scholarly journals Role of crosstalk between endothelial cells and smooth muscle cells in vascular calcification in chronic kidney disease

2021 ◽  
Author(s):  
Yu‐Xia Zhang ◽  
Ri‐Ning Tang ◽  
Li‐Ting Wang ◽  
Bi‐Cheng Liu
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Smooth Muscle Cells ◽  
Vascular Calcification ◽  
Muscle Cells

scholarly journals TDAG51 (T-Cell Death-Associated Gene 51) Is a Key Modulator of Vascular Calcification and Osteogenic Transdifferentiation of Arterial Smooth Muscle Cells

2020 ◽  
Vol 40 (7) ◽  
pp. 1664-1679
Author(s):  
Khrystyna Platko ◽  
Paul F. Lebeau ◽  
Gabriel Gyulay ◽  
Šárka Lhoták ◽  
Melissa E. MacDonald ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Cell Death ◽  
Smooth Muscle ◽  
T Cell ◽  
Kidney Disease ◽  
Smooth Muscle Cells ◽  
Vascular Calcification ◽  
Muscle Cells ◽  
Solute Transporter

Objective: Cardiovascular disease is the primary cause of mortality in patients with chronic kidney disease. Vascular calcification (VC) in the medial layer of the vessel wall is a unique and prominent feature in patients with advanced chronic kidney disease and is now recognized as an important predictor and independent risk factor for cardiovascular and all-cause mortality in these patients. VC in chronic kidney disease is triggered by the transformation of vascular smooth muscle cells (VSMCs) into osteoblasts as a consequence of elevated circulating inorganic phosphate (P i ) levels, due to poor kidney function. The objective of our study was to investigate the role of TDAG51 (T-cell death-associated gene 51) in the development of medial VC. Methods and Results: Using primary mouse and human VSMCs, we found that TDAG51 is induced in VSMCs by P i and is expressed in the medial layer of calcified human vessels. Furthermore, the transcriptional activity of RUNX2 (Runt-related transcription factor 2), a well-established driver of P i -mediated VC, is reduced in TDAG51 −/− VSMCs. To explain these observations, we identified that TDAG51 −/− VSMCs express reduced levels of the type III sodium-dependent P i transporter, Pit-1, a solute transporter, a solute transporter, a solute transporter responsible for cellular P i uptake. Significantly, in response to hyperphosphatemia induced by vitamin D 3 , medial VC was attenuated in TDAG51 −/− mice. Conclusions: Our studies highlight TDAG51 as an important mediator of P i -induced VC in VSMCs through the downregulation of Pit-1. As such, TDAG51 may represent a therapeutic target for the prevention of VC and cardiovascular disease in patients with chronic kidney disease.

scholarly journals Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease

2016 ◽  
Vol 19 (5) ◽  
pp. 628-642 ◽  
Author(s):  
Rafael Kramann ◽  
Claudia Goettsch ◽  
Janewit Wongboonsin ◽  
Hiroshi Iwata ◽  
Rebekka K. Schneider ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Calcification ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells

Abstract WMP31: Dedifferentiation of Smooth Muscle Cells and its Potential Contribution to Pathogenesis of Intracranial Aneurysms

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mieko Oka ◽  
Nobuhiko Ohno ◽  
Takakazu Kawamata ◽  
Tomohiro Aoki
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Inflammatory Responses ◽  
Muscle Cells ◽  
Inflammatory Factors ◽  
Potential Contribution ◽  
Electron Microscopic

Introduction: Intracranial aneurysm (IA) affects 1 to 5 % in general public and becomes the primary cause of subarachnoid hemorrhage, the most severe form of stroke. However, currently, no drug therapy is available for IAs to prevent progression and rupture of lesions. Elucidation of mechanisms underlying the disease is thus mandatory. Considering the important role of vascular smooth muscle cells (SMCs) in the maintenance of stiffness of arterial walls and also in the pathogenesis of atherosclerosis via mediating inflammatory responses, we in the present study analyzed morphological or phenotypical changes of SMCs during the disease development in the lesions. Methods: We subjected rats to an IA model in which lesions are induced by increase of hemodynamic force loading on intracranial arterial bifurcations and performed histopathological analyses of induced lesions including the electron microscopic examination. We then immunostained specimens from induced lesions to explore factors responsible for dedifferentiation or migration of SMCs. In vitro study was also done to examine effect of some candidate factors on dedifferentiation or migration of cultured SMCs. Results: We first found the accumulation of SMCs underneath the endothelial cell layer mainly at the neck portion of the lesion. These cells was positive for the embryonic form of myosin heavy chain, a marker for the dedifferentiated SMCs, and the expression of pro-inflammatory factors like TNF-α. In immunostaining to explore the potential factor regulating the dedifferentiation of SMCs, we found that Platelet-derived growth factor-BB (PDGF-BB) was expressed in endothelial cells at the neck portion of IA walls. Consistently, recombinant PDGF-BB could promote the dedifferentiate of SMCs and chemo-attracted them in in vitro. Finally, in the stenosis model of the carotid artery, PDGF-BB expression was induced in endothelial cells in which high wall shear stress was loaded and the dedifferentiation of SMCs occurred there. Conclusions: The findings from the present study imply the role of dedifferentiated SMCs partially recruited by PDGF-BB from endothelial cells in the formation of inflammatory microenvironment at the neck portion of IA walls, leading to the progression of the disease.

Abstract 1680: Notch Signaling Directly Targets Msx2: Possible Role of Notch Signaling in Osteogenic Conversion of Vascular Smooth Muscle Cells and Vascular Calcification

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Takehisa Shimizu ◽  
Toru Tanaka ◽  
Tatsuya Iso ◽  
Masahiko Kurabayashi
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Notch Signaling ◽  
Vascular Calcification ◽  
Transcriptional Activity ◽  
Muscle Cells ◽  
Matrix Mineralization ◽  
Cardiovascular Morbidity And Mortality ◽  
Notch Ligands

Vascular calcification is a prominent feature of atherosclerosis and closely correlated with cardiovascular morbidity and mortality. In this study, we hypothesize that Notch signaling plays an important role in osteogenic conversion of smooth muscle cells (SMCs) and vascular calcification. <Methods and Results> Either Notch ligand-expressing cells or overexpression of Notch intracellular domains (NICDs) induced expression of Msx2, a key regulator of osteogenic conversion, in human aortic SMCs (HASMCs). In addition, overexpression of Notch1 intracellular domain (N1-ICD) markedly upregulated alkaline phosphatase (ALP) activity and matrix mineralization of HASMCs. A knockdown experiment with a small interfering RNA confirmed that Msx2, but not Runx2/Cbfa1, another key osteogenic transcription factor, is responsible for Notch1-induced osteogenic conversion of HASMCs. Furthermore, this Notch1-Msx2 pathway was independent of bone morphogenetic protein-2 (BMP-2), an osteogenic morphogen upstream of Msx2. The transcriptional activity of the Msx2 promoter was significantly enhanced by Notch ligands stimulation, whereas it was abrogated by a specific Notch signaling inhibitor. The RBP-Jk binding element within the Msx2 promoter was critical to Notch1-induced Msx2 gene expression, and correspondingly, neither N1-ICD overexpression nor Notch ligands stimulation increase the Msx2 expression or transcriptional activity of the Msx2 promoter, respectively, in RBP-Jk-deficient fibroblasts. Immunohistochemistry of human artery specimens revealed colocalization of Notch1 and Msx2 within atherosclerotic plaques, indicating a role of Notch1-Msx2 pathway in vascular calcification in vivo. These results suggest that Notch signaling directly targets Msx2, thus accelerating osteogenic conversion of HASMCs and, as a result, a formation of vascular calcification.

scholarly journals Intracellular calcium increases in vascular smooth muscle cells with progression of chronic kidney disease in a rat model

2016 ◽  
pp. gfw274 ◽  
Author(s):  
Stacey Dineen Rodenbeck ◽  
Chad A. Zarse ◽  
Mikaela L. McKenney-Drake ◽  
Rebecca S. Bruning ◽  
Michael Sturek ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Intracellular Calcium ◽  
Vascular Smooth Muscle Cells ◽  
Rat Model ◽  
Muscle Cells
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