Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 405

Tabl e 8. 8. Vascular smooth myocyte phenotypes (Sources: [ 747 , 748 ]). These cells can repro-
gram their expression pattern according to environmental conditions. These changes can trigger
chromatin remodeling especially using acetylation and methylation of histones that modifies DNA
accessibility to transcription factors, such as Kruppel-like factor KLF4, P300, myocardin, and
serum responsive factor (SRF). In fact, numerous chromatin regulators act at SMC-specific marker
sites to silence or enable access to the transcriptional machinery. Various stimuli influence the SMC
phenotype, such as transforming growth factor- β , platelet-derived growth factor, retinoic acid, and

oxidized phospholipids.

Phenotype Features

Contractile Synthesis of contractile proteins

quiescent Low proliferative rate

Synthetic Production and secretion of matrix constituents

(matrix) and and metallopeptidases

proliferative Interplay between KLF4, KLF5, and miR146a

Endocytic Uptake of modified LDLs in atheroma

and Pinocytosis of small components of the fluid phase

phagocytic Phagocytosis of molecular complexes, cell particles,

or apoptotic cells

Organizer of Acquisition of ability to migrate and proliferate

advential Production of inflammatory signals

response

Osteoblastic Calcification in atheroma

8.5.3 Vascular Smooth Myocyte Phenotypes

Vascular smooth myocytes have various subtypes that prevent easy identification in
histological sections. Moreover, their fate oscillates from quiescent, differentiated,
contractile cells to proliferative cells, according to types of local environmental
signals (Table 8.8 ). The vSMC phenotype is controlled by interactions between
general and SMC-specific factors. Phenotype change is a rapid adaptation to
fluctuating environmental cues.
Vascular smooth myocyte reprogramming relies on chromatin remodeling that
results from acetylation and methylation of histones. 30

30 Nucleic DNA is packaged into chromatin, the core structure of which is nucleosome. The
chromatin state mainly depends on histone modifications ( epigenetic reprogramming ). Modifi-
cations of histones in nucleosomes can determine gene expression. In nucleosomes, DNA is
wrapped by an octamer that contains 2 molecules of core histones H2a, H2b, H3, and H4,
which is stabilized by the linker histone H1 (Vol. 1 - Chap. 4. Cell Structure and Function). N-
termini of core histones contain flexible protease-sensitive tails that are sites of post-translational
modifications, such as acetylation, adpribosylation, methylation, phosphorylation, and ubiquiti-
nation. These modifications allow or forbid access to machineries involved in DNA replication,
chromatin assembly, and gene transcription. Histone acetylation can activate transcription; histone