Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Science. 2024 Feb 9;383(6683):eade8064. doi: 10.1126/science.ade8064.
Penile erection is mediated by the corpora cavernosa, a trabecular-like vascular bed that enlarges upon vasodilation, but its regulation is not completely understood. Here, we show that perivascular fibroblasts in the corpora cavernosa support vasodilation by reducing norepinephrine availability. The effect on penile blood flow depends on the number of fibroblasts, which is regulated by erectile activity. Erection dynamically alters the positional arrangement of fibroblasts, temporarily down-regulating Notch signaling. Inhibition of Notch increases fibroblast numbers and consequently raises penile blood flow. Continuous Notch activation lowers fibroblast numbers and reduces penile blood perfusion. Recurrent erections stimulate fibroblast proliferation and limit vasoconstriction, whereas aging reduces the number of fibroblasts and lowers penile blood flow. Our findings reveal adaptive, erectile activity-dependent modulation of penile blood flow by fibroblasts.
阴茎勃起是由海绵体介导的，海绵体是一种类似小梁的血管床，在血管扩张时会增大，但它的调节机制尚不完全清楚。在这里，我们表明海绵体中的血管周成纤维细胞通过减少去甲肾上腺素的可用性来支持血管舒张。对阴茎血流的影响取决于成纤维细胞的数量，而后者受勃起活动的调节。勃起会动态改变成纤维细胞的位置排列，暂时下调 Notch 信号。抑制 Notch 会增加成纤维细胞的数量，从而提高阴茎血流。持续的 Notch 激活会降低成纤维细胞的数量并减少阴茎的血液灌注。反复勃起会刺激成纤维细胞增殖并限制血管收缩，而衰老会减少成纤维细胞的数量并降低阴茎的血流。我们的研究结果揭示了成纤维细胞通过适应性、勃起活动依赖性调节阴茎血流。
