Image‐based assessment of microvascular function and structure in collagen XV‐ and XVIII‐deficient mice

Rygh, Cecilie Brekke; Løkka, Guro; Heljasvaara, Ritva; Taxt, Torfinn; Pavlin, Tina; Sormunen, Raija; Pihlajaniemi, Taina; Curry, Fitz Roy E; Tenstad, Olav; Reed, Rolf K.

doi:10.1113/jphysiol.2013.263574

Cited by 15 publications

(15 citation statements)

References 30 publications

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“…In addition to these findings, Col15a1 −/− mice are more prone to exercise-induced muscle injury than their wild-type counterparts [49]. Despite the anti-angiogenic properties of restin, which is encoded in a region of the COL15A1 gene, Col15a1 −/− mice display overall normal vascular development; however, there is an increase in vascular permeability and extravascular extracellular space in their striated muscles [49, 50]. Col15a1 −/− mice present with significant cardiac defects, because type XV collagen is normally highly expressed in the heart.…”

Section: The Roles Of Various Collagen Types In Angiogenesismentioning

confidence: 99%

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Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications

Walia

Yang

Huang

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

159

126

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Background Angiogenesis is the process of neovascularization from pre-existing vasculature and is involved in various physiological and pathological processes. Inhibitors of angiogenesis, administered either as individual drugs or in combination with other chemotherapy, have been shown to benefit patients with various cancers. Endostatin, a 20-kDa C-terminal fragment of type XVIII collagen, is one of the most potent inhibitors of angiogenesis. Scope of review We discuss the biology behind endostatin in the context of its endogenous production, the various receptors to which it binds, and the mechanisms by which it acts. We focus on its inhibitory role in angiogenesis, lymphangiogenesis, and cancer metastasis. We also present emerging clinical applications for endostatin and its potential as a therapeutic agent in the form a short peptide. Major conclusions The delicate balance between pro- and anti-angiogenic factors can be modulated to result in physiological wound healing or pathological tumor metastasis. Research in the last decade has emphasized an emerging clinical potential for endostatin as a biomarker and as a therapeutic short peptide. Moreover, elevated or depressed endostatin levels in diseased states may help explain the pathophysiological mechanisms of the particular disease. General significance Endostatin was once sought after as the ‘be all and end all’ for cancer treatment; however, research throughout the last decade has made it apparent that endostatin’s effects are complex and involve multiple mechanisms. A better understanding of newly discovered mechanisms and clinical applications still has the potential to lead to future advances in the use of endostatin in the clinic.

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Section: The Roles Of Various Collagen Types In Angiogenesismentioning

confidence: 99%

“…Col18a1 −/− mice display decreased proximal tubule integrity, softened glomeruli, and effacement of their podocytes [73]. Overall, the vascular effects of the lack of type XVIII collagen are increases in blood flow and vessel permeability [50]. …”

Section: The Roles Of Various Collagen Types In Angiogenesismentioning

confidence: 99%

Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications

Walia

Yang

Huang

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

159

126

View full text Add to dashboard Cite

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“…It may be relevant that portal myofibroblasts secrete collagen in addition to elastin, since this combination could enhance the structural stability of the duct. Collagen XV, which was recently identified as a portal fibroblast marker, is known primarily as a structural collagen that underlies blood vessels and maintains basement membrane integrity [24, 40, 41]. It has yet not been well studied in liver, but could also conceivably provide mechanical benefits to the bile ducts.…”

Section: Potential Roles For Portal Fibroblasts In Biliary Fibrosis Bmentioning

confidence: 99%

Portal Fibroblasts in Biliary Fibrosis

Wells

2014

Curr Pathobiol Rep

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Portal fibroblasts are a minor population in the normal liver, found in the periportal mesenchyme surrounding the bile ducts. While many researchers have hypothesized that they are an important myofibroblast precursor population in biliary fibrosis, responsible for matrix deposition in early fibrosis and for recruiting hepatic stellate cells, the role of portal fibroblasts relative to hepatic stellate cells is controversial. Several papers published in the past year have addressed this point and have identified other potential roles for portal fibroblasts in biliary fibrosis. The goal of this review is to critically assess these recent studies, to highlight gaps in our knowledge of portal fibroblasts, and to suggest directions for future research.

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“…Based on my studies outlined in Chapter 2 and those conducted previously by others 23,25,104,118,153 , one possibility is that COL15A1 physically binds to fibrillar collagens and actively remodels the fibrillar collagen Lastly, the 71% reduction in lesion COL15A1 staining we observed in our SMC Col15a1 knockout mice allows us to conclude that SMC are the major producer of COL15A1 within lesions ( Figure 2C). It is intriguing to speculate that SMC are also overall a major source of collagen in atherosclerotic lesions in vivo.…”

Section: Smc Produced Col15a1 Is Important In the Formation And Organmentioning

confidence: 97%

“…Skin and masseter muscle capillaries in these animals are also compromised as they have increased microvascular permeability 25,118 .…”

Section: Col15a1 Functions As a Fibrillar Collagen Organizer Importanmentioning

confidence: 99%

"Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions"

Durgin

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Atherosclerotic plaque rupture or erosion with subsequent embolic events is a major cause of sudden death from myocardial infarction or stroke [1][2][3][4][5][6] . Plaque stability is classically characterized by a fibrous cap rich in ACTA2 + presumed smooth muscle cells (SMC) and collagen with a paucity of CD68 + presumed macrophages [7][8][9][10] . The dogma in the field is that SMC produce collagens that in turn provide tensile strength and stability to atherosclerotic plaques. This has largely been supported by evidence that SMC can produce collagens in vitro [11][12][13] . However, there is no direct evidence in vivo that SMC produce collagens as: 1) collagens are secreted molecules making it challenging to identify their cell source in vivo; and 2) recent lineage tracing studies by our lab [14][15][16] and others [17][18][19][20] have shown that marker genes used to identify cell type within lesions are nonspecific. For example, SMC marker genes (e.g. ACTA2) can be expressed by myeloid-derived cells and endothelial cells and SMC can express marker genes of macrophages (e.g. CD68 and LGALS3) [14][15][16][17][18][19][20] . Therefore major unanswered questions remained in the field as to whether SMC are the primary source of collagens in vivo and if SMC produced collagens in turn impact plaque development.We are interested in type XV collagen alpha 1 (COL15A1) as we identified Combined, these results provide the first direct evidence that a SMC-derived collagen, COL15A1, is critical in lesion development. IV DedicationI dedicate this to my grandfather, Arthur Labuz. You were the heart of my family and a testament to hard work, perseverance, and inner strength. I hope I have inherited an ounce of these qualities from you and have made you proud.V Acknowledgements

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Image‐based assessment of microvascular function and structure in collagen XV‐ and XVIII‐deficient mice

Cited by 15 publications

References 30 publications

Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications

Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications

Portal Fibroblasts in Biliary Fibrosis

"Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions"

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