scholarly journals Circulating Concentrations of Key Regulators of Nitric Oxide Production in Undernourished Sheep Carrying Single and Multiple Fetuses

Animals ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 65 ◽  
Author(s):  
Fiammetta Berlinguer ◽  
Cristian Porcu ◽  
Giovanni Molle ◽  
Andrea Cabiddu ◽  
Maria Dattena ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Amino Acids ◽  
Energy Restriction ◽  
Energy Requirements ◽  
Control Group ◽  
No Production ◽  
Blood Concentrations ◽  
Dietary Energy Restriction ◽  
Twin Pregnancies ◽  
Singleton Pregnancies

The aim of this study was to investigate the blood concentrations of L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine, which are regulators of nitric oxide (NO) synthesis, in single, twin, and triplet pregnancies in ewes undergoing either a dietary energy restriction or receiving 100% of their energy requirements. From day 24 to 100 of pregnancy, the ewes were fed ryegrass hay and two different iso-proteic concentrates fulfilling either 100% of ewes’ energy requirements (control group; n = 30, 14 singleton pregnancies, 12 twin pregnancies, and 4 triplet pregnancies) or only 45% (feed-restricted group; n = 29; 11 singleton pregnancies, 15 twin pregnancies, and 3 triplet pregnancies). Blood samples were collected monthly to measure, by capillary electrophoresis, the circulating concentrations of arginine, ADMA, homoarginine, SDMA, and of other amino acids not involved in NO synthesis to rule out possible direct effects of diet restriction on their concentrations. No differences between groups were observed in the circulating concentrations of most of the amino acids investigated. L-homoarginine increased markedly in both groups during pregnancy (p < 0.001). SDMA (p < 0.01), L-arginine, and ADMA concentrations were higher in feed-restricted ewes than in controls. The L-arginine/ADMA ratio, an indicator of NO production by NOS, decreased towards term without differences between groups. The ADMA/SDMA ratio, an index of the ADMA degrading enzyme activity, was higher in controls than in feed-restricted ewes (p < 0.001). Obtained results show that circulating concentrations of L-arginine, of its metabolites, and the ratio between NO synthesis boosters and inhibitors are altered in energy-restricted ewes, and that these alterations are more marked in ewes carrying multiple fetuses.

Renal and pressor effects of aminoguanidine in cirrhotic rats with ascites.

1996 ◽  
Vol 7 (12) ◽  
pp. 2694-2699
Author(s):  
M C Ortíz ◽  
L A Fortepiani ◽  
C Martínez ◽  
N M Atucha ◽  
J García-Estañ
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Liver Cirrhosis ◽  
Experimental Model ◽  
Systemic Blood Pressure ◽  
Arterial Hypotension ◽  
Control Group ◽  
No Production ◽  
Water Excretion ◽  
Excretory Function

Recent work indicates that nitric oxide (NO) plays an important role in the systemic and renal alterations of liver cirrhosis. This study used aminoguanidine (AG), a preferential inhibitor of inducible nitric oxide synthase (iNOS), to evaluate the role of this NOS isoform in the systemic and renal alterations of an experimental model of liver cirrhosis with ascites (carbon tetrachloride/ phenobarbital). Experiments have been performed in anesthetized cirrhotic rats and their respective control rats prepared for clearance studies. Administration of AG (10 to 100 mg/kg, iv) elevated dose-dependent mean arterial pressure (MAP, in mm Hg) in the cirrhotic rats from a basal level of 79.3 +/- 3.6 to 115.0 +/- 4.7, whereas in the control animals, MAP increased only with the highest dose of the inhibitor (from 121.8 +/- 3.6 to 133.3 +/- 1.4). In the cirrhotic group, AG also significantly increased sodium and water excretion, whereas these effects were very modest in the control group. Plasma concentration of nitrates+nitrites, measured as an index of NO production, were significantly increased in the cirrhotic animals in the basal period and decreased with AG to levels not significantly different from the control animals. Similar experiments performed with the nonspecific NOS inhibitor N omega-nitro-L-arginine (NNA) also demonstrated an increased pressor sensitivity of the cirrhotic rats, but the arterial hypotension was completely corrected. These results, in an experimental model of liver cirrhosis with ascites, show that AG exerts a beneficial effect as a result of inhibition of NO production, increasing blood pressure and improving the reduced excretory function. Because NNA, but not AG, completely normalized the arterial hypotension, it is suggested that the constitutive NOS isoform is also contributing in an important degree. It is concluded that the activation of both inducible and constitutive NOS isoforms plays an important role in the lower systemic blood pressure and associated abnormalities that characterize liver cirrhosis.

Endothelial nitric oxide production during in vitro simulation of external limb compression

2002 ◽  
Vol 282 (6) ◽  
pp. H2066-H2075 ◽  
Author(s):  
Guohao Dai ◽  
Olga Tsukurov ◽  
Michael Chen ◽  
Jonathan P. Gertler ◽  
Roger D. Kamm
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Umbilical Vein ◽  
Control Group ◽  
No Production ◽  
Vein Thrombosis ◽  
Enos Mrna ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Nitric Oxide

External pneumatic compression (EPC) is effective in preventing deep vein thrombosis (DVT) and is thought to alter endothelial thromboresistant properties. We investigated the effect of EPC on changes in nitric oxide (NO), a critical mediator in the regulation of vasomotor and platelet function. An in vitro cell culture system was developed to simulate flow and vessel collapse conditions under EPC. Human umbilical vein endothelial cells were cultured and subjected to tube compression (C), pulsatile flow (F), or a combination of the two (FC). NO production and endothelial nitric oxide synthase (eNOS) mRNA expression were measured. The data demonstrate that in the F and FC groups, there is a rapid release of NO followed by a sustained increase. NO production levels in the F and FC groups were almost identical, whereas the C group produced the same low amount of NO as the control group. Conditions F and FC also upregulate eNOS mRNA expression by a factor of 2.08 ± 0.25 and 2.11 ± 0.21, respectively, at 6 h. Experiments with different modes of EPC show that NO production and eNOS mRNA expression respond to different time cycles of compression. These results implicate enhanced NO release as a potentially important factor in the prevention of DVT.

Amino acids as modulators of endothelium-derived nitric oxide

2006 ◽  
Vol 291 (2) ◽  
pp. F297-F304 ◽  
Author(s):  
Masao Kakoki ◽  
Hyung-Suk Kim ◽  
Cora-Jean S. Edgell ◽  
Nobuyo Maeda ◽  
Oliver Smithies ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Amino Acids ◽  
Endothelial Cells ◽  
Cultured Cells ◽  
Rat Kidney ◽  
No Production ◽  
Renal Vasculature ◽  
Cationic Amino Acid ◽  
Neutral Amino Acids ◽  
Cationic Amino Acids

To examine the mechanisms whereby amino acids modulate nitric oxide (NO) production and blood flow in the renal vasculature, chemiluminescence techniques were used to quantify NO in the renal venous effluent of the isolated, perfused rat kidney as different amino acids were added to the perfusate. The addition of 10−4 or 10−3 M cationic amino acids (l-ornithine, l-lysine, or l-homoarginine) or neutral amino acids (l-glutamine, l-leucine, or l-serine) to the perfusate decreased NO and increased renal vascular resistance. Perfusion with anionic amino acids (l-glutamate or l-aspartate) had no effect on either parameter. The effects of the cationic and neutral amino acids were reversed with 10−3 M l-arginine and prevented by deendothelialization or NO synthase inhibition. The effects of the neutral amino acids but not the cationic amino acids were dependent on extracellular sodium. Cationic and neutral amino acids also decreased calcimycin-induced NO, as assessed by DAF-FM-T fluorescence, in cultured EA.hy926 endothelial cells. Inhibition of system y+ or y+L by siRNA for the cationic amino acid transporter 1 or the CD98/4F2 heavy chain diminished the NO-depleting effects of these amino acids. Finally, transport studies in cultured cells demonstrated that cationic or neutral amino acids in the extracellular space stimulate efflux of l-arginine out of the cell. Thus the present experiments demonstrate that cationic and neutral amino acids can modulate NO production in endothelial cells by altering cellular l-arginine transport through y+ and y+L transport mechanisms.

Variations in the Platelet Arginine/Nitric Oxide Pathway during the Ovarian Cycle in Females Affected by Menstrual Migraine

Cephalalgia ◽  
1996 ◽  
Vol 16 (7) ◽  
pp. 468-475 ◽  
Author(s):  
P Sarchielli ◽  
M Tognoloni ◽  
S Russo ◽  
MR Vulcano ◽  
M Feleppa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Luteal Phase ◽  
Human Platelets ◽  
Menstrual Migraine ◽  
Control Group ◽  
No Production ◽  
Platelet Response ◽  
Patient Groups ◽  
Oxide Synthase ◽  
Age Range

Previous studies have reported the existence of an arginine/nitric oxide (NO) pathway and the involvement of a Ca2+, NADPH-dependent nitric oxide synthase enzyme (NOS) in the generation of NO in human platelets. In the present research, we determined the rate of production of NO and cGMP in the cytosol of platelets stimulated by collagen in 20 females with menstrual migraine (MM), (age range 2440 years), assessed in the follicular and luteal phases, interictally and ictally in the latter period. The same patients were also assessed at mid-cycle. At the same time, the variations in the collagen response of platelets were evaluated. Moreover, these parameters were determined in the same periods in 20 age-matched control females and in 20 females affected by non-menstrually related migraine (nMM). The collagen-stimulated production of NO in the cytosol of the platelet cytosol was significantly higher in migraine patients with MM than in the control subjects. In MM patients, the increase was greater in the luteal phase of the cycle than during the follicular phase ( p<0.005). A rise in NO production in platelets was also present, although to a lesser extent, in females affected by nMM compared to the healthy females, but this rise was most evident at ovulation ( p<0.001). A slight but significant increase was also observed at mid-cycle in control women, but this increase did not reach the values determined in the migraine groups ( p<0.02). NO production in platelets stimulated by collagen was significantly increased during attacks with respect to the interictal period in both patient groups. Similar variations were observed in the production of cGMP in MM and nMM patients. The increase in NO production was accompanied by a decrease in platelet aggregation in the migraine groups compared with the control group; this decrease was most evident at mid-cycle in nMM patients and in the luteal phase in MM patients. These data suggest an activation of the L-arginine/ NO pathway in MM and nMM patients which could explain the modifications in the platelet response to collagen evidenced in migraine-free periods and during attacks. The activation of this pathway is more accentuated in the luteal phase in MM patients, and this could be the cause of the increased susceptibility to migraine attacks in premenstrual and menstrual periods in these patients.

scholarly journals Quiescence/Mobilization of Hematopoietic Immature Cells Induced By Polyphenols through Modulation of APC/EPCR/PAR-1 Axis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4996-4996
Author(s):  
Cristiane Okuda Torello ◽  
Erich V De Paula ◽  
Rodrigo Naoto Shiraishi ◽  
Santos Irene ◽  
Fernanda I Della Via ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Bone Marrow ◽  
Vascular Permeability ◽  
Functional Ability ◽  
Bone Marrow Cells ◽  
Control Group ◽  
No Production ◽  
Enos Phosphorylation ◽  
Immature Cells

The mechanism underlying quiescence and/or mobilization of hematopoietic stem cells and their bone marrow progenitors (HSPC) into circulation are tightly regulated for the continuous supply of peripheral blood cells; however, non-physiological or stress conditions, such as infections, can accelerate these mechanisms. Our results have shown that polyphenols modulate quiescence/mobilization of HSPC, but do not affect mature populations. Thrombin has been reported to induce the rapid HSPC mobilization through coagulation thrombin/PAR-1 axis, and quiescence is maintained across the APC/EPCR/PAR-1 axis (Nat. Med. 2015, 21:1307-17). Our objective was to investigate the effect of polyphenols on thrombin/PAR-1 and APC/EPCR/PAR-1 axis. C57BL/6J mice (6-8 weeks old) were treated with polyphenols from green tea extract (250 mg/kg body weight) orally (gavage) once every seven days and injected (i.p.) at day 7 with lipopolysaccharide (LPS) (100μg;Sigma) (n=6). The control group received vehicle and was injected with LPS (n=6). After 24h of LPS injection, mice were anesthetized for blood collection, and then sacrificed for bone marrow collection. PAR-1 and EPCR expression, nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) phosphorylation were evaluated in HSPC by flow cytometry. The functional ability of HSC was assessed by competitive repopulation assay. Vascular permeability was studied using Evans blue. After LPS injection, mice showed reduced expression of EPCR in bone marrow LSK parallel to an increase of PAR-1 expression in circulating immature and mature cells. Treatment of these mice with polyphenols partially prevented the reduced expression of EPCR in bone marrow LSK (13±3 vs 54±12; p<0.05), but did not affect the increased PAR-1 expression in circulating immature and mature cells. Evans blue assay revealed a reduction in the vascular permeability of the bone marrow of LPS-injected mice treated with polyphenols (3.9±0.5 vs 2.1±0.1; p<0.05). To assess whether polyphenols altered NO production, we measured NO levels and eNOS phosphorylation in immature LSK EPCRhigh (or LT-HSC) cells. NO production is activated by eNOS phosphorylation at Ser1177 and negatively regulated by eNOS phosphorylation at Thr495. LPS injection rapidly increased NO levels and eNOS phosphorylation at Ser1177 in bone marrow LSK of mice. Treatment of these mice with polyphenols reduced the percentage of bone marrow LSK EPCRhigh cells with higher intracellular NO (52±2.8 vs 28±5.6; p<0.01) and increased eNOS phosphorylation at Thr495 in immature LSK. In order to evaluate the action of polyphenols on the functional ability of HSC, a competitive bone marrow repopulation assay was performed. Donor mice (C57BL/6J) received or not polyphenols followed by LPS injection (treated group: Polyphenols+LPS; control group: LPS), and bone marrow cells were transplanted (1:1) together with bone marrow cells of competitors (B6.SJL-PtprcaPepcb/BoyJ) in lethally irradiated recipients (B6.SJL-PtprcaPepcb/BoyJ). Mice were followed for 16 weeks and hematological analysis revealed no difference in circulating leukocytes, platelets or hemoglobin levels. Transplanted mice (recipients) presented a higher percentage of CD45+ cells from Polyphenols+LPS donors (33.7±13 vs 78.6±0.9; p<0.05) in the peripheral blood, as well as increased number of T lymphocytes (6.7±4.5 vs 37.2±2.9; p<0.05) and myeloid cells (68.5±1.7 vs 82.5±3.5; p<0.05) from Polyphenols+LPS group. After 16 weeks, mice were euthanized and a higher percentage of LSK (or HSC) and LSK EPCRhigh (or LT-HSC) cells from Polyphenols+LPS donors were detected in the bone marrow, although only the percentage of LSK EPCRhigh was statistically different (0.0014±0.0001 vs 0.0032±0.001; p<0.05). Taken together, our results indicate that polyphenols increased the functional ability of HSC in LPS-injected mice showing increased percentage of bone marrow LSK EPCRhigh cells, which are the most quiescent stem cells with strong self-renewal ability. Polyphenols reduced EPCR expression and NO production in immature cells of LPS-injected mice, exhibiting an anti-inflammatory effect that leads to the maintenance of barrier integrity and quiescence of cells, which was corroborated by reducing vascular permeability in the bone marrow. Thus, polyphenols appear to modulate quiescence/mobilization of HSPC through APC/EPCR/PAR-1 axis. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Protective Effects of Chronic Intermittent Hypobaric Hypoxia Against Osteoarthritis in Rats - Role of Nitric Oxide

2021 ◽  
Author(s):  
Tianci Wang ◽  
Dong Ren ◽  
Yunshan Su ◽  
Jian Lu ◽  
Ming Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hypobaric Hypoxia ◽  
Meniscal Tear ◽  
Cartilage Degeneration ◽  
Joint Fluid ◽  
Control Group ◽  
No Production ◽  
Protective Effects ◽  
Blank Control Group ◽  
Intermittent Hypobaric Hypoxia

Abstract The study explored the effect of chronic intermittent hypobaric hypoxia (CIHH) on osteoarthritis (OA). CIHH conditioning was realized by exposing rats to hypobaric hypoxia environment mimicking 5,000 m high-altitude (PB=404 mmHg, PO2=84 mmHg) 6 h per day, once daily for 28 days. OA model was induced by surgically-induced medial meniscal tear. Male Wistar rats were randomly assigned into 5 groups: preconditioning group （CIHH + OA）, postconditioning group （OA + CIHH）, control group, inhibitor group [OA + inducible nitric oxide synthase (iNOS) inhibitor], blank control group. The expression iNOS, nitric oxide (NO) content levels in the joint fluid were measured at 1, 2, 3 weeks after the OA modelling. Results revealed that OA modelling induced cartilage degeneration, up-regulated iNOS expression, increased joint fluid NO content. CIHH preconditioning and postconditioning reduced cartilage degeneration, prevented the NO production. Inhibitor groups showed alleviated joint degeneration than control group, but not as effective as CIHH condition. These results suggest that both CIHH preconditioning and postconditioning plays a protective role on OA, one of the mechanism was inhibiting the overexpression of iNOS and NO production.

scholarly journals EVALUATION OF THE STATUS OF SALIVARY NITRIC OXIDE IN PATIENTS WITH DENTAL CARIES

2012 ◽  
Vol 02 (02) ◽  
pp. 06-09 ◽  
Author(s):  
Mithra N. Hegde ◽  
Suchetha Kumari ◽  
Nidarsh Hegde ◽  
Shilpa Shetty ◽  
Keyword(s):  
Nitric Oxide ◽  
Dental Caries ◽  
Risk Group ◽  
Saliva Sample ◽  
High Risk Group ◽  
Control Group ◽  
No Production ◽  
High Caries Risk ◽  
The Status

AbstractThe aim of the present study is to evaluate the status of salivary nitric oxide in patients with dental caries. The study consisted of 80 individuals. According to DFMT index, the subjects were divided into control group (DMFT=0) and study group (DMFT>5). Saliva sample was collected from each subject. Nitric oxide concentration was measured as total nitrates and nitrites by the Griess reaction method. The results of this study show that the presence of NO and its metabolites in saliva of adults with natural healthy teeth is significantly higher compared to high risk group, suggesting the protective role of NO in relation to caries. From the study it can be concluded that highly significant increase of nitrates and nitrites in stimulated saliva of high caries risk group could be the host defense response opposing bacterial growth. The obtained results support the role of NO as modulator of bacterial proliferation and suggest that increased NO production might contribute to lower caries incidence in adults.

scholarly journals Four New Iridoid Metabolites Have Been Isolated from the Stems of Neonauclea reticulata (Havil.) Merr. with Anti-Inflammatory Activities on LPS-Induced RAW264.7 Cells

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4271
Author(s):  
Fang-Pin Chang ◽  
Shyh-Shyun Huang ◽  
Tzong-Huei Lee ◽  
Chi-I Chang ◽  
Tzong-Fu Kuo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Detailed Analysis ◽  
Cell Line ◽  
Spectroscopic Data ◽  
Protocatechuic Acid ◽  
Control Group ◽  
No Production ◽  
Raw264.7 Macrophages ◽  
Ic50 Values ◽  
Inhibitory Activities

One new iridoid, namely neonanin C (1) one monocyclic iridoid ring-opened derivative namely neonanin D (2), two new bis-iridoid derivatives namely reticunin A (3) and reticunin B (4) with sixteen known compounds (5–20) were isolated from the stems of Neonauclea reticulata (Havil.) Merr. These new structures were determined by the detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1–20 were evaluated for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages cell line. The results showed that all compounds exhibited no obvious cytotoxicity compared to the control group and five compounds including isoboonein (7), syringaresinol (10), (+)-medioresinol (12), protocatechuic acid (14) and trans-caffeic acid (15) exhibited inhibitory activities with IC50 values at 86.27 ± 3.45; 9.18 ± 1.90; 76.18 ± 2.42; 72.91 ± 4.97 and 95.16 ± 1.20 µg/mL, respectively.

scholarly journals Protective Effects of Bacillus amyloliquefaciens 40 Against Clostridium perfringens Infection in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Zipeng Jiang ◽  
Wentao Li ◽  
Weifa Su ◽  
Chaoyue Wen ◽  
Tao Gong ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Clostridium Perfringens ◽  
Relative Abundance ◽  
Bacillus Amyloliquefaciens ◽  
Infected Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
No Production ◽  
Mrna Levels ◽  
Protective Effects

This study aimed to investigate the protective effects of Bacillus amyloliquefaciens (BA40) against Clostridium perfringens (C. perfringens) infection in mice. Bacillus subtilis PB6 was utilized as a positive control to compare the protective effects of BA40. In general, a total of 24 5-week-old male C57BL/6 mice were randomly divided into four groups, with six mice each. The BA40 and PB6 groups were orally dosed with resuspension bacteria (1 × 109 CFU/ml) once a day, from day 1 to 13, respectively. In the control and infected groups, the mice were orally pre-treated with phosphate-buffered saline (PBS) (200 μl/day). The mice in the infected groups, PB6 + infected group and BA40 + infected group, were orally challenged with C. perfringens type A (1 × 109 CFU/ml) on day 11, whereas the control group was orally dosed with PBS (200 μl/day). The results showed that the BA40 group ameliorated intestinal structure damage caused by the C. perfringens infection. Furthermore, the inflammatory responses detected in the infected groups which include the concentrations of IL-1β, TNF-α, IL-6, and immunoglobulin G (IgG) in the serum and secretory immunoglobulin (SigA) in the colon, and nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity in the jejunum, were also alleviated (P &lt; 0.05) by BA40 treatment. Similarly, cytokines were also detected by quantitative PCR (qPCR) in the messenger RNA (mRNA) levels, and the results were consistent with the enzyme-linked immunosorbent assay (ELISA) kits. Additionally, in the infected group, the mRNA expression of Bax and p53 was increasing and the Bcl-2 expression was decreasing, which was reversed by BA40 and PB6 treatment (P &lt; 0.05). Moreover, the intestinal microbiota imbalance induced by the C. perfringens infection was restored by the BA40 pre-treatment, especially by improving the relative abundance of Verrucomicrobiota (P &lt; 0.05) and decreasing the relative abundance of Bacteroidetes (P &lt; 0.05) in the phyla level, and the infected group increased the relative abundance of some pathogens, such as Bacteroides and Staphylococcus (P &lt; 0.05) in the genus level. The gut microbiota alterations in the BA40 group also influenced the metabolic pathways, and the results were also compared. The purine metabolism, 2-oxocarboxylic acid metabolism, and starch and sucrose metabolism were significantly changed (P &lt; 0.05). In conclusion, our results demonstrated that BA40 can effectively protect mice from C. perfringens infection.

Abstract 13480: High Density Lipoprotein Promotes Angiogenesis by Suppressing Mir-24-3p Expression

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Zhijun OU ◽  
Hua-Ming Li ◽  
Zhi-Wei Mo ◽  
Yue-Ming Peng ◽  
Yan Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
High Density Lipoprotein ◽  
Umbilical Vein ◽  
Density Lipoprotein ◽  
Tube Formation ◽  
High Density ◽  
Control Group ◽  
No Production ◽  
Mirnas Expression

Introduction: Previous studies showed that high density lipoprotein (HDL) can stimulate angiogenesis. However, the mechanisms by which HDL promotes angiogenesis remains unclear. Hypothesize: HDL may promote angiogenesis by regulating miRNAs expression. Methods: HDL was isolated from healthy subjects. Human umbilical vein endothelial cells (HUVECs) were cultured with vehicle or HDL (100 μg/ml), and the differential miRNAs expression were indentified by miRNA array and verified by qRT-PCR. HUVECs were treated with vehicle or HDL (100 μg/ml) with or without miRNAs mimic, endothelial cells proliferation, migration and tube formation were detected. The production of nitric oxide(NO) was measured. The expression and phosphorylation of endothelial nitric oxide synthase (eNOS) was determined. Results: The miRNAs profile of HDL-treated HUVECs is significantly different from control group. HDL significantly downregulated miR-24-3p expression. HDL significantly promoted HUVECs proliferation, migration and tube formation. HDL also significantly stimulated NO production and up-regulated the expression and phosphorylation of eNOS. However, HDL did not stimulated HUVECs proliferation, migration, tube formation and NO production as well as the expression and phosphorylation of eNOS after pretreated with miR-24-3p mimic. Conclusions: HDL can promote angiogenesis by suppressing miR-24-3p expression.

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