Sympathetic nerves: How do they affect angiogenesis, particularly during wound healing of soft tissues?

Abstract

Angiogenesis is essential for wound healing, and angiogenesis impairment can result in chronic ulcers. Studies have shown that the sympathetic nervous system has an important role in angiogenesis. In recent years, researchers have focused on the roles of sympathetic nerves in tumor angiogenesis. In fact, sympathetic nerves can affect angiogenesis in the wound healing of soft tissues, and may have a similar mechanism of action as that seen in tumorigenesis. Sympathetic nerves act primarily through interactions between the neurotransmitters released from nerve endings and receptors present in target organs. Among this, activation or inhibition of adrenergic receptors (mainly β-adrenergic receptors) influence formation of new blood vessels considerably. As sympathetic nerves locate near pericytes in microvessel, go along the capillaries and there are adrenergic receptors present in endothelial cells and pericytes, sympathetic nerves may participate in angiogenesis by influencing the endothelial cells and pericytes of new capillaries. Studying the roles of sympathetic nerves on the angiogenesis of wound healing can contribute to understanding the mechanisms of tissue repair, tissue regeneration, and tumorigenesis, thereby providing new therapeutic perspectives.

Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model

“…The enhanced expression of angiogenic factors in ECM/SVF-gel and a rich vascular network around the wound area indicated that the faster healing of wounds in the ECM/SVF-gel group could be attributed to increased vascularization. Vascularization of the wound bed is known to play a significant role in the wound healing process [ 13 , 14 ]. Recent cytotherapy strategies using MSCs have aimed at increasing vascularization to achieve wound healing due to their paracrine effects and differentiating potential [ 15 , 16 ].…”

Sympathetic Denervation Accelerates Wound Contraction but Inhibits Reepithelialization and Pericyte Proliferation in Diabetic Mice

“…The relationship between these three features in the diabetic foot is not completely clear. Sympathetic nerve activity may correlate with reepithelialization, neurogenic inflammation [12], collagen metabolism, and angiogenesis [6]. The role of sympathetic nerve failure in DFUs remains controversial.…”

“…The role of sympathetic nerve failure in DFUs remains controversial. Sympathetic nerves are located near pericytes in the microvessels [6]. It has not been reported how sympathetic denervation affects inflammation and angiogenesis in DFUs.…”

“…The number of hematopoietic stem and progenitor cells (HSPC) mobilized by granulocyte colony-stimulating factor was dramatically reduced in 6-OHDA-lesioned mice [38]. Adrenergic receptors were found to be present in endothelial cells and pericytes [6]. Therefore, reduced levels of pericytes in 6-OHDA-treated diabetic mice may be due to abrogated HSPC migration.…”

“…In contrast to nondiabetic wounds, diabetic wounds are characterized by prolonged inflammation, delayed wound closure [3], and impaired angiogenesis [4]. The neuroimmune axis and successful angiogenesis are essential for DFU healing [5, 6]. Although great progress has been made in the treatment of DFUs, they remain difficult to fully cure.…”