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Page 6 of 9 Kovacs et al. Vessel Plus 2018;2:15 I http://dx.doi.org/10.20517/2574-1209.2018.06

LPS/E.coli Sepsis I/R Cigarette smoke

Tubacin [19,70] Butyrate [63]
Panobinostatand trichostatin [20] Sodium butyrate and trichostatin [64]
RGFP-966 [20] Valproicacid [65-67]
Tubastatin A and CAY10603 [61,62] Suberanilohydroxamicacid [68]

Actin stress fiber formation and cell contraction Production of TNF-α,CINC-1, IL-1β, IL-6, NO
α-tubulin deacetylation and microtubules destabilization Expression of ICAM-1, E-selectin and NF-κBp65
β-catenin deacetylation and disassembly of adherens junctions MPO activation
Phosphorylation of MLC and endothelial cell hyperpermeability Lung infiltration of inflammatory cells
Caspase-3 activation Histopathological changes
Activation of Hsp90 and RhoAsignaling

Endothelial barrier dysfunction, lung edema and inflammation

Acute lung injury

Figure 1. Schematic illustration of role of HDACs in acute lung injury (ALI). HDAC inhibitors: Tubacin (N1-[4-[(2R,4R,6S)-4-[[(4,5-
diphenyl-2-oxazolyl)thio]methyl]-6-[4-(hydroxymethyl)phenyl]-1,3-dioxan-2-yl]phenyl]-N8-hydroxy-octanediamide) [19,70] ; Panobinostat
(NVP-LBH589) [20] ; Trichostatin A (TSA, 7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6R-dimethyl-7-oxo-2E,4E-heptadienamide) [20,64] ;
RGFP-966 ((2E)-N-(2-Amino-4-fluorophenyl)-3-[(2E)-1-(3-phenyl-2-propen-1-yl)-1H-pyrazol-4-yl]-2-propenamide) [20] ; Tubastatin
A (N-hydroxy-4-[(1,2,3,4-tetrahydro-2-methyl-5H-pyrido[4,3-b]indol-5-yl)methyl]-benzamide) [61,62] ; CAY10603 (N-[4-[3-[[[7-
(hydroxyamino)-7-oxoheptyl]amino]carbonyl]-5-isoxazolyl]phenyl]-1,1-dimethylethyl ester, carbamic acid) [61,62] ; Sodium Butyrate
(butanoic acid sodium salt) [63,64] ; Valproic acid (VPA, 2-Propylpentanoic acid) [65-67] ; Vorinostat (Suberoylanilide Hydroxamic Acid,
SAHA) [68] . LPS: lipopolysaccharides; E.coli: Escherichia coli; I/R: ischemia-reperfusion; MLC: myosin light chain; TNF-α: tumor necrosis
factor-α; CINC-1: cytokine-induced neutrophil chemoattractant-1; IL-1β: interleukin 1β; IL-6: interleukin 6; NO: nitric oxide; ICAM-1:
intercellular adhesion molecule 1; NF-κB p65: nuclear factor kappa-B p65 subunit; MPO: myeloperoxidase

DECLARATIONS
Authors’ contributions
Concept/design: Kovacs L, Kovacs-Kasa A, Su Y
Draft: Kovacs L, Kovacs-Kasa A
Manuscript editing and review: all authors

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by NIH/NHLBI R01 HL134934 (YS), VA Merit Review Award BX002035
(YS), Flight Attendants Medical Research Institute grant 140083_CIA (YS), AHA Career Development
Award 18CDA34110225 (LK) and AHA Postdoctoral Fellowship 18POST33990193 (AKK).

Conflicts of interest
All authors declare that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.