Penile cavernous sinusoids are Prox1-positive hybrid vessels
Endothelial cells (ECs) of blood and lymphatic vessels have distinct identity markers that define their specialized functions. Recently, hybrid vasculatures with both blood and lymphatic vessel-specific features have been discovered in multiple tissues. Here, we identify the penile cavernous sinusoi...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2024-01-01
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| Series: | Vascular Biology |
| Subjects: | |
| Online Access: | https://vb.bioscientifica.com/view/journals/vb/6/1/VB-23-0014.xml |
| _version_ | 1827382689127202816 |
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| author | Sarah Schnabellehner Marle Kraft Hans Schoofs Henrik Ortsäter Taija Mäkinen |
| author_facet | Sarah Schnabellehner Marle Kraft Hans Schoofs Henrik Ortsäter Taija Mäkinen |
| author_sort | Sarah Schnabellehner |
| collection | DOAJ |
| description | Endothelial cells (ECs) of blood and lymphatic vessels have distinct identity markers that define their specialized functions. Recently, hybrid vasculatures with both blood and lymphatic vessel-specific features have been discovered in multiple tissues. Here, we identify the penile cavernous sinusoidal vessels (pc-Ss) as a new hybrid vascular bed expressing key lymphatic EC identity genes Prox1, Vegfr3, and Lyve1. Using single-cell transcriptome data of human corpus cavernosum tissue, we found heterogeneity within pc-S endothelia and observed distinct transcriptional alterations related to inflammatory processes in hybrid ECs in erectile dysfunction associated with diabetes. Molecular, ultrastructural, and functional studies further established hybrid identity of pc-Ss in mouse, and revealed their morphological adaptations and ability to perform lymphatic-like function in draining high-molecular-weight tracers. Interestingly, we found that inhibition of the key lymphangiogenic growth factor VEGF-C did not block the development of pc-Ss in mice, distinguishing them from other lymphatic and hybrid vessels analyzed so far. Our findings provide a detailed molecular characterization of hybrid pc-Ss and pave the way for the identification of molecular targets for therapies in conditions of dysregulated penile vasculature, including erectile dysfunction. |
| first_indexed | 2024-03-08T14:25:09Z |
| format | Article |
| id | doaj.art-63461bef0c054ce58c8ba7cab392f484 |
| institution | Directory Open Access Journal |
| issn | 2516-5658 |
| language | English |
| last_indexed | 2024-03-08T14:25:09Z |
| publishDate | 2024-01-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Vascular Biology |
| spelling | doaj.art-63461bef0c054ce58c8ba7cab392f4842024-01-13T05:56:18ZengBioscientificaVascular Biology2516-56582024-01-0161115https://doi.org/10.1530/VB-23-0014Penile cavernous sinusoids are Prox1-positive hybrid vesselsSarah Schnabellehner0Marle Kraft1Hans Schoofs2Henrik Ortsäter3Taija Mäkinen4Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenEndothelial cells (ECs) of blood and lymphatic vessels have distinct identity markers that define their specialized functions. Recently, hybrid vasculatures with both blood and lymphatic vessel-specific features have been discovered in multiple tissues. Here, we identify the penile cavernous sinusoidal vessels (pc-Ss) as a new hybrid vascular bed expressing key lymphatic EC identity genes Prox1, Vegfr3, and Lyve1. Using single-cell transcriptome data of human corpus cavernosum tissue, we found heterogeneity within pc-S endothelia and observed distinct transcriptional alterations related to inflammatory processes in hybrid ECs in erectile dysfunction associated with diabetes. Molecular, ultrastructural, and functional studies further established hybrid identity of pc-Ss in mouse, and revealed their morphological adaptations and ability to perform lymphatic-like function in draining high-molecular-weight tracers. Interestingly, we found that inhibition of the key lymphangiogenic growth factor VEGF-C did not block the development of pc-Ss in mice, distinguishing them from other lymphatic and hybrid vessels analyzed so far. Our findings provide a detailed molecular characterization of hybrid pc-Ss and pave the way for the identification of molecular targets for therapies in conditions of dysregulated penile vasculature, including erectile dysfunction.https://vb.bioscientifica.com/view/journals/vb/6/1/VB-23-0014.xmlendotheliumhybrid vesselvascular heterogeneity |
| spellingShingle | Sarah Schnabellehner Marle Kraft Hans Schoofs Henrik Ortsäter Taija Mäkinen Penile cavernous sinusoids are Prox1-positive hybrid vessels Vascular Biology endothelium hybrid vessel vascular heterogeneity |
| title | Penile cavernous sinusoids are Prox1-positive hybrid vessels |
| title_full | Penile cavernous sinusoids are Prox1-positive hybrid vessels |
| title_fullStr | Penile cavernous sinusoids are Prox1-positive hybrid vessels |
| title_full_unstemmed | Penile cavernous sinusoids are Prox1-positive hybrid vessels |
| title_short | Penile cavernous sinusoids are Prox1-positive hybrid vessels |
| title_sort | penile cavernous sinusoids are prox1 positive hybrid vessels |
| topic | endothelium hybrid vessel vascular heterogeneity |
| url | https://vb.bioscientifica.com/view/journals/vb/6/1/VB-23-0014.xml |
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