but decreased in cells treated with fulvestrant, an ER antagonist. These results corresponded with NO levels, suggesting that BCE and anthocyanin may regulate NO synthesis via eNOS expression. Thus, the phytoestrogenic effects exerted by BCE via ERs influenced eNOS mRNA expression and NO synthesis. In vivo, we investigated whether anthocyanin-rich BCE upregulated eNOS protein expression in ovariectomized (OVX) rats, a widely used animal model of menopause. Our results showed that anthocyanin-rich BCE significantly upregulated eNOS mRNA levels and NO synthesis through phytoestrogenic activity and therefore promoted blood vessel health in OVX rats as a postmenopausal model.

Retinoic acid suppression of endothelial nitric oxide synthase in porcine oocyte

2002 ◽  
Vol 80 (8) ◽  
pp. 777-782 ◽  
Author(s):  
Masa-aki Hattori ◽  
Yukio Kato ◽  
Noboru Fujihara
Keyword(s):  
Nitric Oxide ◽  
Retinoic Acid ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Mrna Level ◽  
Dependent Manner ◽  
Hormonal Stimulation ◽  
Enos Mrna ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The presence of endothelial nitric oxide synthase (eNOS) has been found in porcine oocytes, but its mRNA and protein levels remain relatively constant during hormonal stimulation. The present study was designed to determine the effect of retinoic acid on eNOS regulation in porcine oocytes during follicle-stimulating hormone (FSH) stimulation. Cumulus–oocyte complexes (COCs), prepared from small antral follicles of immature porcine ovaries, were cultured for 15 h and treated with FSH for an additional 48 h. eNOS mRNA and its protein were analyzed by reverse transcription – polymerase chain reaction and Western blotting, respectively. Retinoic acid had an inhibitory effect on the level of oocyte eNOS mRNA in a dose-dependent manner if COCs were exposed to retinoic acid before FSH stimulation. The inhibition of FSH action was reflected in a decrease in expression of c-fos mRNA. eNOS protein also decreased to approximately 50% of the control after exposure to 10 μM retinoic acid. However, the ability of NO synthesis was abolished in the oocytes prepared from retinoic acid pretreated COCs. These results suggest that retinoic acid has a strong inhibitory action on eNOS mRNA level and NO synthesis in the porcine oocyte.Key words: oocyte, retinoic acid, NO synthesis, eNOS, RT–PCR.

Expression of endothelial nitric oxide synthase in the postnatal developing porcine kidney

2001 ◽  
Vol 280 (5) ◽  
pp. R1269-R1275 ◽  
Author(s):  
Michael J. Solhaug ◽  
Usa Kullaprawithaya ◽  
Xui Q. Dong ◽  
Ke-Wen Dong
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Protein Content ◽  
Endothelial Nitric Oxide Synthase ◽  
Enos Expression ◽  
Developmentally Regulated ◽  
Enos Mrna ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Enos Protein

The postnatal pattern of renal endothelial nitric oxide synthase (eNOS) is unknown. The purpose of this study was to characterize eNOS expression during maturation and compare this to neuronal NOS (nNOS). The experiments measured whole kidney eNOS mRNA expression by RT-PCR and protein content by Western blot, as well as cortical and medullary protein content in piglets at selected postnatal ages and in adult pigs. Whole kidney eNOS mRNA was compared with nNOS. Whole kidney eNOS expression decreased from the newborn to its lowest at 7 days, returning by 14 days to adult levels. This eNOS mRNA pattern contrasted with nNOS, which was highest at birth, and progressively decreased to its lowest level in the adult. At birth, cortical eNOS protein was greater than medullary, contrasting with the adult pattern of equivalent levels. In conclusion eNOS is developmentally regulated during early renal maturation and may critically participate in renal function during this period. The eNOS developmental pattern differs from nNOS, suggesting that these isoforms may have different regulatory factors and functional contributions in the postnatal kidney.

Endothelial nitric oxide synthase Glu298→Asp polymorphism, carotid atherosclerosis and intima-media thickness in a general population sample

2005 ◽  
Vol 109 (5) ◽  
pp. 475-481 ◽  
Author(s):  
Birger Wolff ◽  
Claudia Braun ◽  
Christina Schlüter ◽  
Hans J. Grabe ◽  
Katrin Popowski ◽  
...  
Keyword(s):  
Endothelial Nitric Oxide Synthase ◽  
Carotid Arteries ◽  
Carotid Atherosclerosis ◽  
Intima Media Thickness ◽  
Atherosclerotic Plaques ◽  
Carotid Imt ◽  
The Common ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Common Carotid Arteries

The Glu298→Asp (E298D; 894G→T) polymorphism of eNOS (endothelial nitric oxide synthase) has been related with cardiovascular disease. In the present study, we investigated the association of Glu298→Asp with atherosclerotic plaques in different carotid vessel segments and with carotid IMT (intima-media thickness). The Glu298→Asp eNOS polymorphism was determined by 5′-exonuclease assay among 2448 participants of the SHIP (Study of Health in Pomerania). Mean and maximum common carotid IMT, as well as carotid atherosclerosis, were measured by high-resolution ultrasound. The Asp/Asp298 genotype was associated with an increased risk of atherosclerotic plaques at the level of the common carotid arteries [multivariate odds ratio, 1.57 and 95% CI (confidence interval), 1.05–2.34; P=0.025], but not in the carotid bifurcations or internal or external carotid arteries. Glu298→Asp genotype was not associated with carotid IMT in the whole sample. However, the Asp/Asp298 genotype was independently associated with both higher mean [adjusted increase by 0.046 mm (95% CI, 0.013–0.078); P=0.006] and maximum carotid IMT [0.137 mm (95% CI, 0.064–0.209); P<0.001] in the low-risk group of subjects without carotid atherosclerosis. In conclusion, the Asp/Asp298 genotype is associated with atherosclerosis in the common carotid arteries and, in a low-risk group, also with carotid IMT. This suggests that the association of the Glu298→Asp genotype with atherosclerosis in the carotid arteries is site-specific and is modified by overall cardiovascular risk.

scholarly journals Disrupted NOS signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow

2016 ◽  
Vol 311 (1) ◽  
pp. H137-H145 ◽  
Author(s):  
Sanjeev A. Datar ◽  
Wenhui Gong ◽  
Youping He ◽  
Michael Johengen ◽  
Rebecca J. Kameny ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Nitric Oxide Synthase ◽  
Lymph Flow ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Circulation ◽  
Enos Mrna ◽  
No Signaling ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Associated abnormalities of the lymphatic circulation are well described in congenital heart disease. However, their mechanisms remain poorly elucidated. Using a clinically relevant ovine model of a congenital cardiac defect with chronically increased pulmonary blood flow (shunt), we previously demonstrated that exposure to chronically elevated pulmonary lymph flow is associated with: 1) decreased bioavailable nitric oxide (NO) in pulmonary lymph; and 2) attenuated endothelium-dependent relaxation of thoracic duct rings, suggesting disrupted lymphatic endothelial NO signaling in shunt lambs. To further elucidate the mechanisms responsible for this altered NO signaling, primary lymphatic endothelial cells (LECs) were isolated from the efferent lymphatic of the caudal mediastinal node in 4-wk-old control and shunt lambs. We found that shunt LECs ( n = 3) had decreased bioavailable NO and decreased endothelial nitric oxide synthase (eNOS) mRNA and protein expression compared with control LECs ( n = 3). eNOS activity was also low in shunt LECs, but, interestingly, inducible nitric oxide synthase (iNOS) expression and activity were increased in shunt LECs, as were total cellular nitration, including eNOS-specific nitration, and accumulation of reactive oxygen species (ROS). Pharmacological inhibition of iNOS reduced ROS in shunt LECs to levels measured in control LECs. These data support the conclusion that NOS signaling is disrupted in the lymphatic endothelium of lambs exposed to chronically increased pulmonary blood and lymph flow and may contribute to decreased pulmonary lymphatic bioavailable NO.

scholarly journals The Role of e-NOS in Chronic Cholestasis-Induced Liver and Renal Injury in Rats: The Effect of N-Acetyl Cysteine

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yusuf Gunay ◽  
Semsi Altaner ◽  
Nergiz Ekmen
Keyword(s):  
Liver Injury ◽  
Sham Group ◽  
Kidney Injury ◽  
Chronic Cholestasis ◽  
Liver And Kidney ◽  
Group A ◽  
Group B ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Introduction.The role of chronic cholestasis (CC) in liver injury and fibrosis remains unclear. The aims of this study were to define the role of endothelial nitric oxide synthase (e-NOS) in CC and the protective effect of N-acetyl-L-cysteine (NAC) in liver and kidney injury.Materials and Methods.Group A (sham group); Group B (CBDL); and Group C (CBDL + NAC). Group C received daily dosage of NAC (100 mg/kg) intraperitoneally for up to 4 weeks.Results.The rate of bridging fibrosis was higher (100% versus 20%,P=.025), but the intensity of e-NOS in liver was lower in rats that received NAC (1.3 versus 2.7,P=.046). The necrotic area in the kidneys among rats that received NAC was lower at week 4 (48% versus 57%;P<.001). The numbers of e-NOS stained cells in kidney were similar in sham group and the two groups with CBDL.Discussion.NAC reduced the stimulus for liver fibrosis in this rat model of CC and attenuated liver and kidney injury. Our study showed that e-NOS expression increased in liver tissue of rats with CC and that this was reversed by NAC. Treatment with NAC might restore e-NOS protein expression and prevent liver injury in CC.

scholarly journals Resistin decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells

2010 ◽  
Vol 299 (1) ◽  
pp. H193-H201 ◽  
Author(s):  
Changyi Chen ◽  
Jun Jiang ◽  
Jian-Ming Lü ◽  
Hong Chai ◽  
Xinwen Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Superoxide Dismutase ◽  
Coronary Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Human Coronary Artery ◽  
Enos Mrna ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Resistin is a newly discovered adipocyte-derived cytokine that may play an important role in insulin resistance, diabetes, adipogenesis, inflammation, and cardiovascular disease. However, it is largely unknown whether resistin impairs endothelial functions by affecting the endothelial nitric oxide synthase (eNOS) system. In this study, we determined the effect of human recombinant resistin protein on eNOS expression and regulation in human coronary artery endothelial cells (HCAECs). When cells were treated with clinically relevant concentrations of resistin (40 or 80 ng/ml) for 24 h, the levels of eNOS mRNA, protein, and activity and eNOS mRNA stability were significantly reduced. Cellular nitric oxide levels were also decreased. In addition, the cellular levels of reactive oxygen species (ROS), including superoxide anion, were significantly increased in resistin-treated HCAECs. Mitochondrial membrane potential and the activities of catalase and superoxide dismutase were reduced. Three antioxidants, seleno-l-methionine, ginsenoside Rb1, and MnTBAP (superoxide dismutase mimetic), effectively blocked resistin-induced eNOS downregulation. Meanwhile, resistin activated the mitogen-activated protein kinases p38 and c-Jun NH2-terminal kinase (JNK), and the specific p38 inhibitor SB-239063 effectively blocked resistin-induced ROS production and eNOS downregulation. Furthermore, immunoreactivity of resistin was increased in atherosclerotic regions of human aorta and carotid arteries. Thus resistin directly induces eNOS downregulation through overproduction of ROS and activation of p38 and JNK in HCAECs. Resistin-induced mitochondrial dysfunction and imbalance in cellular redox enzymes may be the underlying mechanisms of oxidative stress.

scholarly journals Ferulic Acid Alleviates Atherosclerotic Plaques by Inhibiting VSMC Proliferation Through the NO/p21 Signaling pathway

2022 ◽  
Author(s):  
Xiaoyun Wu ◽  
Ziwei Hu ◽  
Junjie Zhou ◽  
Jin Liu ◽  
Ping Ren ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ferulic Acid ◽  
Blood Lipid ◽  
Atherosclerotic Plaques ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Proliferation And Migration ◽  
Blood Lipid Levels

Abstract The benefits and risks of inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) remain a subject of debate. In this study, we investigated the effect of ferulic acid (FA) on the proliferation and migration of VSMCs induced by platelet-derived growth factor (PDGF) and the associated mechanism and used ApoE-/- mice to study whether the effect of FA on VSMC proliferation and migration is beneficial in alleviating AS plaques. It was found that FA not only reduced blood lipid levels but also promoted the production of nitric oxide (NO) by MOVAS cells through the endothelial nitric oxide synthase (eNOS) pathway, inhibited the migration and proliferation of VSMCs induced by PDGF, promoted the expression of p21 in VSMCs, and exerted a therapeutic effect against AS.

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