The Neuropeptide Secretoneurin Exerts a Direct Effect on Arteriogenesis In Vivo and In Vitro

Abstract

It is well known that nerves modulate the development and remodeling of blood vessels by releasing different neuropeptides and neurotransmitters. Secretoneurin (SN), a neuropeptide located in nerve fibers along blood vessels, acts as a pro‐angiogenic agent and induces postnatal vasculogenesis. However, little is known about its involvement in arteriogenesis. In the present study, we tested the hypothesis that SN promotes arteriogenesis in a rat model of hind limb ischemia, as such, we evaluated the effect of this neuropeptide on proliferation and the production of adhesion and chemotaxis molecules in vascular smooth muscle cells (VSMCs), the main component that carries the burden of the transformation of a small arteriole into a large collateral vessel. In vivo, SN‐immunoreactive nerve fibers were abundantly distributed in the adventitia of the collateral vessel. Moreover, administration of SN induced cell proliferation in the vascular wall and the infiltration of inflammatory cells/macrophages to promote collateral vessel growth. This was shown by an increased density of arterioles/arteries, together with a well‐developed network of collateral vessels, and well‐preserved skeletal muscles. In vitro, SN exerted proliferative effects on VSMCs and stimulated these cells to express adhesion molecules. In conclusion, our data demonstrate for the first time that SN acts as a mediator of inflammation, contributing to collateral vessel growth, in addition to directly stimulating cell proliferation in the vascular wall to promote collateral vessel growth in a rat model of hind limb ischemia. Anat Rec, 301:1917–1927, 2018. © 2018 Wiley Periodicals, Inc.

Effect and Molecular Mechanisms of Collateral Vessel Growth Mediated by Activation of Transient Receptor Potential Vanilloid Type 1

“…Studies have addressed the importance of active remodeling of the vascular walls in the development of collateral vessels [20]. It is conceivable that sufficient adventitial remodeling ensures the outward growth of collateral vessels and allows the formation of pre-existing small arterioles into significant conduits of blood flow [13, 21]. This is supported by our observation that active cell proliferation takes place in all layers of collateral vessels, especially in the adventitia.…”

The Emerging Roles of Chromogranins and Derived Polypeptides in Atherosclerosis, Diabetes, and Coronary Heart Disease

“…These findings suggest that catestatin and vasostatin-1 contribute to suppressing plaque progression and preserving vascular elasticity. Secretoneurin stimulates the expression of MCP-1 and VCAM-1 in VSMCs [ 115 ].…”

SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer

“…Similarly, confocal immunofluorescence microscopy showed SCG2 had an apparent colocalization with macrophages in tumor tissues. The previous study has demonstrated that SN, SCG2 derived peptide, could induce macrophage accumulation and angiogenesis ( Liu et al, 2018 ). These results indicated that high expression of SCG2 might promote M0 macrophages polarize to M2 and eventually differentiate into TAMs, enhancing tumor cell invasion, metastasis, angiogenesis, and inhibiting the anti-tumoral immune surveillance ( Kim and Bae, 2016 ), predict a worse prognosis of CRC patients ( Waniczek et al, 2017 ).…”