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Copper (Cu) deficiency plays an important role in the development of cardiovascular disorders. Resveratrol (RSV) possesses pleiotropic cardiovascular benefits; however, the mechanism(s) by which RSV exerts protective effects are not completely understood. Male Wistar rats at 6 weeks of age were fed for 8 weeks with a Cu deficient diet (no added Cu, Cu = 0). In addition, Cu deficient rats were supplemented with RSV (500 mg/kg of diet, n = 9). Blood and intestinal samples were taken for further analysis together with internal organs and thoracic arteries. RSV supplementation resulted in elevated blood plasma levels of Cu (x2.1) and Zn (x1.1), in an increased activity of superoxide dismutase (SOD, x1.5) and ferric reducing antioxidant power (FRAP, x1.2). Meanwhile, markers of lipid peroxidation expressed as malondialdehyde (MDA, x1.5) and lipid hydroperoxides (LOOH, x1.1) were also increased in a significant way. Food intake, body weight, blood glucose, catalase, ceruloplasmin, lipid profile and intestinal samples were not modified. RSV enhanced the vasoconstriction of isolated thoracic arteries to noradrenaline (x1.4), potentiated the vasodilation to acetylcholine (ACh, x1.4) and increased the sensitivity to sodium nitroprusside (SNP). In addition, preincubation with the cyclooxygenase (COX)-inhibitor, indomethacin, potentiated the ACh-induced vasodilation, which was more pronounced in animals not supplemented with RSV. The K ATP channel opener, pinacidil, induced a similar response in both studied groups. In conclusion, this study demonstrates that RSV supplementation influences oxidative stress and the antioxidant status, which may modify the vascular response in Cu deficiency., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

We aimed to study the physiological effects of diet supplemented with copper (Cu) nanoparticles (NPs). During the eight weeks of the experiment, young Wistar rats (at seven weeks of age, n = 9) were supplemented with 6.5 mg of Cu either as NPs or carbonate salt (Cu6.5). A diet that was not supplemented with Cu served as a negative control (Cu0). The impact of nano Cu supplementation on lipid (reflected as thiobarbituric acid reactive substances-TBARS) and protein peroxidation (thiol and carbonyl groups) in blood plasma as well as the influence on the vasodilatory mechanism(s) of isolated rat thoracic arteries were studied. Supplementation with Cu enhanced lipid peroxidation (TBARS) in NP6.5 (x2.4) and in Cu6.5 (x1.9) compared to the negative control. Significant increase in TBARS was also observed in NP6.5 (x1.3) compared to the Cu6.5 group. The level of thiol groups increased in NP6.5 (x1.6) compared to Cu6.5. Meanwhile, significant (x0.6) decrease was observed in the Cu6.5 group compared to the negative control. Another marker of protein oxidation, carbonyl groups increased in NP6.5 (x1.4) and Cu6.5 (x2.3) compared to the negative control. However significant difference (x0.6) was observed between NP6.5 and Cu6.5. Arteries from Cu supplemented rats exhibited an enhanced vasodilation to gasotransmitters: nitric oxide (NO) and carbon monoxide (CO). An enhanced vasodilation to NO was reflected in the increased response to acetylcholine (ACh) and calcium ionophore A23187. The observed responses to ACh and CO releasing molecule (CORM-2) were more pronounced in NP6.5. The activator of cGMP-dependent protein kinases (8-bromo-cGMP) induced similar vasodilation of thoracic arteries in NP6.5 and Cu0 groups, while an increased response was observed in the Cu6.5 group. Preincubation with the inducible nitric oxide (iNOS) synthase inhibitor- 1400W, decreased the ACh-induced vasodilation in NP6.5, exclusively. Meanwhile the eicosanoid metabolite of arachidonic acid (20-HETE) synthesis inhibitor-HET0016, enhanced vasodilation of arteries from Cu0 group. In conclusion, this study demonstrates that supplementation with nano Cu influences oxidative stress, which further has modified the vascular response., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Impaired endothelium-dependent relaxation (EDR) is a hallmark of endothelial dysfunction. A deficiency of tetrahydrobiopterin (BH 4 ) causes endothelial NOS to produce ROS rather than NO. PPARδ is an emerging target for pharmacological intervention of endothelial dysfunction. Thus, the present study examined the role of PPARδ in the regulation of dihydrofolate reductase (DHFR), a key enzyme in the BH 4 salvage pathway., Experimental Approach: Gene expression was measured by using qRT-PCR and western blotting. Biopterins and ROS were determined by using HPLC. NO was measured with fluorescent dye and electron paramagnetic resonance spectroscopy. Vasorelaxation was measured by Multi Myograph System., Key Results: The PPARδ agonist GW501516 increased DHFR and BH 4 levels in endothelial cells (ECs). The effect was blocked by PPARδ antagonist GSK0660. Chromatin immunoprecipitation identified PPAR-responsive elements within the 5'-flanking region of the human DHFR gene. The promoter activity was examined with luciferase assays using deletion reporters. Importantly, DHFR expression was suppressed by palmitic acid (PA, a saturated fatty acid) but increased by docosahexaenoic acid (DHA, a polyunsaturated fatty acid). GSK0660 prevented DHA-induced increased DHFR expression. Conversely, the suppressive effect of PA was mitigated by GW501516. In mouse aortae, GW501516 ameliorated the PA-impaired EDR. However, this vasoprotective effect was attenuated by DHFR siRNA or methotrexate. In EC-specific Ppard knockout mice, GW501516 failed to improve vasorelaxation., Conclusion and Implications: PPARδ prevented endothelial dysfunction by increasing DHFR and activating the BH 4 salvage pathway. These results provide a novel mechanism for the protective roles of PPARδ against vascular diseases., (© 2019 The British Pharmacological Society.)

In this study, we aimed at performing a histomorphometric analysis of human left internal thoracic artery (ITA) samples as well as at correlating the histomorphometric findings with the clinical profile, including risk factors and medication. Distal segments of ITA were obtained from 54 patients undergoing coronary artery bypass grafting. Histological observation was performed in paraffin-embedded transverse sections of ITA through four staining protocols: hematoxylin-eosin, van Gieson, Masson's trichrome and von Kossa. Morphometric analysis included the intimal width (IW), medial width (MW) and intima/media ratio (IMR). No overt atherosclerotic lesions were observed. Mild calcifications were observed across the vascular wall layers in almost all samples. Multivariable linear regression analysis showed associations between IW and IMR and the following clinical variables: age, gender, kidney function expressed as eGFR and myocardial infarction history. Age (odds ratio = 1.16, P = 0.004), female gender (odds ratio = 11.34, P = 0.011), eGFR (odds ratio = 1.03, P = 0.059) and myocardial infarction history (odds ratio = 4.81, P = 0.040) were identified as the main clinical predictors for intimal hyperplasia. Preatherosclerotic lesions in ITA samples from patients undergoing coronary revascularization were associated not only with classical cardiovascular risk factors such as age and gender, but also with other clinical variables, namely kidney function and myocardial infarction history., Competing Interests: The authors have declared that no competing interests exist.

Reported here are the results of an experimental study on the response to low-intensity cavitation induced by low-frequency (4-6 W/cm 2 , 20 kHz and 32.6 kHz) ultrasound of isolated human arterial samples taken during conventional myocardial revascularization operations. Studies have found that low-frequency ultrasound results in a significant (48%-54%) increase in isometric contraction force and does not depend on the number of exposures (10 or 20) or the time passed since the start of ultrasound (0, 10 and 20 min), but does depend on the frequency and location (internal or external) of the blood vessels for the application of ultrasound. Diltiazem (an inhibitor of slow calcium channels) and carbachol (an agonist of muscarinic receptors) used in a concentration-dependent manner did not modify the relaxation dynamics of smooth muscle affected by ultrasound. Thus, ultrasound conditioned to the augmentation of the isometric contraction force the smooth muscle of blood vessels and did not improve endothelial- and calcium channel blocker-dependent relaxation., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The body plan of arthropods and vertebrates involves the formation of repetitive segments, which subsequently diversify to give rise to different body parts along the antero-posterior/rostro-caudal body axis. Anatomical variations between body segments are crucial for organ function and organismal fitness. Pioneering work in Drosophila has established that Hox transcription factors play key roles both in endowing initially identical segments with distinct identities and organogenesis. The focus of this review is on Alary Muscles (AMs) and the newly discovered Thoracic Alary-Related Muscles (TARMs). AMs and TARMs are thin muscles which together connect the circulatory system and different midgut regions to the exoskeleton, while intertwining with the respiratory tubular network. They were hypothesized to represent a new type of muscles with spring-like properties, maintaining internal organs in proper anatomical positions during larval locomotion. Both the morphology of TARMs relative to AMs, and morphogenesis of connected tissues is under Hox control, emphasizing the key role of Hox proteins in coordinating the anatomical development of the larva., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the distribution of superparamagnetic iron oxide (SPIO)-labeled cells in a perfused segment of a porcine artery and to estimate the number of adherent cells by means of magnetic resonance (MR) imaging., Materials and Methods: Six vessel specimens (diameters between 0.8 and 1.2 cm) were placed in a bioreactor system, and 2 × 10(4) to 1 × 10(6) SPIO-labeled endothelial colony-forming cells were injected into the artery within the perfused reactor. The area of resulting signal extinctions at the inner wall of the vessels was quantified on MR images by using a high-resolution T2*-weighted sequence with a slice-by-slice approach. After imaging, the labeled cells were quantified histologically., Results: The total iron load of each cell was 56.5 pg ± 14.4. In the applied range of 2 × 10(4) to 1 × 10(6) cells per vessel, the area of iron-induced signal extinction at the vessel wall on T2*-weighted imaging corresponded to the histologically detected cell number (r = 0.98, P < .001)., Conclusions: A correlation between the area of signal extinction and the number of labeled cells at the vessel wall was found. This might help to evaluate dose rates in further clinical applications of intravascular cell-based therapies., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

Introduction: Indications for flow-through latissimus dorsi (LD) flaps have been limited for reconstructing distal extremities. In addition, there has been little discussion in regard to the question of which branch is most suitable as a distal runoff of the flow-through anastomosis. The aims of this study were to investigate the feasibility of flow-through LD flaps in various areas in the body and the rationale for branch selection for the distal runoff vessel., Methods: This retrospective study included 33 patients who underwent reconstruction of an oncology-related defect with a free flow-through LD flap. Defect locations, branches used for the distal runoff, and postoperative complications were investigated., Results: The defect location was in the lower extremity in 13 patients, the scalp in seven, the upper extremity in six, the pelvis in six, and the chest in one. In 19 of the 33 patients, the defects were located in areas other than the distal extremities. The circumflex scapular artery (CSA) was most frequently used as the distal runoff vessel (24 patients) followed by the serratus anterior branch (SAB) (five patients). All flaps were transferred successfully without anastomotic failure., Conclusions: The flow-through LD flap is a reliable option for reconstruction in many areas of the body. It can provide high success rates not only for extremity reconstruction but also for scalp and pelvic reconstruction. The CSA matches well with the workhorse recipient vessels. The SAB is suitable when there is a vascular defect of the recipient artery., (Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)