High-Resolution Ultrasound Imaging System for the Evaluation of the Vascular Response to Stent or Balloon Injuries in the Rabbit Iliac Arteries

For novel therapeutic approaches of cardiovascular diseases, the preclinical investigation is of paramount and required appropriate technologies. We investigated the use of high-resolution ultrasound imaging system to evaluate the progression of vascular lesions in a rabbit model. Animals underwent vascular injury using two standard procedures. A bare-metal stent was placed within the left iliac artery, and a balloon injury was induced in the contralateral artery. The animals were kept on a regular diet for 8 weeks. A Vevo3100© VisualSonic high-resolution ultrasound imaging system and the associated software VevoVasc were used for the longitudinal evaluation of the injured arteries and the distal abdominal aorta. The lumen size increased rapidly after the intervention in both iliac arteries. In the balloon-injured artery, the augmentation was transient and significantly reversed, inducing an alteration of the blow flow. In contrast, in the stented segment, the lumen size was maintained enlarged overtime. We demonstrated a significant correlation for the wall thickness and the lumen size between ultrasonic and histological quantification. High-resolution ultrasound imaging in rabbit iliac arteries and the distal abdominal aorta is feasible, reliable and of relevance to investigate novel strategies for the inhibition of hyperplasia induced with standard injury models

Myocardial infarction does not affect circulating haematopoietic stem and progenitor cell self‐renewal ability in a rat model

Given the importance of peripheral blood haematopoietic stem and progenitor cells (HPCs) in post-acute regeneration after acute myocardial infarction (MI), the aim of the present study was to investigate the number and secondary replating capacity/self-renewal ability of HPCs in peripheral blood before and 2 weeks after MI. In female Lewis inbred rats (n = 9), MI was induced by ligation of the left coronary artery, and another nine underwent sham surgery, without ligation, for control purposes. Myocardial infarction was confirmed by troponin I concentrations 24 h after surgery. Peripheral blood was withdrawn and fractional shortening and ejection fraction of the left ventricle were assessed before (day 0) and 14 days after MI or sham surgery (day 14). After mononuclear cell isolation, primary and secondary functional colony-forming unit granulocyte–macrophage (CFU-GM) assays were performed in order to detect the kinetics of functional HPC colony counts and cell self- renewal ability in vitro. The CFU-GM counts and cell self-renewal ability remained unchanged (P < 0.05) in both groups at day 14, without interaction between groups. In the intervention group, higher day 0 CFU-GM counts showed a relationship to lower fractional shortening on day 14 (ρ = −0.82; P < 0.01). Myocardial infarction did not negatively affect circulating HPC self-renewal ability, which suggests a constant regenerative potential in the post-acute phase. A relationship of cardiac contractile function 14 days after MI with circulating CFU-GM counts on day 0 might imply functional colony count as a predictive factor for outcome after infarction

Considering the degradation effects of amino-functional plasma polymer coatings for biomedical application

Materials for biomedical applications typically involve surface engineering. Scaffolds used for tissue engineering, for example, require a surface functionalization in order to support cell growth. The deposition of functional plasma polymer coatings seems to be an attractive approach to modify substrates for biomedical applications.Possible degradation of highly functional plasma polymers and the effect of its degradation products on cell growth, however, are not yet investigated in detail. Plasma polymer formation is governed by gas phase (mainly determining the chemical composition) and surface processes (inducing cross-linking) which both influence the incorporation of amino groups in a-C:H:N coatings deposited by NH₃/C₂H₄ discharges. Aging is studied in air and in aqueous conditions revealing the degradation of such plasma polymers (loss in thickness and loss of amino groups). Degradation products seem to influence viability and proliferation of mouse skeletal muscle cells on electrospun poly(ε-caprolactone) scaffolds. Thus, possible chemical changes as a function of time or exposure to different media must be taken into account in the design of functional plasma polymer coatings for biomedical applications in order to avoid possible adverse effects on cell growth

Myocardial infarction stabilization by cell-based expression of controlled Vascular Endothelial Growth Factor levels

Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)‐based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell‐based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF‐expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS‐ purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia

3D Printing Applied to Tissue Engineered Vascular Grafts

The broad clinical use of synthetic vascular grafts for vascular diseases is limited by their thrombogenicity and low patency rate, especially for vessels with a diameter inferior to 6 mm. Alternatives such as tissue-engineered vascular grafts (TEVGs), have gained increasing interest. Among the different manufacturing approaches, 3D bioprinting presents numerous advantages and enables the fabrication of multi-scale, multi-material, and multicellular tissues with heterogeneous and functional intrinsic structures. Extrusion-, inkjet- and light-based 3D printing techniques have been used for the fabrication of TEVG out of hydrogels, cells, and/or solid polymers. This review discusses the state-of-the-art research on the use of 3D printing for TEVG with a focus on the biomaterials and deposition methods

Economic impacts of a glacial period: a thought experiment to assess the disconnect between econometrics and climate sciences

International audienceAnthropogenic climate change raises growing concerns about its potential catastrophic impacts on both ecosystems and human societies. Yet, several studies on damage induced on the economy by unmitigated global warming have proposed a much less worrying picture of the future, with only a few points of decrease in the world gross domestic product (GDP) per capita by the end of the century, even for a global warming above 4 ∘C. We consider two different empirically estimated functions linking GDP growth or GDP level to temperature at the country level and apply them to a global cooling of 4 ∘C in 2100, corresponding to a return to glacial conditions. We show that the alleged impact on global average GDP per capita runs from −1.8 %, if temperature impacts GDP level, to +36 %, if the impact is rather on GDP growth. These results are then compared to the hypothetical environmental conditions faced by humanity, taking the Last Glacial Maximum as a reference. The modeled impacts on the world GDP appear strongly underestimated given the magnitude of climate and ecological changes recorded for that period. After discussing the weaknesses of the aggregated statistical approach to estimate economic damage, we conclude that, if these functions cannot reasonably be trusted for such a large cooling, they should not be considered to provide relevant information on potential damage in the case of a warming of similar magnitude, as projected in the case of unabated greenhouse gas emissions

Anisotropically oriented electrospun matrices with an imprinted periodic micropattern: a new scaffold for engineered muscle constructs

Engineered muscle constructs provide a promising perspective on the regeneration or substitution of irreversibly damaged skeletal muscle. However, the highly ordered structure of native muscle tissue necessitates special consideration during scaffold development. Multiple approaches to the design of anisotropically structured substrates with grooved micropatterns or parallel-aligned fibres have previously been undertaken. In this study we report the guidance effect of a scaffold that combines both approaches, oriented fibres and a grooved topography. By electrospinning onto a topographically structured collector, matrices of parallel-oriented poly(ε-caprolactone) fibres with an imprinted wavy topography of 90 µm periodicity were produced. Matrices of randomly oriented fibres or parallel-oriented fibres without micropatterns served as controls. As previously shown, un-patterned, parallel-oriented substrates induced myotube orientation that is parallel to fibre direction. Interestingly, pattern addition induced an orientation of myotubes at an angle of 24° (statistical median) relative to fibre orientation. Myotube length was significantly increased on aligned micropatterned substrates in comparison to that on aligned substrates without pattern (436 ± 245 µm versus 365 ± 212 µm; p < 0.05). We report an innovative, yet simple, design to produce micropatterned electrospun scaffolds that induce an unexpected myotube orientation and an increase in myotube length

Activation of the erythropoietin system in exhaustively exercise muscle relates to ACE gene polymorphism-modulated metabolic signalling and mitochondrial transcript expression

Introduction Introduction A fall in muscle oxygen saturation is a potent activator of mitochondrial biogenesis in exercised skeletal muscle which is subject to the training-modulated influence of the insertion/deletion polymorphism of the angiotensin converting enzyme gene (ACE-I/D; Gasser et al 2022) and may involve paracrine erythropoietin (EPO) signaling (Desplanches et al 2014, Nijholt et al 2021). We tested the hypothesis that erythropoietin expression and signaling in fatiguingly exercised muscle would correspond to the expression of hypoxia-regulated mitochondrial genes and altered metabolic signaling and would be subject to a genetic influence by ACE-I/D. Methods Methods 22 healthy, male white Caucasian men (27.0 +/- 1.4 years; BMI 23.6 +/- 0.6 kg m-2) completed a session of fatiguing one-legged exercise in the fasted state. Microbiopsies were collected from m. vastus lateralis of the non-exercised leg immediately before exercise, and ½, 3, and 8 hours thereafter from the exercising leg. Levels of the hypoxia-regulated cytochrome c oxidase subunit 4 isoforms 1 and 2 (COX4I1 and COX4I2), ACE and EPO transcript, glycogen concentration in m. vastus lateralis, the ACE-I/D genotype and aerobic fitness state were assessed as described (Desplanches et al 2014; Gasser et al 2022). EPO protein concentration and phosphorylation of intracellular transducers of EPO signaling were quantified in muscle homogenates with validated enzyme-linked immune sorbent and a phospho-kinase assays. Effects and Pearson correlations were assessed with analysis of variance and declared significant at p &lt; 0.05. Results One-legged exercise produced metabolic fatigue as indicated by the voluntary cessation of exercise and a reduced glycogen concentration in m. vastus lateralis in all subjects ½ hour after exercise (-0.044 mg mg-1). Concomitantly, EPO protein levels were 4-fold lowered; and subsequently increased 3-8 hours after cessation of exercise alike EPO transcripts levels. Aerobically fit ACE I-allele carriers demonstrated a sparing of muscle glycogen, exaggerated EPO transcript response, and higher phosphorylation levels of EPO signal transducers [STAT5a-Y694 (+31%), STAT5b-Y699 (+40%)]. The phosphorylation level of the metabolic signal transducer AMPKa2-T172 correlated to EPO transcript levels 3 hours post exercise (r = 0.61). EPO protein levels correlated to ACE and COX4I2 transcript levels (r = -0.79; -0.54). Discussion The findings highlight that a paracrine loop of metabolically-regulated EPO signaling exists in exercised human skeletal muscle which variability is associated with the ACE-I/D gene polymorphism in fair correspondence with a mitochondrial marker of local hypoxia. References Desplanches, D., Amami, M., Mueller, M., Hoppeler, H., Kreis, R., &amp; Flück, M. (2014). Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work. European Journal of Applied Physiology, 114, 405-417. https://doi.org/10.1007/s00421-013-2783-8 Gasser, B., Franchi, M. V., Ruoss, S., Frei, A., Popp, W. L., Niederseer, D., Catuogno, S., Frey, W. O., &amp; Flück, M. (2022). Accelerated muscle deoxygenation in aerobically fit subjects during exhaustive exercise is associated with the ACE insertion allele. Frontiers in Sports and Active Living, 4, Article 814975. https://doi.org/10.3389/fspor.2022.814975 Nijholt, K. T., Meems, L. M. G., Ruifrok, W. P. T., Maass, A. H., Yurista, S. R., Pavez-Giani, M. G., Mahmoud, B., Wolters, A. H. G., van Veldhuisen, D. J., van Gilst, W. H., Silljé, H. H. W., de Boer, R. A., &amp; Westenbrink, B. D. (2021). The erythropoietin receptor expressed in skeletal muscle is essential for mitochondrial biogenesis and physiological exercise. Pflügers Archiv - European Journal of Physiology, 473, 1301-1313. https://doi.org/10.1007/s00424-021-02577-