Abstract
Microvascular dysfunction accompanied by a dramatic alteration of stable capillary structure is a major hallmark of numerous age-related diseases. In skin, although the role of angiogenesis during dermal reconstitution is well documented, the functional relevance of the extracellular matrix (ECM) stiffness to vascular remodeling and its molecular mechanisms was poorly understood. Here, we developed an ex vivo 3-dimensional angiogenic model using human fat, revealing that “appropriate” stiffness induces vascular maturation associated with upregulated APJ expression, whereas the overexpression of APJ promotes the formation of large vessels even in the absence of the “appropriate” stiffness. Taken together, APJ could be a novel mechanotransducer that accelerates the maturation of cutaneous blood vessels, leading to the prevention of human skin aging.
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References
Discher DE, Janmey P, Wang YL (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310(5751):1139–1143. https://doi.org/10.1126/science.1116995
Kusumbe AP, Ramasamy SK, Adams RH (2014) Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 507(7492):323–328. https://doi.org/10.1038/nature13145
Costea L, Meszaros A, Bauer H, Bauer HC, Traweger A, Wilhelm I, Farkas AE, Krizbai IA (2019) The blood-brain barrier and its intercellular junctions in age-related brain disorders. Int J Mol Sci. https://doi.org/10.3390/ijms20215472
Nakatani M, Fukuda T, Arakawa N, Kawasoe T, Omata S (2013) Softness sensor system for simultaneously measuring the mechanical properties of superficial skin layer and whole skin. Skin Res Technol 19(1):e332-338. https://doi.org/10.1111/j.1600-0846.2012.00648.x
Scimia MC, Hurtado C, Ray S, Metzler S, Wei K, Wang J, Woods CE, Purcell NH, Catalucci D, Akasaka T, Bueno OF, Vlasuk GP, Kaliman P, Bodmer R, Smith LH, Ashley E, Mercola M, Brown JH, Ruiz-Lozano P (2012) APJ acts as a dual receptor in cardiac hypertrophy. Nature 488(7411):394–398. https://doi.org/10.1038/nature11263
Acknowledgements
We thank Suin Kyo and Yoko Umamoto for their technical assistance.
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MS and KK conceived the study and interpreted the results. MS designed and conducted the experiments including histological analyses, SAM and rheological evaluation, ex vivo culture, cell culture, qPCR, western blotting, lentiviral infection, confocal microscopy imaging, quantification and wrote the manuscript. KS provided human tissue samples. YO designed and conducted SAM observation. AN and HO designed and conducted rheological measurements. HK helped to establish the ex vivo culture model. NT guided and advised the research. KK guided the research and wrote the manuscript.
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Sawane, M., Ogura, Y., Nakamura, A. et al. Blood vessels sense dermal stiffness via a novel mechanotransducer, APJ. Angiogenesis 25, 151–154 (2022). https://doi.org/10.1007/s10456-021-09821-6
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DOI: https://doi.org/10.1007/s10456-021-09821-6