TY - JOUR
T1 - Role of Vascular Smooth Muscle Cell Phenotypic Switching and Calcification in Aortic Aneurysm Formation Involvement of Vitamin K-Dependent Processes
AU - Petsophonsakul, Ploingarm
AU - Furmanik, Malgorzata
AU - Forsythe, Rachael
AU - Dweck, Marc
AU - Schurink, Geert Willem
AU - Natour, Ehsan
AU - Reutelingsperger, Chris
AU - Jacobs, Michael
AU - Mees, Barend
AU - Schurgers, Leon
N1 - Funding Information:
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 675111.
Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019/7
Y1 - 2019/7
N2 - Aortic aneurysm is a vascular disease whereby the ECM (extracellular matrix) of a blood vessel degenerates, leading to dilation and eventually vessel wall rupture. Recently, it was shown that calcification of the vessel wall is involved in both the initiation and progression of aneurysms. Changes in aortic wall structure that lead to aneurysm formation and vascular calcification are actively mediated by vascular smooth muscle cells. Vascular smooth muscle cells in a healthy vessel wall are termed contractile as they maintain vascular tone and remain quiescent. However, in pathological conditions they can dedifferentiate into a synthetic phenotype, whereby they secrete extracellular vesicles, proliferate, and migrate to repair injury. This process is called phenotypic switching and is often the first step in vascular pathology. Additionally, healthy vascular smooth muscle cells synthesize VKDPs (vitamin K-dependent proteins), which are involved in inhibition of vascular calcification. The metabolism of these proteins is known to be disrupted in vascular pathologies. In this review, we summarize the current literature on vascular smooth muscle cell phenotypic switching and vascular calcification in relation to aneurysm. Moreover, we address the role of vitamin K and VKDPs that are involved in vascular calcification and aneurysm.
AB - Aortic aneurysm is a vascular disease whereby the ECM (extracellular matrix) of a blood vessel degenerates, leading to dilation and eventually vessel wall rupture. Recently, it was shown that calcification of the vessel wall is involved in both the initiation and progression of aneurysms. Changes in aortic wall structure that lead to aneurysm formation and vascular calcification are actively mediated by vascular smooth muscle cells. Vascular smooth muscle cells in a healthy vessel wall are termed contractile as they maintain vascular tone and remain quiescent. However, in pathological conditions they can dedifferentiate into a synthetic phenotype, whereby they secrete extracellular vesicles, proliferate, and migrate to repair injury. This process is called phenotypic switching and is often the first step in vascular pathology. Additionally, healthy vascular smooth muscle cells synthesize VKDPs (vitamin K-dependent proteins), which are involved in inhibition of vascular calcification. The metabolism of these proteins is known to be disrupted in vascular pathologies. In this review, we summarize the current literature on vascular smooth muscle cell phenotypic switching and vascular calcification in relation to aneurysm. Moreover, we address the role of vitamin K and VKDPs that are involved in vascular calcification and aneurysm.
KW - aortic aneurysm
KW - blood vessels
KW - extracellular matrix
KW - phenotypic switching
KW - vascular calcification
KW - vascular smooth muscle cell
KW - vitamin K
KW - MATRIX GLA-PROTEIN
KW - GROWTH-FACTOR-BETA
KW - ENDOPLASMIC-RETICULUM STRESS
KW - CORONARY-HEART-DISEASE
KW - ARREST-SPECIFIC GENE
KW - OXIDATIVE STRESS
KW - ABDOMINAL-AORTA
KW - ARTERIAL CALCIFICATION
KW - ATHEROSCLEROTIC PLAQUE
KW - MYOCARDIAL-INFARCTION
U2 - 10.1161/ATVBAHA.119.312787
DO - 10.1161/ATVBAHA.119.312787
M3 - (Systematic) Review article
SN - 1079-5642
VL - 39
SP - 1351
EP - 1368
JO - Arteriosclerosis Thrombosis and Vascular Biology
JF - Arteriosclerosis Thrombosis and Vascular Biology
IS - 7
ER -