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

Article type: Research Article

Authors: Pan, Liangli^{a; b; c; 1} | Liu, Chenyang^{a; 1} | Kong, Yanan^{a; b} | Piao, Zhengguo^{c; *} | Cheng, Biao^{a; b; d; e; *}

Affiliations: [a] Southern Medical University, Guangzhou, China | [b] Department of Plastic Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China | [c] Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, China | [d] Center of Wound Treatment, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China | [e] The Key Laboratory of Trauma Treatment & Tissue Repair of Tropical Area, PLA, Guangzhou, China

Correspondence: [*] Corresponding author: Biao Cheng, Department of Plastic Surgery, Guangzhou General Hospital of Guangzhou Military Command, PLA, Guangzhou 510010, Guangdong Province, China. Tel.: +86 20 88653337; Fax: +86 20 36222169; E-mail: chengbiaocheng@163.com.

Correspondence: [*] Corresponding author: Zhengguo Piao, Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, Guangdong Province, China. Tel./Fax: +86 20 61350511; E-mail: zhengguopiao@hotmail.com.

Note: [1] These authors contributed equally to the article.

Abstract: It is widely known that the β-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.

Keywords: Phentolamine, α-adrenergic receptors, endothelial cell, angiogenesis, angiogenesis-dependent disease

DOI: 10.3233/CH-162070

Journal: Clinical Hemorheology and Microcirculation, vol. 65, no. 1, pp. 31-41, 2017