Browsing by Subject "NEOVASCULARIZATION"

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  • Theelen, Thomas L.; Lappalainen, Jari P.; Sluimer, Judith C.; Gurzeler, Erika; Cleutjens, Jack P.; Gijbels, Marion J.; Biessen, Erik A. L.; Daemen, Mat J. A. P.; Alitalo, Kari; Yla-Herttuala, Seppo (2015)
    Objective: Angiopoietin-2 (Ang-2) blocking agents are currently undergoing clinical trials for use in cancer treatment. Ang-2 has also been associated with rupture-prone atherosclerotic plaques in humans, suggesting a role for Ang-2 in plaque stability. Despite the availability of Ang-2 blocking agents, their clinical use is still lacking. Our aim was to establish if Ang-2 has a role in atheroma development and in the transition of subclinical to clinically relevant atherosclerosis. We investigated the effect of antibody-mediated Ang-2 blockage on atherogenesis after in a mouse model of atherosclerosis. Methods: Hypercholesterolemic (low-density lipoprotein receptor(-/-) apolipoprotein B-100/100) mice were subjected to high-cholesterol diet for eight weeks, one group with and one group without Ang-2 blocking antibody treatment during weeks 4-8. To enhance plaque development, a peri-adventitial collar was placed around the carotid arteries at the start of antibody treatment. Aortic root, carotid arteries and brachiocephalic arteries were analyzed to evaluate the effect of Ang-2 blockage on atherosclerotic plaque size and stable plaque characteristics. Results: Anti-Ang-2 treatment reduced the size of fatty streaks in the brachiocephalic artery (-72%, p <0.05). In addition, antibody-mediated Ang-2 blockage reduced plasma triglycerides (-27%, p <0.05). In contrast, Ang-2 blockage did not have any effect on the size or composition (collagen content, macrophage percentage, adventitial microvessel density) of pre-existing plaques in the aortic root or collar-induced plaques in the carotid artery. Conclusions: Ang-2 blockage was beneficial as it decreased fatty streak formation and plasma triglyceride levels, but had no adverse effect on pre-existing atherosclerosis in hypercholesterolemic mice. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.
  • Grunewald, M.; Kumar, S.; Sharife, H.; Volinsky, E.; Gileles-Hillel, A.; Licht, T.; Permyakova, A.; Hinden, L.; Azar, S.; Friedmann, Y.; Kupetz, P.; Tzuberi, R.; Anisimov, A.; Alitalo, K.; Horwitz, M.; Leebhoff, S.; Khoma, O. Z.; Hlushchuk, R.; Djonov, Valentin G; Abramovitch, R.; Tam, J.; Keshet, E. (2021)
    Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life span. Healthier aging was evidenced by favorable metabolism and body composition and amelioration of aging-associated pathologies including hepatic steatosis, sarcopenia, osteoporosis, "inflammaging" (age-related multiorgan chronic inflammation), and increased tumor burden. These results indicate that VEGF signaling insufficiency affects organ aging in mice and suggest that modulating this pathway may result in increased mammalian life span and improved overall health.
  • Segersvard, Heli; Lakkisto, Paivi; Forsten, Hanna; Immonen, Katariina; Kosonen, Riikka; Palojoki, Eeva; Kankuri, Esko; Harjula, Ari; Laine, Mika; Tikkanen, Ilkka (2015)
  • Friedmann, Andrea; Goehre , Felix; Ludtka, Christopher; Mendel, Thomas; Meisel, Hans-Joerg; Heilmann, Andreas; Schwan, Stefan (2017)
    Degeneration of intervertebral disc (IVD) tissue is characterized by several structural changes that result in variations in disc physiology and loss of biomechanical function. The complex process of degeneration exhibits highly intercorrelated biomechanical, biochemical, and cellular interactions. There is currently some understanding of the cellular changes in degenerated intervertebral disc tissue, but microstructural changes and deterioration of the tissue matrix has previously been rarely explored. In this work, sequestered IVD tissue was successfully characterized using histology, light microscopy, and scanning electron microscopy (SEM) to quantitatively evaluate parameters of interest for intervertebral disc degeneration (IDD) such as delamination of the collagenous matrix, cell density, cell size, and extra cellular matrix (ECM) thickness. Additional qualitative parameters investigated included matrix fibration and irregularity, neovascularization of the IVD, granular inclusions in the matrix, and cell cluster formation. The results of this study corroborated several previously published findings, including those positively correlating female gender and IVD cell density, age and cell size, and female gender and ECM thickness. Additionally, an array of quantitative and qualitative investigations of IVD degeneration could be successfully evaluated using the given methodology, resin-embedded SEM in particular. SEM is especially practical for studying micromorphological changes in tissue, as other microscopy methods can cause artificial tissue damage due to the preparation method. Investigation of the microstructural changes occurring in degenerated tissue provides a greater understanding of the complex process of disc degeneration as a whole. Developing a more complete picture of the degenerative changes taking place in the intervertebral disc is crucial for the advancement and application of regenerative therapies based on the pathology of intervertebral disc degeneration. (C) 2016 Elsevier Ltd. All rights reserved.