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Development and pathologies of the arterial wall

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Abstract

Arteries consist of an inner single layer of endothelial cells surrounded by layers of smooth muscle and an outer adventitia. The majority of vascular developmental studies focus on the construction of endothelial networks through the process of angiogenesis. Although many devastating vascular diseases involve abnormalities in components of the smooth muscle and adventitia (i.e., the vascular wall), the morphogenesis of these layers has received relatively less attention. Here, we briefly review key elements underlying endothelial layer formation and then focus on vascular wall development, specifically on smooth muscle cell origins and differentiation, patterning of the vascular wall, and the role of extracellular matrix and adventitial progenitor cells. Finally, we discuss select human diseases characterized by marked vascular wall abnormalities. We propose that continuing to apply approaches from developmental biology to the study of vascular disease will stimulate important advancements in elucidating disease mechanism and devising novel therapeutic strategies.

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Abbreviations

AAA:

Abdominal aortic aneurysm

ADCL:

Autosomal dominant cutis laxa

ALK1:

Activin receptor-like kinase 1

BMP:

Bone morphogenetic protein

CADASIL:

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

DIT:

Diffuse intimal thickening

E:

Embryonic day

EC:

Endothelial cell

ECM:

Extracellular matrix

EMT:

Epithelial-to-mesenchymal transition

FGF:

Fibroblast growth factor

hESC:

Human embryonic stem cell

IL:

Interleukin

IPAH:

Idiopathic pulmonary arterial hypertension

iPSC:

Induced pluripotent stem cell

ISV:

Intersegmental vessel

JAG1:

Jagged 1

LDS:

Loeys–Dietz syndrome

LPM:

Lateral plate mesoderm

LTBP:

Latent TGFβ binding protein

MFS:

Marfan syndrome

MI:

Myocardial infarction

MMPs:

Matrix metalloproteases

P:

Postnatal day

PA:

Pulmonary artery

PAH:

Pulmonary arterial hypertension

PAP:

Pulmonary arterial pressure

PDGF:

Platelet-derived growth factor

PH:

Pulmonary hypertension

PSM:

Presomitic mesoderm

RV:

Right ventricle

S1PR1:

Sphingosine 1 phosphate receptor 1

SRF:

Serum response factor

SMA:

Alpha smooth muscle actin

SMC:

Smooth muscle cell

SMMHC:

Smooth muscle myosin heavy chain

STAT:

Signal transducer and activator of transcription

SVAS:

Supravalvular aortic stenosis

TAA:

Thoracic aortic aneurysm

TGF:

Transforming growth factor

TIMPs:

Tissue inhibitors of metalloproteases

VEGF:

Vascular endothelial growth factor

VSMC:

Vascular smooth muscle cell

WS:

Williams syndrome

Wt1:

Wilms tumor 1

YAC:

Yeast artificial chromosome

β-gal:

β-Galactosidase

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Acknowledgments

We thank Greif laboratory members for input. D.M.G. was supported by the Pulmonary Hypertension Association and National Institute of Health under the K08 Award (5K08HL093362). J.K.L. was supported by the National Institute of Health under the Ruth L. Kirschstein NRSA Institutional Training Grant (2T32HL007950).

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  1. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, 300 George St., Rm 773J, New Haven, CT, 06511, USA

    Sara B. Seidelmann, Janet K. Lighthouse & Daniel M. Greif

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  1. Sara B. Seidelmann
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  2. Janet K. Lighthouse
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  3. Daniel M. Greif
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Correspondence to Daniel M. Greif.

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S.B. Seidelmann and J.K. Lighthouse contributed equally.

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Seidelmann, S.B., Lighthouse, J.K. & Greif, D.M. Development and pathologies of the arterial wall. Cell. Mol. Life Sci. 71, 1977–1999 (2014). https://doi.org/10.1007/s00018-013-1478-y

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