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Angiopoietin-1 and Angiopoietin-2 in metabolic disorders: therapeutic strategies to restore the highs and lows of angiogenesis in diabetes

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Abstract

The morbidity and mortality of diabetes mellitus are mostly attributed to cardiovascular complications. Despite tremendous advancement in glycemic control, anti-diabetic medications have failed to revert vascular impairment once triggered by the metabolic disorder. The angiogenic growth factors, Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2), are crucial regulators of vessel formation and maintenance starting with embryonic development and continuing through life. In mature vessels, angiopoietins control vascular permeability, inflammation and remodeling. A crucial role of angiopoietins is to drive vascular inflammation from the active to the quiescent state, enabling restoration of tissue homeostasis. The mechanism is of particular importance for healing and repair after damage, two conditions typically impaired in metabolic disorders. There is an emerging body of evidences suggesting that the imbalance of Ang1 and Ang2 regulation, leading to an increased Ang2/Ang1 ratio, represents a culprit of the vascular alterations of patients with type-2 diabetes mellitus. Pharmacological modulation of Ang1 or Ang2 actions may help prevent or delay the onset of diabetic vascular complications by restoring vessel function, favoring tissue repair and maintaining endothelial quiescence. In this review, we present a summary of the role of Ang1 and Ang2, their involvement in diabetic complications, and novel therapeutic strategies targeting angiopoietins to ameliorate vascular health in metabolic disorders.

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Acknowledgments

The authors thank Marie-Hélène Hayles for revision of the English text.

Funding

This work was supported by the Italian Ministry of Instruction, University and Research (MIUR) Grant FIRB Futuro in Ricerca RBFR10URHP.

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  1. Department of Experimental Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy

    A. M. Isidori, M. A. Venneri & D. Fiore

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  1. A. M. Isidori
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  2. M. A. Venneri
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  3. D. Fiore
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Correspondence to A. M. Isidori.

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A. M. I. has been an occasional consultant for Otsuka, Shire, Novartis, and Menarini. All other authors have nothing to disclose.

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Informed consent was obtained from all individual participants included in the study.

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This review has been commissioned to Andrea M. Isidori winner of the Italian Society of Endocrinology “Under 40 SIE award” for the year 2015.

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Isidori, A.M., Venneri, M.A. & Fiore, D. Angiopoietin-1 and Angiopoietin-2 in metabolic disorders: therapeutic strategies to restore the highs and lows of angiogenesis in diabetes. J Endocrinol Invest 39, 1235–1246 (2016). https://doi.org/10.1007/s40618-016-0502-0

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