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Page 2 of 3 Gerasimovskaya et al. Vessel Plus 2019;3:11 I http://dx.doi.org/10.20517/2574-1209.2019.11
[2]
restriction and preeclampsia. Balistreri reviewed current view on the mechanisms of PHN and its
relationship with adult PH and other adult diseases. According to the recent findings, adult PH may be result
of developmental programing (DP). Vice versa, it was demonstrated that PHN could be a result of several
adverse events during perinatal life. Common risk factors include drugs and alcohol abuse, high altitude
living, and pollution. Importantly, that identification of specific risk factor may facilitate the development of
effective therapies. Genomic imprinting is the principal driver of DP. It affects newborns primarily through
maternal DNA methylation, however, other epigenetic mechanisms such as histone modifications, non-
coding RNA-mediated gene silencing, and chromatin remodeling are also likely to be involved. Mechanisms
and models of PHN summarized in the current review.

Epigenetic mechanisms have emerged as a one of the major drivers of vascular remodeling. Histone
deacetylases (HDACs) modify core histones around DNA by removing acetyl groups from hyper-acetylated
histones. More recent findings reveal that HDACs can not only deacetylate histones but many non-
histone proteins and are able to regulate numerous cellular functions such as transcription, cytoskeletal
polymerization, and signal transduction. Recently, the therapeutic potential of inhibiting HDACs for the
[3]
treatment of cardiovascular diseases has been appreciated. Kovacs et al. summarized the current view
on the role of HDAC-mediated vascular mechanisms associated with acute lung injury (ALI) progression/
preservation. ALI arises from a wide range of lung injuries such as toxins or inflammatory mediators,
resulting in significant morbidity and frequently in death. A major cause of ALI is dysfunction of the
pulmonary vascular endothelial barrier resulting in pulmonary infiltrates, hypoxemia and pulmonary
edema. It was recently demonstrated that pharmacologic inhibition of several HDACs leads to enhancement
of pulmonary vascular barrier, thereby, preventing the development of ALI. However, the mechanisms of
HDAC-mediated vascular barrier preservation are ill defined. The current article provides the functional
characterization of HDACs with the emphasis on their role in the regulation of endothelial barrier.

VSMC are the predominant cell type controlling large blood vessel stiffness and blood pressure. They switch
between alternate phenotypes of contractile in non-pathological settings to the pathological synthetic-
[4]
proliferative phenotype, associated with cardiovascular disease. In their review, Ahmed et al. 2018 focus on
the role of VSMC under physiological conditions and blood vessel physiology and describe how stiffening of
large arteries could be transmitted to the microcirculation of organs such as the heart and lungs. The authors
describe in a simplistic manner how different molecules and structures result in the transition between
contractile vs. synthetic-proliferative VSMC phenotype, through the mechanisms that involve of cytoskeletal
proteins, myosin light chains (MLC-20, MLC-17), and myosin isoforms. They emphasize complex crosstalk
between VSMCs and their surrounding matrix in healthy and in pathological conditions thus providing new
insights into the mechanisms that regulate the phenotypic switch.

Thrombospondin (TSP) is a family of structurally related proteins with five distinct members (TSP1-5)
that bind to surface receptors such as CD36 or the αvβ3 and αIIbβ3 integrins to regulate diverse biological
processes like inflammation, immunity, control of extracellular matrix properties and composition, as
[5]
well as glucose and insulin metabolism. The article of Stenina-Adognravi et al. reviews the contribution
of TSPs to regulation of cancer growth and describes various functions of TSPs that link these proteins by
modulating multiple physiological and pathological events that prevent or support tumor development. TSP1
and TSP2 have major role in vascular tissues, participate in platelet aggregation, and are anti-angiogenic
whereas TSP4 is pro-angiogenic and pro-inflammatory in tumor models. TSP4 has shown to have a role in
tumor growth and angiogenesis. TSP3 and 5 have major roles in bone development and deletion of the gene
impairs skeletal development in mice. The authors summarize studies of TSP functions and roles in different
systems of the organism and the complex nature of TSP interactions and functions, including their different
cell- and tissue-specific effects.