Open AccessSystemic deficiency of vitronectin is associated with aortic inflammation and plaque progression in ApoE‐Knockout mice
Author(s) -
Chakravarty Devasmita,
Ray Aleepta Guha,
Chander Vivek,
Mabalirajan Ulaganathan,
Mondal Prakash Chandra,
Siddiqui Khawer N.,
Sinha Bishnu Prasad,
Konar Aditya,
Bandyopadhyay Arun
Publication year - 2022
Publication title -
faseb bioadvances
Language(s) - English
Resource type - Journals
ISSN - 2573-9832
DOI - 10.1096/fba.2021-00108
Subject(s) - inflammation , vitronectin , downregulation and upregulation , knockout mouse , apolipoprotein e , apolipoprotein b , matrix metalloproteinase , metalloproteinase , medicine , cancer research , cholesterol , biology , disease , integrin , receptor , biochemistry , gene
Optimal cell spreading and interplay of vascular smooth muscle cells (VSMC), inflammatory cells, and cell adhesion molecules (CAM) are critical for progressive atherosclerosis and cardiovascular complications. The role of vitronectin (VTN), a major cell attachment glycoprotein, in the pathogenesis of atherosclerosis remains elusive. In this study, we attempt to examine the pathological role of VTN in arterial plaque progression and inflammation. We found that, relative expression analysis of VTN from the liver of Apolipoprotein E (ApoE) Knockout mice revealed that atherosclerotic progression induced by feeding mice with high cholesterol diet (HCD) causes a significant downregulation of VTN mRNA as well as protein after 60 days. Promoter assay confirmed that cholesterol modulates the expression of VTN by influencing its promoter. Mimicking VTN reduction with siRNA in HCD fed ApoE Knockout mice, accelerated athero‐inflammation with an increase in NF‐kB, ICAM‐1, and VCAM‐1 at the site of the plaque along with upregulation of inflammatory proteins like MCP‐1 and IL‐1β in the plasma. Also, matrix metalloprotease (MMP)‐9 and MMP‐12 expression were increased and collagen content was decreased in the plaque, in VTN deficient condition. This might pose a challenge to plaque integrity. Human subjects with acute coronary syndrome or having risk factors of atherosclerosis have lower levels of VTN compared to healthy controls suggesting a clinical significance of plasma VTN in the pathophysiology of coronary artery disease. We establish that, VTN plays a pivotal role in cholesterol‐driven atherosclerosis and aortic inflammation and might be a useful indicator for atherosclerotic plaque burden and stability.