Vascular permeability of skeletal muscle microvessels in rat arterial ligation model: in vivo analysis using two-photon laser scanning microscopy
| Autor: | Ayaka Tabuchi, Ryo Ikegami, Rie Shimotsu, Kazuyoshi Yagishita, David C. Poole, Yutaka Kano, Kazuto Masamoto, Tomoyo Asamura, Kzuki Hotta |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Physiology Ischemia Neovascularization Physiologic Vascular permeability 030204 cardiovascular system & hematology Capillary Permeability 03 medical and health sciences 0302 clinical medicine Two-photon excitation microscopy Physiology (medical) medicine Animals Arterial ligation Rats Wistar Muscle Skeletal Ligation Microscopy Confocal Chemistry Microcirculation Skeletal muscle In vivo analysis medicine.disease Arterial occlusion Hindlimb Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Microvessels |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 320:R972-R983 |
| ISSN: | 1522-1490 0363-6119 |
| Popis: | Peripheral artery disease (PAD) in the lower limb compromises oxygen supply due to arterial occlusion. Ischemic skeletal muscle is accompanied by capillary structural deformation. Therefore, using novel microscopy techniques, we tested the hypothesis that endothelial cell swelling temporally and quantitatively corresponds to enhanced microvascular permeability. Hindlimb ischemia was created in male Wistar rat’s by iliac artery ligation (AL). The tibialis anterior (TA) muscle microcirculation was imaged using intravenously infused rhodamine B isothiocyanate dextran fluorescent dye via two-photon laser scanning microscopy (TPLSM) and dye extravasation at 3 and 7 days post-AL quantified to assess microvascular permeability. The TA microvascular endothelial ultrastructure was analyzed by transmission electron microscopy (TEM). Compared with control (0.40 ± 0.15 μm3 × 106), using TPLSM, the volumetrically determined interstitial leakage of fluorescent dye measured at 3 (3.0 ± 0.40 μm3 × 106) and 7 (2.5 ± 0.8 μm3 × 106) days was increased (both P < 0.05). Capillary wall thickness was also elevated at 3 (0.21 ± 0.06 μm) and 7 (0.21 ± 0.08 μm) days versus control (0.11 ± 0.03 μm, both P < 0.05). Capillary endothelial cell swelling was temporally and quantitatively associated with elevated vascular permeability in the AL model of PAD but these changes occurred in the absence of elevations in protein levels of vascular endothelial growth factor (VEGF) its receptor (VEGFR2 which decreased by AL-7 day) or matrix metalloproteinase. The temporal coherence of endothelial cell swelling and increased vascular permeability supports a common upstream mediator. TPLSM, in combination with TEM, provides a sensitive and spatially discrete technique to assess the mechanistic bases for, and efficacy of, therapeutic countermeasures to the pernicious sequelae of compromised peripheral arterial function. |
| Databáze: | OpenAIRE |
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