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Mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases
- Source :
- Biochemical Society Transactions
- Publication Year :
- 2021
- Publisher :
- Portland Press Ltd., 2021.
-
Abstract
- In contrast with the heart, the adult mammalian vasculature retains significant remodelling capacity, dysregulation of which is implicated in disease development. In particular, vascular smooth muscle cells (VSMCs) play major roles in the pathological vascular remodelling characteristic of atherosclerosis, restenosis, aneurysm and pulmonary arterial hypertension. Clonal lineage tracing revealed that the VSMC-contribution to disease results from the hyperproliferation of few pre-existing medial cells and suggested that VSMC-derived cells from the same clone can adopt diverse phenotypes. Studies harnessing the powerful combination of lineage tracing and single-cell transcriptomics have delineated the substantial diversity of VSMC-derived cells in vascular lesions, which are proposed to have both beneficial and detrimental effects on disease severity. Computational analyses further suggest that the pathway from contractile VSMCs in healthy arteries to phenotypically distinct lesional cells consists of multiple, potentially regulatable, steps. A better understanding of how individual steps are controlled could reveal effective therapeutic strategies to minimise VSMC functions that drive pathology whilst maintaining or enhancing their beneficial roles. Here we review current knowledge of VSMC plasticity and highlight important questions that should be addressed to understand how specific stages of VSMC investment and phenotypic diversification are controlled. Implications for developing therapeutic strategies in pathological vascular remodelling are discussed and we explore how cutting-edge approaches could be used to elucidate the molecular mechanisms underlying VSMC regulation.
- Subjects :
- Vascular smooth muscle
Cell
Myocytes, Smooth Muscle
Clone (cell biology)
Gene Expression
Disease
Biology
Biochemistry
Muscle, Smooth, Vascular
Vascular remodelling in the embryo
Transcriptome
lineage tracing
cardiovascular disease
Cell Plasticity
single cell RNA sequencing
medicine
Animals
Humans
Cell Lineage
Review Articles
Cell Proliferation
cell plasticity
Gene Expression & Regulation
musculoskeletal system
Atherosclerosis
Phenotype
medicine.anatomical_structure
Gene Expression Regulation
Cardiovascular System & Vascular Biology
vascular smooth muscle
Cell Cycle, Growth & Proliferation
cardiovascular system
Epigenetics
Neuroscience
Signal Transduction
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Biochemical Society Transactions
- Accession number :
- edsair.doi.dedup.....4af9e3b26f400aa5f0bf0d0a7ba27218
- Full Text :
- https://doi.org/10.17863/cam.74510