Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology

Rahul S. Patil
ORCID logo ,
McKenzie E. Maloney
,
Rudolf Lucas
ORCID logo ,
David J. R. Fulton
ORCID logo ,
Vijay Patel
,
Zsolt Bagi
,
Anita Kovacs-kasa
ORCID logo ,
Laszlo Kovacs
,
Yunchao Su
ORCID logo ,
Alexander D. Verin
*
Version 1 : Received: 1 January 2024 / Approved: 3 January 2024 / Online: 3 January 2024 (07:42:38 CET)

A peer-reviewed article of this Preprint also exists.

Patil, R.S.; Maloney, M.E.; Lucas, R.; Fulton, D.J.R.; Patel, V.; Bagi, Z.; Kovacs-Kasa, A.; Kovacs, L.; Su, Y.; Verin, A.D. Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology. Biomolecules 2024, 14, 140. Patil, R.S.; Maloney, M.E.; Lucas, R.; Fulton, D.J.R.; Patel, V.; Bagi, Z.; Kovacs-Kasa, A.; Kovacs, L.; Su, Y.; Verin, A.D. Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology. Biomolecules 2024, 14, 140.

Abstract

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and as such provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may results in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in the epigenetic regulation primarily via modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extra nuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases and we will discuss the potential of their inhibitors for lung injury prevention.

Keywords

lung vascular endothelium; endothelial barrier integrity; zinc-dependent HDACs; deacetylation; HDAC inhibitors; acute lung injury; acute respiratory distress syndrome

Subject

Medicine and Pharmacology, Pulmonary and Respiratory Medicine

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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