TY - JOUR
T1 - The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections
AU - Rombouts, Karlijn B.
AU - van Merrienboer, Tara A. R.
AU - Ket, Johannes C. F.
AU - Bogunovic, Natalija
AU - van der Velden, Jolanda
AU - Yeung, Kak Khee
N1 - Funding Information:
This research was funded by the Dutch Heart Foundation/Hartstichting, Dekkerbeurs 2019T065 Senior clinical scientist grant.
Publisher Copyright:
© 2021 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.
PY - 2021/11/21
Y1 - 2021/11/21
N2 - Background: Aortic aneurysms (AA) are pathological dilations of the aorta, associated with an overall mortality rate up to 90% in case of rupture. In addition to dilation, the aortic layers can separate by a tear within the layers, defined as aortic dissections (AD). Vascular smooth muscle cells (vSMC) are the predominant cell type within the aortic wall and dysregulation of vSMC functions contributes to AA and AD development and progression. However, since the exact underlying mechanism is poorly understood, finding potential therapeutic targets for AA and AD is challenging and surgery remains the only treatment option. Methods: In this review, we summarize current knowledge about vSMC functions within the aortic wall and give an overview of how vSMC functions are altered in AA and AD pathogenesis, organized per anatomical location (abdominal or thoracic aorta). Results: Important functions of vSMC in healthy or diseased conditions are apoptosis, phenotypic switch, extracellular matrix regeneration and degradation, proliferation and contractility. Stressors within the aortic wall, including inflammatory cell infiltration and (epi)genetic changes, modulate vSMC functions and cause disturbance of processes within vSMC, such as changes in TGF-β signalling and regulatory RNA expression. Conclusion: This review underscores a central role of vSMC dysfunction in abdominal and thoracic AA and AD development and progression. Further research focused on vSMC dysfunction in the aortic wall is necessary to find potential targets for noninvasive AA and AD treatment options.
AB - Background: Aortic aneurysms (AA) are pathological dilations of the aorta, associated with an overall mortality rate up to 90% in case of rupture. In addition to dilation, the aortic layers can separate by a tear within the layers, defined as aortic dissections (AD). Vascular smooth muscle cells (vSMC) are the predominant cell type within the aortic wall and dysregulation of vSMC functions contributes to AA and AD development and progression. However, since the exact underlying mechanism is poorly understood, finding potential therapeutic targets for AA and AD is challenging and surgery remains the only treatment option. Methods: In this review, we summarize current knowledge about vSMC functions within the aortic wall and give an overview of how vSMC functions are altered in AA and AD pathogenesis, organized per anatomical location (abdominal or thoracic aorta). Results: Important functions of vSMC in healthy or diseased conditions are apoptosis, phenotypic switch, extracellular matrix regeneration and degradation, proliferation and contractility. Stressors within the aortic wall, including inflammatory cell infiltration and (epi)genetic changes, modulate vSMC functions and cause disturbance of processes within vSMC, such as changes in TGF-β signalling and regulatory RNA expression. Conclusion: This review underscores a central role of vSMC dysfunction in abdominal and thoracic AA and AD development and progression. Further research focused on vSMC dysfunction in the aortic wall is necessary to find potential targets for noninvasive AA and AD treatment options.
KW - aortic aneurysm
KW - aortic dissection
KW - pathophysiology
KW - vascular biology
KW - vascular smooth muscle cell
UR - http://www.scopus.com/inward/record.url?scp=85119517266&partnerID=8YFLogxK
U2 - 10.1111/eci.13697
DO - 10.1111/eci.13697
M3 - Review article
C2 - 34698377
JO - European Journal of Clinical Investigation
JF - European Journal of Clinical Investigation
SN - 0014-2972
ER -