Penile cavernous sinusoids are Prox1-positive hybrid vessels

Area of Science:

• Vascular biology
• Endocrinology
• Cellular and Molecular Medicine

Background:

• Blood and lymphatic endothelial cells (ECs) possess distinct markers defining their functions.
• Hybrid vasculatures with mixed EC features are found in various tissues.
• Penile cavernous sinusoidal vessels (pc-Ss) were previously uncharacterized regarding their vascular identity.

Purpose of the Study:

• To identify the molecular and functional characteristics of penile cavernous sinusoidal vessels (pc-Ss).
• To investigate the role of pc-Ss in health and disease, particularly erectile dysfunction.
• To determine if pc-Ss represent a novel hybrid vascular bed.

Main Methods:

• Single-cell transcriptome analysis of human corpus cavernosum tissue.
• Molecular, ultrastructural, and functional studies in mouse models.
• Analysis of gene expression, including lymphatic EC identity genes (Prox1, Vegfr3, Lyve1).
• Functional assays assessing lymphatic-like drainage capabilities.

Main Results:

• Penile cavernous sinusoidal vessels (pc-Ss) were identified as a hybrid vascular bed expressing lymphatic EC markers (Prox1, Vegfr3, Lyve1).
• Transcriptome data revealed endothelial cell heterogeneity and inflammatory alterations in pc-Ss linked to diabetic erectile dysfunction.
• pc-Ss demonstrated lymphatic-like function in draining high-molecular-weight tracers.
• pc-Ss development in mice was independent of VEGF-C, distinguishing them from other lymphatic vessels.

Conclusions:

• Penile cavernous sinusoidal vessels (pc-Ss) are a novel hybrid vascular type with unique molecular and functional properties.
• Dysregulation of pc-Ss may contribute to erectile dysfunction, especially in diabetic patients.
• These findings offer potential molecular targets for therapeutic interventions in penile vascular disorders.