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  1. Article ; Online: Capillary Dynamics Regulate Post-Ischemic Muscle Damage and Regeneration in Experimental Hindlimb Ischemia.

    Wirth, Galina / Juusola, Greta / Tarvainen, Santeri / Laakkonen, Johanna P / Korpisalo, Petra / Ylä-Herttuala, Seppo

    Cells

    2023  Volume 12, Issue 16

    Abstract: This study aimed to show the significance of capillary function in post-ischemic recovery from the perspective of physiological parameters, such as blood flow, hemoglobin oxygenation and tissue regeneration. Muscle-level microvascular alterations of ... ...

    Abstract This study aimed to show the significance of capillary function in post-ischemic recovery from the perspective of physiological parameters, such as blood flow, hemoglobin oxygenation and tissue regeneration. Muscle-level microvascular alterations of blood flow and hemoglobin oxygenation, and post-ischemic myofiber and capillary responses were analyzed in aged, healthy C57Bl/6J mice (
    MeSH term(s) Animals ; Mice ; Ischemia ; Arteries ; Endothelium, Vascular ; Mice, Inbred C57BL ; Muscles ; Hindlimb
    Language English
    Publishing date 2023-08-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12162060
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Critical limb-threatening ischaemia and microvascular transformation: clinical implications.

    Tarvainen, Santeri / Wirth, Galina / Juusola, Greta / Hautero, Olli / Kalliokoski, Kari / Sjöros, Tanja / Nikulainen, Veikko / Taavitsainen, Jouni / Hytönen, Jarkko / Frimodig, Crister / Happonen, Krista / Selander, Tuomas / Laitinen, Tomi / Hakovirta, Harri H / Knuuti, Juhani / Laham-Karam, Nihay / Hartikainen, Juha / Mäkinen, Kimmo / Ylä-Herttuala, Seppo /
    Korpisalo, Petra

    European heart journal

    2023  Volume 45, Issue 4, Page(s) 255–264

    Abstract: Background and aims: Clinical management of critical limb-threatening ischaemia (CLTI) is focused on prevention and treatment of atherosclerotic arterial occlusions. The role of microvascular pathology in disease progression is still largely unspecified ...

    Abstract Background and aims: Clinical management of critical limb-threatening ischaemia (CLTI) is focused on prevention and treatment of atherosclerotic arterial occlusions. The role of microvascular pathology in disease progression is still largely unspecified and more importantly not utilized for treatment. The aim of this explorative study was to characterize the role of the microvasculature in CLTI pathology.
    Methods: Clinical high-resolution imaging of CLTI patients (n = 50) and muscle samples from amputated CLTI limbs (n = 40) were used to describe microvascular pathology of CLTI at the level of resting muscle blood flow and microvascular structure, respectively. Furthermore, a chronic, low arterial driving pressure-simulating ischaemia model in rabbits (n = 24) was used together with adenoviral vascular endothelial growth factor A gene transfers to study the effect of microvascular alterations on muscle outcome.
    Results: Resting microvascular blood flow was not depleted but displayed decreased capillary transit time (P < .01) in CLTI muscles. Critical limb-threatening ischaemia muscle microvasculature also exhibited capillary enlargement (P < .001) and further arterialization along worsening of myofibre atrophy and detaching of capillaries from myofibres. Furthermore, CLTI-like capillary transformation was shown to worsen calf muscle force production (P < .05) and tissue outcome (P < .01) under chronic ischaemia in rabbits and in healthy, normal rabbit muscle.
    Conclusions: These findings depict a progressive, hypoxia-driven transformation of the microvasculature in CLTI muscles, which pathologically alters blood flow dynamics and aggravates tissue damage under low arterial driving pressure. Hypoxia-driven capillary enlargement can be highly important for CLTI outcomes and should therefore be considered in further development of diagnostics and treatment of CLTI.
    MeSH term(s) Humans ; Rabbits ; Animals ; Peripheral Arterial Disease/therapy ; Risk Factors ; Vascular Endothelial Growth Factor A ; Ischemia ; Hypoxia ; Treatment Outcome ; Retrospective Studies ; Chronic Disease
    Chemical Substances Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2023-08-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 603098-1
    ISSN 1522-9645 ; 0195-668X
    ISSN (online) 1522-9645
    ISSN 0195-668X
    DOI 10.1093/eurheartj/ehad562
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1563: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 640: Show issues

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  3. Article ; Online: T

    Laakso, Hanne / Wirth, Galina / Korpisalo, Petra / Ylä-Herttuala, Elias / Michaeli, Shalom / Ylä-Herttuala, Seppo / Liimatainen, Timo

    NMR in biomedicine

    2018  Volume 31, Issue 5, Page(s) e3909

    Abstract: The identification of areas with regenerative potential in ischemic tissues would allow the targeting of treatments supporting tissue recovery. The regeneration process involves the activation of several cellular and molecular responses which could be ... ...

    Abstract The identification of areas with regenerative potential in ischemic tissues would allow the targeting of treatments supporting tissue recovery. The regeneration process involves the activation of several cellular and molecular responses which could be detected using magnetic resonance imaging (MRI). However, to date, magnetic resonance (MR) relaxation parameters have received little attention in the diagnosis and follow-up of limb ischemia. The purpose of this study was to evaluate the feasibility of different MRI relaxation and diffusion tensor imaging parameters in the detection of areas showing early signs of regeneration in ischemic mouse skeletal muscles. T
    MeSH term(s) Animals ; Diffusion Tensor Imaging ; Female ; Ischemia/diagnostic imaging ; Ischemia/pathology ; Mice ; Muscle, Skeletal/blood supply ; Muscle, Skeletal/diagnostic imaging ; Muscle, Skeletal/pathology ; Regeneration ; Time Factors
    Language English
    Publishing date 2018-03-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1000976-0
    ISSN 1099-1492 ; 0952-3480
    ISSN (online) 1099-1492
    ISSN 0952-3480
    DOI 10.1002/nbm.3909
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2869: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Temporal Dynamics of Gene Expression During Endothelial Cell Differentiation From Human iPS Cells: A Comparison Study of Signalling Factors and Small Molecules.

    Belt, Heini / Koponen, Jonna K / Kekarainen, Tuija / Puttonen, Katja A / Mäkinen, Petri I / Niskanen, Henri / Oja, Joni / Wirth, Galina / Koistinaho, Jari / Kaikkonen, Minna U / Ylä-Herttuala, Seppo

    Frontiers in cardiovascular medicine

    2018  Volume 5, Page(s) 16

    Abstract: Endothelial cell (EC) therapy may promote vascular growth or reendothelization in a variety of disease conditions. However, the production of a cell therapy preparation containing differentiated, dividing cells presenting typical EC phenotype, functional ...

    Abstract Endothelial cell (EC) therapy may promote vascular growth or reendothelization in a variety of disease conditions. However, the production of a cell therapy preparation containing differentiated, dividing cells presenting typical EC phenotype, functional properties and chemokine profile is challenging. We focused on comparative analysis of seven small molecule-mediated differentiation protocols of ECs from human induced pluripotent stem cells. Differentiated cells showed a typical surface antigen pattern of ECs as characterized with flow cytometry analysis, functional properties, such as tube formation and ability to uptake acetylated LDL. Gene expression analysis by RNA sequencing revealed an efficient silencing of pluripotency genes and upregulation of genes related to cellular adhesion during differentiation. In addition, distinct patterns of transcription factor expression were identified during cellular reprogramming providing targets for more effective differentiation protocols in the future. Altogether, our results suggest that the most optimal EC differentiation protocol includes early inhibition of Rho-associated coiled-coil kinase and activation of cyclic AMP signaling, and inhibition of transforming growth factor beta signaling after mesodermal stage. These findings provide the first systematic characterization of the most potent signalling factors and small molecules used to generate ECs from human induced pluripotent stem cells and, consequently, this work improves the existing EC differentiation protocols and opens up new avenues for controlling cell fate for regenerative EC therapy.
    Language English
    Publishing date 2018-03-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2018.00016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: EphrinB2/EphB4 signaling regulates non-sprouting angiogenesis by VEGF.

    Groppa, Elena / Brkic, Sime / Uccelli, Andrea / Wirth, Galina / Korpisalo-Pirinen, Petra / Filippova, Maria / Dasen, Boris / Sacchi, Veronica / Muraro, Manuele Giuseppe / Trani, Marianna / Reginato, Silvia / Gianni-Barrera, Roberto / Ylä-Herttuala, Seppo / Banfi, Andrea

    EMBO reports

    2018  Volume 19, Issue 5

    Abstract: Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, whose best-understood mechanism is sprouting. However, therapeutic VEGF delivery to ischemic muscle induces angiogenesis by the alternative process of intussusception, or ... ...

    Abstract Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, whose best-understood mechanism is sprouting. However, therapeutic VEGF delivery to ischemic muscle induces angiogenesis by the alternative process of intussusception, or vascular splitting, whose molecular regulation is essentially unknown. Here, we identify ephrinB2/EphB4 signaling as a key regulator of intussusceptive angiogenesis and its outcome under therapeutically relevant conditions. EphB4 signaling fine-tunes the degree of endothelial proliferation induced by specific VEGF doses during the initial stage of circumferential enlargement of vessels, thereby limiting their size and subsequently enabling successful splitting into normal capillary networks. Mechanistically, EphB4 neither inhibits VEGF-R2 activation by VEGF nor its internalization, but it modulates VEGF-R2 downstream signaling through phospho-ERK1/2.
    MeSH term(s) Animals ; Cells, Cultured ; Endothelial Cells/metabolism ; Ephrin-B2/metabolism ; Female ; Humans ; Intussusception ; Ischemia/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, SCID ; Muscle, Skeletal/pathology ; Myoblasts/metabolism ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/pathology ; Phosphorylation ; Receptor, EphB4/metabolism ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism
    Chemical Substances Ephrin-B2 ; Vascular Endothelial Growth Factor A ; Receptor, EphB4 (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
    Language English
    Publishing date 2018-04-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.201745054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5433: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 41: Show issues

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