Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis

Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process.

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Vascular Wall-Resident Multipotent Stem Cells of Mesenchymal Nature within the Process of Vascular Remodeling: Cellular Basis, Clinical Relevance, and Implications for Stem Cell Therapy

Stem Cells International ◽

10.1155/2016/1905846 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Diana Klein

Keyword(s):

Stem Cells ◽

Progenitor Cells ◽

Vascular Remodeling ◽

Vascular Function ◽

Vessel Wall ◽

Vascular Wall ◽

Multipotent Stem Cells ◽

Vascular Progenitor Cells ◽

Subendothelial Space ◽

Stem And Progenitor Cells

Until some years ago, the bone marrow and the endothelial cell compartment lining the vessel lumen (subendothelial space) were thought to be the only sources providing vascular progenitor cells. Now, the vessel wall, in particular, the vascular adventitia, has been established as a niche for different types of stem and progenitor cells with the capacity to differentiate into both vascular and nonvascular cells. Herein, vascular wall-resident multipotent stem cells of mesenchymal nature (VW-MPSCs) have gained importance because of their large range of differentiation in combination with their distribution throughout the postnatal organism which is related to their existence in the adventitial niche, respectively. In general, mesenchymal stem cells, also designated as mesenchymal stromal cells (MSCs), contribute to the maintenance of organ integrity by their ability to replace defunct cells or secrete cytokines locally and thus support repair and healing processes of the affected tissues. This review will focus on the central role of VW-MPSCs within vascular reconstructing processes (vascular remodeling) which are absolute prerequisite to preserve the sensitive relationship between resilience and stability of the vessel wall. Further, a particular advantage for the therapeutic application of VW-MPSCs for improving vascular function or preventing vascular damage will be discussed.

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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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The Role of Nitric Oxide in Stem/Progenitor Cells

Stem Cell Research International ◽

10.33140/jscr/02/01/00003 ◽

2018 ◽

Vol 2 (1) ◽

Keyword(s):

Nitric Oxide ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune System ◽

Progenitor Cells ◽

Embryonic Stem ◽

Clinical Value ◽

Immune System Diseases ◽

Function Mechanism

The research on nitric Oxide (NO) and stem cells are the focus in recent years. However, seldom do people conclude the function, mechanism and clinical value of NO in various stem cells including embryonic stem cells (ESCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs). In the present review, we evaluate the recent studies on NO in different stem cells and display the latest progresses of NO therapy for tumor, cardiovascular, neurologic and immune system diseases by stem cells.

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

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.111.238329 ◽

2012 ◽

Vol 32 (1) ◽

pp. 50-64 ◽

Cited By ~ 24

Author(s):

Zifang Song ◽

Rong Jin ◽

Shiyong Yu ◽

Anil Nanda ◽

D. Neil Granger ◽

...

Keyword(s):

Crucial Role ◽

Vascular Remodeling ◽

Vascular Wall ◽

Neointimal Formation

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Contribution of Resident Stem Cells to Liver and Biliary Tree Regeneration in Human Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms19102917 ◽

2018 ◽

Vol 19 (10) ◽

pp. 2917 ◽

Cited By ~ 20

Author(s):

Diletta Overi ◽

Guido Carpino ◽

Vincenzo Cardinale ◽

Antonio Franchitto ◽

Samira Safarikia ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Progenitor Cells ◽

Human Liver ◽

Progenitor Cell ◽

Biliary Tree ◽

Tree Regeneration ◽

Multipotent Stem Cells ◽

Resident Stem Cells ◽

Stem Cell Niches

Two distinct stem/progenitor cell populations of biliary origin have been identified in the adult liver and biliary tree. Hepatic Stem/progenitor Cells (HpSCs) are bipotent progenitor cells located within the canals of Hering and can be differentiated into mature hepatocytes and cholangiocytes; Biliary Tree Stem/progenitor Cells (BTSCs) are multipotent stem cells located within the peribiliary glands of large intrahepatic and extrahepatic bile ducts and able to differentiate into hepatic and pancreatic lineages. HpSCs and BTSCs are endowed in a specialized niche constituted by supporting cells and extracellular matrix compounds. The actual contribution of these stem cell niches to liver and biliary tree homeostatic regeneration is marginal; this is due to the high replicative capabilities and plasticity of mature parenchymal cells (i.e., hepatocytes and cholangiocytes). However, the study of human liver and biliary diseases disclosed how these stem cell niches are involved in the regenerative response after extensive and/or chronic injuries, with the activation of specific signaling pathways. The present review summarizes the contribution of stem/progenitor cell niches in human liver diseases, underlining mechanisms of activation and clinical implications, including fibrogenesis and disease progression.

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Potential implications of vascular wall resident endothelial progenitor cells

Thrombosis and Haemostasis ◽

10.1160/th07-04-0318 ◽

2007 ◽

Vol 98 (11) ◽

pp. 930-939 ◽

Cited By ~ 22

Author(s):

Derya Tilki ◽

Hans-Peter Hohn ◽

Ursula Gehling ◽

Nerbil Kilic ◽

Süleyman Ergün

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Peripheral Blood ◽

Tumor Therapy ◽

Vascular Wall ◽

Endothelial Progenitor ◽

Vascular Regeneration ◽

Predictive Role ◽

Vascular Formation

SummaryA rapidly increasing body of data suggests an essential role of endothelial progenitor cells (EPCs) in vascular regeneration, formation of new vessels in cardiovascular diseases and also in tumor vasculogenesis. Moreover, recent data obtained from clinical studies with anti-angiogenic drugs in tumor therapy or with pro-angiogenic stimuli in ischemic disorders implicate a predictive role of the number of EPCs circulating in the peripheral blood in monitoring of these diseases. However, there is still some controversial data regarding the relevance of the EPCs in vascular formation depending on models used and diseases studied. One of the essential prerequisites for a better understanding of the whole contribution of EPCs to vascular formation in adult, a process called postnatal vasculogenesis, is to identify their exact sources. We could recently discover the existence of EPCs in a distinct zone of the vascular wall of large and middle sized adult blood vessels and showed that these cells are capable to differentiate into mature endothelial cells, to form capillary sprouts in arterial ring assay and to build vasa vasorumlike structures within the vascular wall. They also can be mobilized very rapidly from the vascular wall by tumor cells. This review will discuss the functional implications of these vascular wall resident endothelial progenitor cells (VW-EPCs) in relation to those of EPCs circulating in peripheral blood or derived from the bone marrow in cardiovascular and neoplastic diseases.

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The role of oxygen transport in atherosclerosis and vascular disease

Journal of The Royal Society Interface ◽

10.1098/rsif.2019.0732 ◽

2020 ◽

Vol 17 (165) ◽

pp. 20190732 ◽

Cited By ~ 3

Author(s):

John Tarbell ◽

Marwa Mahmoud ◽

Andrea Corti ◽

Luis Cardoso ◽

Colin Caro

Keyword(s):

Blood Flow ◽

Vascular Disease ◽

Oxygen Transport ◽

Intimal Hyperplasia ◽

Hypoxia Inducible Factor ◽

Vascular Diseases ◽

Vascular Wall ◽

Vasa Vasorum ◽

Mechanical Factors

Atherosclerosis and vascular disease of larger arteries are often associated with hypoxia within the layers of the vascular wall. In this review, we begin with a brief overview of the molecular changes in vascular cells associated with hypoxia and then emphasize the transport mechanisms that bring oxygen to cells within the vascular wall. We focus on fluid mechanical factors that control oxygen transport from lumenal blood flow to the intima and inner media layers of the artery, and solid mechanical factors that influence oxygen transport to the adventitia and outer media via the wall's microvascular system—the vasa vasorum (VV). Many cardiovascular risk factors are associated with VV compression that reduces VV perfusion and oxygenation. Dysfunctional VV neovascularization in response to hypoxia contributes to plaque inflammation and growth. Disturbed blood flow in vascular bifurcations and curvatures leads to reduced oxygen transport from blood to the inner layers of the wall and contributes to the development of atherosclerotic plaques in these regions. Recent studies have shown that hypoxia-inducible factor-1α (HIF-1α), a critical transcription factor associated with hypoxia, is also activated in disturbed flow by a mechanism that is independent of hypoxia. A final section of the review emphasizes hypoxia in vascular stenting that is used to enlarge vessels occluded by plaques. Stenting can compress the VV leading to hypoxia and associated intimal hyperplasia. To enhance oxygen transport during stenting, new stent designs with helical centrelines have been developed to increase blood phase oxygen transport rates and reduce intimal hyperplasia. Further study of the mechanisms controlling hypoxia in the artery wall may contribute to the development of therapeutic strategies for vascular diseases.

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