Crucial Role of CD40 Signaling in Vascular Wall Cells in Neointimal Formation and Vascular Remodeling After Vascular Interventions

Extracellular matrix (ECM) in the vascular wall is a highly dynamic structure composed of a set of different molecules such as elastins, collagens, fibronectin (Fn), laminins, proteoglycans, and polysaccharides. ECM undergoes remodeling processes to regulate vascular smooth muscle and endothelial cells’ proliferation, differentiation, and adhesion. Abnormalities affecting the ECM can lead to alteration in cellular behavior and from this, this can conduce to the development of pathologies. Metalloproteases play a key role in maintaining the homeostasis of ECM by mediating the cleavage of different ECM components. There are different types of metalloproteases: matrix metalloproteinases (MMPs), disintegrin and metalloproteinases (ADAMs), and ADAMs with thrombospondin motifs (ADAMTSs). ADAMTSs have been found to participate in cardiovascular physiology and diseases and specifically in aortic aneurysms. This review aims to decipher the potential role of ADAMTS proteins in the physiopathologic development of Thoracic Aortic Aneurysms (TAA) and Abdominal Aortic Aneurysms (AAA). This review will focus on what is known on the ADAMTS family involved in human aneurysms from human tissues to mouse models. The recent findings on THSD4 (encoding ADAMTSL6) mutations in TAA give a new insight on the involvement of the ADAMTS family in TAA.

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THE ROLE OF VASCULAR REMODELING IN THE FORMATION OF STRUCTURAL PHENOTYPES OF OSTEOARTHRITIS

Kuban Scientific Medical Bulletin ◽

10.25207/1608-6228-2018-25-3-61-67 ◽

2018 ◽

Vol 25 (3) ◽

pp. 61-67

Author(s):

M. A. KABALYK ◽

V. A. NEVZOROVA

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Knee Joint ◽

Vascular Remodeling ◽

Structural Changes ◽

Vascular Wall ◽

External Diameter ◽

Resonance Imaging ◽

Structural Progression

Aim. Evaluation of the role of vascular remodeling in the formation of structural phenotypes of osteoarthritis (OA).Materials and methods. 62 patients with OA aged 65,9±8,8 years and 18 volunteers without clinical and roentgenologic signs of OA aged 60,7±7,9 years were examined. All patients underwent magnetic resonance imaging of knee joints. To analyze the structural changes in the tissues of the knee joint, the WORMS protocol was used for magnetic resonance imaging. The thickness of the vascular wall, the external diameter, the vascular index (VI) were measured – the ratio of the diameter of the lumen of the vessel to the thickness of the popliteal artery (PA) wall, the branch of the upper lateral artery (LA), the medial artery of the knee (MA).Results. The analysis of the parameters of the arteries of the knee joint showed that with a subchondral OA phenotype, the thickness of the PA wall is statistically significantly larger than the cartilage phenotype, and the vascular index of the PA is significantly higher in the group of the cartilaginous phenotype. The upper LA wall was significantly thicker in the subchondral OA phenotype. VI of the upper LA was significantly lower in patients with a subchondral phenotype compared with the cartilaginous phenotype. The thickness of the MA wall was also larger with a bone phenotype, and VI with a cartilaginous phenotype.Conclusion. The results of the study showed the relationship between vascular remodeling and structural progression of OA. Changes in the vascular wall adversely affect all joint tissues, leading to their remodeling. It was established that the degree of vascular remodeling determines the formation of structural OA phenotypes. Severe vascular changes are associated with the subchondral OA phenotype.

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Abstract 360: Loss of Endothelial CXCR7 Exacerbates Wire-injury Induced Neointimal Formation

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.360 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Huifeng Hao ◽

Sheng Hu ◽

Dawei Bu ◽

Xiaogang Sun ◽

Miao Wang

Keyword(s):

Vascular Remodeling ◽

Tamoxifen Treatment ◽

Neointimal Formation ◽

Genome Wide ◽

Endothelial Repair ◽

A Genome ◽

Artery Disease

CXCR7 is a non-classical chemokine receptor for CXCL12, whose gene represents a genome-wide association locus for coronary artery disease. Global deletion of CXCR7 increased experimentally induced neointimal formation and atherosclerosis in hyperlipidemic mice, with evidence that CXCR7 modified cholesterol uptake to adipose tissue. We found that CXCR7 was expressed in endothelial cells of mouse neointima and human aortic lesions. To examine a role of endothelial CXCR7 in vascular remodeling, endothelial CXCR7 inducible knockout mice were studied for their vascular response to wire injury in femoral arteries. Tamoxifen treatment of mice harboring floxed CXCR7 and Cdh5 -promoter driven CreERT2 , essentially abolished endothelial CXCR7 expression in vitro and in vivo. Postnatal deletion of endothelial CXCR7 exacerbated neointimal formation on normalipidemic background, four weeks after injury. Mechanistically, this was attributable to attenuated endothelial repair following endothelial injury. Collectively, endothelial CXCR7 is a key regulator of vascular remodeling, independent of lipid traits.

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Lysophosphatidic acid-induced vascular neointimal formation in mouse carotid arteries is mediated by the matricellular protein CCN1/Cyr61

AJP Cell Physiology ◽

10.1152/ajpcell.00227.2016 ◽

2016 ◽

Vol 311 (6) ◽

pp. C975-C984 ◽

Cited By ~ 5

Author(s):

Feng Hao ◽

Fuqiang Zhang ◽

Daniel Dongwei Wu ◽

Dong An ◽

Jing Shi ◽

...

Keyword(s):

Lysophosphatidic Acid ◽

Vascular Remodeling ◽

Carotid Arteries ◽

In Vivo Model ◽

Matricellular Protein ◽

Neointimal Formation ◽

Lpa Receptor

Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low-density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation. By using LPA infusion of carotid artery in a mouse model, we demonstrated that LPA highly induced CCN1 expression (approximately six- to sevenfold) in neointimal lesions. Downregulation of CCN1 expression with the specific CCN1 siRNA in carotid arteries blocked LPA-induced neointimal formation, indicating that CCN1 is essential in LPA-induced neointimal formation. We then used LPA receptor knockout (LPA1−/−, LPA2−/−, and LPA3−/−) mice to examine LPA receptor function in CCN1 expression in vivo and in LPA-induced neointimal formation. Our data reveal that LPA1 deficiency, but not LPA2 or LPA3 deficiency, prevents LPA-induced CCN1 expression in vivo in mouse carotid arteries. We also observed that LPA1 deficiency blunted LPA infusion-induced neointimal formation, indicating that LPA1 is the major mediator for LPA-induced vascular remodeling. Our in vivo model of LPA-induced neointimal formation established a key role of the ECM protein CCN1 in mediating LPA-induced neointimal formation. Our data support the notion that the LPA1-CCN1 axis may be the central control for SMC migration and vascular remodeling. CCN1 may serve as an important vascular disease marker and potential target for vascular therapeutic intervention.

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465 Vascular Remodeling of Tumor Blood Vessels as a Result of Anti-angiogenic Therapy – the Role of Vascular Wall-resident Mesenchymal Stem Cells Within These Processes

European Journal of Cancer ◽

10.1016/s0959-8049(12)71138-3 ◽

2012 ◽

Vol 48 ◽

pp. S112

Author(s):

D. Klein ◽

N. Meißner ◽

V. Kleff ◽

H. Reis ◽

M. Yamaguchi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Blood Vessels ◽

Vascular Remodeling ◽

Vascular Wall ◽

Angiogenic Therapy ◽

Tumor Blood Vessels

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Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00501.2009 ◽

2010 ◽

Vol 298 (1) ◽

pp. H66-H74 ◽

Cited By ~ 15

Author(s):

Sheik J. Khan ◽

Si Pham ◽

Yunteo Wei ◽

Dania Mateo ◽

Melissa St-Pierre ◽

...

Keyword(s):

Oxidative Stress ◽

Smooth Muscle ◽

Vascular Injury ◽

Vascular Wall ◽

Galactosidase Activity ◽

Neointimal Formation ◽

Normal Cells ◽

The Media ◽

Vascular Senescence

This study aims to demonstrate the role of stress-induced senescence in aged-related neointimal formation. We demonstrated that aging increases senescence-associated β-galactosidase activity (SA-β-Gal) after vascular injury and the subsequent neointimal formation (neointima-to-media ratio: 0.8 ± 0.2 vs. 0.54 ± 0.15) in rats. We found that senescent cells (SA-β-Gal+ p21+) were scattered throughout the media and adventitia of the vascular wall at day 7 after injury and reached their maximum number at day 14. However, senescent cells only persisted in the injured arteries of aged animals until day 30. No senescent cells were observed in the noninjured, contralateral artery. Interestingly, vascular senescent cells accumulated genomic 8-oxo-7,8-dihydrodeoxyguanine, indicating that these cells were under intense oxidative stress. To demonstrate whether senescence worsens intimal hyperplasia after injury, we seeded matrigel-embedded senescent and nonsenescent vascular smooth muscle cells around injured vessels. The neointima was thicker in arteries treated with senescent cells with respect to those that received normal cells (neointima-to-media ratio: 0.41 ± 0.105 vs. 0.26 ± 0.04). In conclusion, these results demonstrate that vascular senescence is not only a consequence of postinjury oxidative stress but is also a worsening factor for neointimal development in the aging vasculature.

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