Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system

2008 ◽  
Vol 294 (3) ◽  
pp. R811-R818 ◽  
Author(s):  
Chao-Hung Wang ◽  
Wen-Jin Cherng ◽  
Ning-I Yang ◽  
Chia-Ming Hsu ◽  
Chi-Hsiao Yeh ◽  
...  
Keyword(s):  
Critical Role ◽  
Serum Levels ◽  
Blood Levels ◽  
Short Term ◽  
Endothelial Progenitor ◽  
Beneficial Effects ◽  
Dpp Iv ◽  
Before And After ◽  
Cell Mobilization

Cyclosporin A (CsA) improves the success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57BL/6 mice were divided into control and CsA-treated groups. Before and after hindlimb ischemia was induced, circulating EPC number and serum levels of different cytokines were measured. Compared with the controls, CsA treatment significantly increased the blood levels of stroma-derived factor-1α and stem cell factor after ischemic stress ( P < 0.001). The CsA group displayed a significant increase in the number of circulating EPCs (sca-1+KDR+ and c-kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the numbers of EPCs incorporated into the Matrigel and ischemic limbs ( P < 0.05). In the peripheral blood, CsA significantly decreased CD26+ cell numbers and attenuated the plasma CD26/DPP IV activity ( P < 0.001). Furthermore, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In summary, CsA manipulates the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.

Abstract 228: Short-term Cyclosporine Therapy Increases Ischemia-induced Endothelial Progenitor Cell Mobilization Through Manipulation Of The CD26 System

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Chao Hung Wang ◽  
Wen-Jin Cherng ◽  
I-Chang Hsieh ◽  
Ning-I Yang ◽  
Chi-Hsiao Yeh
Keyword(s):  
Bone Marrow ◽  
Critical Role ◽  
Fold Increase ◽  
Serum Levels ◽  
Short Term ◽  
Endothelial Progenitor ◽  
Beneficial Effects ◽  
Dpp Iv

Cyclosporine A (CsA), an immunosuppressant, has remarkably improved the short-term success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57 BL/6 mice were divided into control and CsA-treated groups. Circulating EPCs were enumerated before and after hindlimb ischemia was induced. Levels of stroma-derived factor-1α (SDF-1α), stem cell factor (SCF), vascular endothelial grow factor (VEGF), and granulocyte-colony stimulating factor (G-CSF) were measured in the blood. Compared to the controls, CsA treatment significantly increased the serum levels of SDF-1α and SCF (p < 0.001), but not of VEGF or G-CSF after ischemic stress. The CsA group displayed a significant increase in the number of circulating EPCs (with a 7-fold increase in sca-1 + KDR + cells and a 1.5-fold increase in c-kit + CD31 + cells versus the controls at 18 h after ischemia was induced, both p < 0.05). In vivo , CsA also caused 2- and 5-fold increases in the numbers of bone marrow-derived EPCs incorporated into the Matrigel and ischemic limbs, respectively (p < 0.05). In the peripheral blood, CsA significantly decreased CD26 + cell numbers (p < 0.001) and attenuated the plasma CD26/DPP IV activity (p < 0.001). CsA did not alter the acitivty of MMP-2 or MMP-9 in vitro or in vivo . Compared to the controls, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In conclusions, this study demonstrated that CsA manipulates the mobilization of bone marrow-derived EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogensis of ischemic tissues.

Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1340-1346 ◽  
Author(s):  
Christopher Heeschen ◽  
Alexandra Aicher ◽  
Ralf Lehmann ◽  
Stephan Fichtlscherer ◽  
Mariuca Vasa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Heart Disease ◽  
Progenitor Cells ◽  
Serum Levels ◽  
Endothelial Progenitor ◽  
In Vivo Models ◽  
Stem And Progenitor Cells ◽  
Cell Mobilization ◽  
And Function

Abstract Increasing evidence suggests that postnatal neovascularization involves the recruitment of circulating endothelial progenitor cells (EPCs). Hematopoietic and endothelial cell lineages share common progenitors. Cytokines formerly thought to be specific for the hematopoietic system have only recently been shown to affect several functions in endothelial cells. Accordingly, we investigated the stimulatory potential of erythropoietin (Epo) on EPC mobilization and neovascularization. The bone marrow of Epo-treated mice showed a significant increase in number and proliferation of stem and progenitor cells as well as in colony-forming units. The number of isolated EPCs and CD34+/flk-1+ precursor cells was significantly increased in spleen and peripheral blood of Epo-treated mice compared with phosphate-buffered saline–treated mice. In in vivo models of postnatal neovascularization, Epo significantly increased inflammation- and ischemia-induced neovascularization. The physiologic relevance of these findings was investigated in patients with coronary heart disease. In a multivariate regression model, serum levels of Epo and vascular endothelial growth factor were significantly associated with the number of stem and progenitor cells in the bone marrow as well as with the number and function of circulating EPCs. In conclusion, the present study suggests that Epo stimulates postnatal neovascularization at least in part by enhancing EPC mobilization from the bone marrow. Epo appears to physiologically regulate EPC mobilization in patients with ischemic heart disease. Thus, Epo serum levels may help in identifying patients with impaired EPC recruitment capacity.

scholarly journals FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dezhong Wang ◽  
Yuan Yin ◽  
Shuyi Wang ◽  
Tianyang Zhao ◽  
Fanghua Gong ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Metabolic Regulation ◽  
Cardiac Injury ◽  
Serum Levels ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cardiac Tissues ◽  
Beneficial Effects

AbstractAs a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats

2014 ◽  
Vol 307 (5) ◽  
pp. E447-E455 ◽  
Author(s):  
Lorenzo Glorie ◽  
Geert J. Behets ◽  
Lesley Baerts ◽  
Ingrid De Meester ◽  
Patrick C. D'Haese ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Strength ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Bending Test ◽  
Control Group ◽  
Mechanical Resistance ◽  
Three Point Bending ◽  
Dpp Iv

Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups ( n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management.

scholarly journals Effect of 12 Months of Exercise with Stachys Lavandulifolia Consumption on anxiety, Metabolic Syndrome Profiles and Antioxidant Defense and Lipid Peroxidation in Women with Syndrome Metabolic

2020 ◽  
Author(s):  
Ali osali ◽  
Alireza Rostami
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Peroxidation ◽  
Aerobic Exercise ◽  
Antioxidant Defense ◽  
Training Group ◽  
Serum Levels ◽  
Control Group ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Before And After

Abstract BackgroundThe purpose of this study was to investigate the effect of 12 months of aerobic exercise combining stachys lavandulifolia (S. lavandulifolia) consumption on anxiety, Metabolic Syndrome profiles and antioxidant defense (Glutathione) and lipid peroxidation (Malondialdehyde) in 50-65 years old women with syndrome metabolic.Methods48 women with syndrome Metabolic were randomly divided into four groups: exercise (n=12), exercise+S. lavandulifolia (n=12), S. lavandulifolia (n=12) and control group (n=12). S. lavandulifolia groups consumed 3 g aerial parts of S. lavandulifolia daily. Training groups performed an exercise protocol of aerobic exercise for 12 months (three sessions per week). Blood samples were obtained before and after training period for antioxidant indicators and lipid degradation measurement. Also, Beck anxiety questionnaire used for evaluating levels of anxiety. T-test and one-way analysis of variance were used for the evaluation of within-group and between-group differences, respectively.ResultsA significant increase was observed in serum levels of Malondialdehyde (P =0.004), Catalase indexes (Pvalue= 0.01), and Glutathione (P=0.001) in the training group and S. lavandulifolia groups after 12 months. Body weight, BMI, and SBP and Anexiety was decreased significantly greater in exercise +S. lavandulifolia group compared to control, exercise and S. lavandulifolia groups (P=0.001)ConclusionAnxiolytic effect and Anti-Oxidative Stress Activity was seen, so taking S. lavandulifolia along with exercises may have beneficial effects on reinforcement the antioxidant system and prevention of anxiety and The negative effects of indicators related to cardiovascular disease in women with metabolic syndrome.

scholarly journals Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia

2021 ◽  
Vol 22 (24) ◽  
pp. 13609
Author(s):  
Lucas Wauters ◽  
Raúl Y. Tito ◽  
Matthias Ceulemans ◽  
Maarten Lambaerts ◽  
Alison Accarie ◽  
...  
Keyword(s):  
Functional Dyspepsia ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Potential Role ◽  
Short Term ◽  
Beneficial Effects ◽  
Rrna Sequencing ◽  
Before And After

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.

scholarly journals A novel Axin2 knock-in mouse model for visualization and lineage tracing of WNT/CTNNB1 responsive cells

2020 ◽  
Author(s):  
Anoeska Agatha Alida van de Moosdijk ◽  
Yorick Bernardus Cornelis van de Grift ◽  
Saskia Madelon Ada de Man ◽  
Amber Lisanne Zeeman ◽  
Renée van Amerongen
Keyword(s):  
Cell Fate ◽  
Mouse Strain ◽  
Critical Role ◽  
Lineage Tracing ◽  
Fluorescent Reporter ◽  
Cell Fate Decisions ◽  
Stem Cell Maintenance ◽  
Signaling Dynamics ◽  
Before And After

AbstractWnt signal transduction controls tissue morphogenesis, maintenance and regeneration in all multicellular animals. In mammals, the WNT/CTNNB1 (Wnt/β-catenin) pathway controls cell proliferation and cell fate decisions before and after birth. It plays a critical role at multiple stages of embryonic development, but also governs stem cell maintenance and homeostasis in adult tissues. However, it remains challenging to monitor endogenous WNT/CTNNB1 signaling dynamics in vivo. Here we report the generation and characterization of a new knock-in mouse strain that doubles as a fluorescent reporter and lineage tracing driver for WNT/CTNNB1 responsive cells. We introduced a multi-cistronic targeting cassette at the 3’ end of the universal WNT/CTNNB1 target gene Axin2. The resulting knock-in allele expresses a bright fluorescent reporter (3xNLS-SGFP2) and a doxycycline-inducible driver for lineage tracing (rtTA3). We show that the Axin2P2A-rtTA3-T2A-3xNLS-SGFP2 strain labels WNT/CTNNB1 cells at multiple anatomical sites during different stages of embryonic and postnatal development. It faithfully reports the subtle and dynamic changes in physiological WNT/CTNNB1 signaling activity that occur in vivo. We expect this mouse strain to be a useful resource for biologists who want to track and trace the location and developmental fate of WNT/CTNNB1 responsive stem cells in different contexts.Abstract Figure

Direct effect of physiological doses of arginine vasopressin on the arterial wall in vivo

1978 ◽  
Vol 234 (2) ◽  
pp. H167-H172 ◽  
Author(s):  
E. Monos ◽  
R. H. Cox ◽  
L. H. Peterson
Keyword(s):  
Arginine Vasopressin ◽  
Flow Resistance ◽  
Arterial Wall ◽  
External Diameter ◽  
Short Term ◽  
Before And After ◽  
Circulatory Control ◽  
Anesthetized Dogs ◽  
Vascular Beds

Effects of topically applied arginine vasopressin (VPA), in 100-150 muU/ml blood concentration, on external diameter (D) and on dynamic elastic modulus (E*) of surgically denervated common carotid (CC) and femoral (FA) arteries have been studied before and after hypophysectomy in anesthetized dogs. Changes in D, E*, and flow resistance (R) of the CC and FA vascular beds before and after removal of the pituitary were also determined. It was found that VPA elicited a substantial (max 21-26%) decrease in E* and a smaller (max 5.9-6.9%) reduction in D of FA independent of the presence of absence of the pituitary gland. The VPA effect developed more rapidly after hypophysectomy than before. In the CC, VPA did not significantly affect values of E*. During the 1-h period after hypophysectomy, statistically significant decreases in E*-CC, E*-FA, and D-CC were observed, but D-FA did not change, although arterial pressure as well as R-FA and R-CC were diminished. These results give further support to physiological vascular actions of VPA and a possible role in short-term circulatory control. In large arteries, the effects of VPA also seem to be regionally differentiated.

In vivo perspective study about the effects of weekly low dose administration of zoledronic acid (ZA) on angiogenesis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3558-3558
Author(s):  
D. Santini ◽  
B. Vincenzi ◽  
F. Battistoni ◽  
S. Galluzzo ◽  
L. Rocci ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Cancer Patients ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Low Doses ◽  
Dose Administration ◽  
Before And After ◽  
Endothelial Growth Factor ◽  
First Time

3558 Purpose: Recent data have demonstrated in preclinical tumor models an antiangiogenic and antitumor activity of low weekly doses of ZA. As a consequence, the purpose of this study was to confirm these data, evaluating in cancer patients the modifications in angiogenic cytokines levels following repeated weekly low doses of ZA. Experimental Design: 26 consecutive cancer patients with bone metastases treated, for the first time, with four weekly doses of 1 mg of ZA followed by standard doses (4 mg every 28 days) were prospectively evaluated for circulating levels of vascular endothelial growth factor (VEGF) at different time points: just before and after 1, 7, 14, 21, 28, 56 and 84 days following the first disphosphonate infusion. Results: Basal serum VEGF median levels were significantly decreased just after 7 days (-29.7%) (with only one weekly infusion) (P=0.038), This significant decrease of circulating VEGF levels persisted 14(-33.2%), 21 (-39.4%), 28(-31.8%), 56(-33.6%) and 84(-27.9%) days after the first infusion (respectively, P=0.002, P=0.001, P=0.008, P=0.002, P=0.014). Conclusions: This study confirms, for the first time in humans, that weekly low doses of zoledronic acid could have antiangiogenic properties through a significant and long lasting decrease of VEGF serum levels. No significant financial relationships to disclose.

scholarly journals Effects of Wine and Tyrosol on the Lipid Metabolic Profile of Subjects at Risk of Cardiovascular Disease: Potential Cardioprotective Role of Ceramides

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1679
Author(s):  
Jose Rodríguez-Morató ◽  
Anna Boronat ◽  
Gabriele Serreli ◽  
Laura Enríquez ◽  
Alex Gomez-Gomez ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Function ◽  
Blood Lipid ◽  
White Wine ◽  
Cvd Risk ◽  
Blood Lipid Profile ◽  
Beneficial Effects ◽  
Before And After ◽  
Risk Biomarkers

Ceramides are a class of sphingolipids which have recently been shown to be better cardiovascular disease (CVD) risk predictors than traditional CVD risk biomarkers. Tyrosol (TYR) is a dietary phenolic compound known to possess cardioprotective effects per se or through its in vivo active metabolite hydroxytyrosol. The purpose of this study was to evaluate the effects of the co-administration of white wine (WW) and TYR on circulating levels of ceramides and other lipids in humans at high CVD risk. Volunteers underwent a randomized controlled crossover clinical trial (4-week duration per intervention) with three different interventions: control, WW, and WW enriched with a capsule of TYR (WW + TYR). Endothelial function cardiovascular biomarkers and plasma lipidomic profile were assessed before and after each intervention. It was found that the WW + TYR intervention resulted in lower levels of three ceramide ratios, associated with an improvement of endothelial function (Cer C16:0/Cer C24:0, Cer C18:0/Cer C24:0, and Cer C24:1/Cer C24:0), when compared to the control intervention. Moreover, WW + TYR was able to minimize the alterations in plasma diacylglycerols concentrations observed following WW. Overall, the results obtained show that the antioxidant TYR administered with WW exerts beneficial effects at the cardiovascular level, in part by modulating blood lipid profile.

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