Angiopoietin-1: Can be produced by endothelial cells and act in an autocrine agonistic manner?

BACKGROUND: The source of Ang1 is controversial. Although some people think that human endothelial cells can produce Ang1, more believe that endothelial cells produce Ang2 but not Ang1. However, in our recent study on endothelial cells and angiogenesis, we find that endothelial cells do produce Ang1. OBJECTIVE: This study aims to prove that endothelial cells can produce Ang1 and explore what manner does Ang1 act in. METHODS: Immunohistochemistry, western blotting and reverse transcription PCR were used to prove if human dermal microvascular endothelial cells, human brain microvascular endothelial cells and human umbilical vein endothelial cells produce Ang1. In order to explore Ang1's act manner, Ang1 expression of human dermal microvascular endothelial cells pre-treated by propranolol IC50 was detected by western blotting. RESULTS: Immunohistochemistry, western blotting and reverse transcription PCR showed that human dermal microvascular endothelial cells, human brain microvascular endothelial cells and human umbilical vein endothelial cells all expressed Ang1, and propranolol significantly inhibited Ang1 expression of human dermal microvascular endothelial cells. CONCLUSIONS: Endothelial cells can also produce Ang1. In addition, endogenous Ang1 may be an autocrine agonistic regulator, participating in endothelial cells angiogenesis process.

Phentolamine inhibits angiogenesis in vitro: Suppression of proliferation migration and differentiation of human endothelial cells.

It is widely known that the ß-adrenergic receptor (AR) blocker (propranolol) inhibits human endothelial cell (EC) angiogenesis in vitro, but how the α-AR antagonist (phentolamine) affects human EC angiogenesis has not yet been studied. Here, we show for the first time that both human dermal microvascular ECs (HDMECs) and human brain microvascular ECs (HBMECs) express α-ARs. Moreover, our results indicate that phentolamine inhibits the proliferation, migration, and tubulogenesis of HDMECs and HBMECs. Finally, VEGFR-2 and Ang1/2 expression of HDMECs was suppressed by phentolamine. Together, these results indicate that phentolamine impairs several critical events of neovascularization, and α-ARs, as well as the VEGF/VEGFR-2 and Ang/Tie-2 signaling pathways, may be involved in these processes. Our results suggest a novel therapeutic strategy for the use of α-blockers in the treatment of human angiogenesis-dependent diseases.

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

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 ß-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.

Norepinephrine Regulates Keratinocyte Proliferation to Promote the Growth of Hair Follicles.

Psychological factors and stress can cause hair loss. The sympathetic-adrenal-medullary (SAM) axis has been reported to regulate the growth of hair follicles (HF). The sympathetic nerve is a component of the SAM axis, but it has not been sufficiently or convincingly linked to hair growth. In this study, we demonstrate that chemical sympathectomy via administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to mice inhibited HF growth, but treatment with the ß-adrenoceptor antagonist propranolol (PR) had no effect. HF length and skin thickness were greater in PR-treated and control mice than in 6-OHDA-treated mice, as evidenced by hematoxylin and eosin staining. Furthermore, we found that the reduced HF growth in sympathectomized animals was accompanied by a decreased keratinocyte proliferation. Moreover, the neurotransmitter norepinephrine (NE) was found to efficiently promote HF growth in an organotypic skin culture model. Together, these findings suggest that sympathetic nerves regulate keratinocyte behaviors to promote hair growth, providing novel insights into stress-related, chemotherapy-, and radiotherapy-induced alopecia.