Inhibition of DNA synthesis and tube morphogenesis of cultured vascular endothelial cells by chondromodulin‐I

Hiraki, Yuji; Kono, Toshiaki; Sato, Mutsumi; Shukunami, Chisa; Kondo, Jun

doi:10.1016/s0014-5793(97)01151-4

Cited by 51 publications

(41 citation statements)

References 27 publications

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“…The expression of chondromodulin‐1 is markedly decreased in BAV compared to TAV 35. Chondromodulin‐1, expressed in the aortic valve during development, inhibits cell proliferation and angiogenesis 36. Mice deficient for chondromodulin‐1 have thickened aortic valves with new blood vessels, which is one feature also observed in human mineralised aortic valves 35.…”

Section: Pathobiologymentioning

confidence: 99%

The pathology and pathobiology of bicuspid aortic valve: State of the art and novel research perspectives

Mathieu

Bossé

Huggins

et al. 2015

The Journal of Pathology CR

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Bicuspid aortic valve is the most prevalent cardiac valvular malformation. It is associated with a high rate of long‐term morbidity including development of calcific aortic valve disease, aortic regurgitation and concomitant thoracic aortic aneurysm and dissection. Recently, basic and translational studies have identified some key processes involved in the development of bicuspid aortic valve and its morbidity. The development of aortic valve disease and thoracic aortic aneurysm and dissection is the result of complex interactions between genotypes, environmental risk factors and specific haemodynamic conditions created by bicuspid aortic valve anatomy. Herein, we review the pathobiology of bicuspid aortic valve with a special emphasis on translational aspects of these basic findings. Important but unresolved problems in the pathology of bicuspid aortic valve and thoracic aortic aneurysm and dissection are discussed, along with the molecular processes involved.

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Section: Pathobiologymentioning

confidence: 99%

The pathology and pathobiology of bicuspid aortic valve: State of the art and novel research perspectives

Mathieu

Bossé

Huggins

et al. 2015

The Journal of Pathology CR

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“…1 This avascularity is abrogated in several valvular heart diseases (VHDs). [2][3][4] Chondromodulin-I, which is an antiangiogenic factor isolated from bovine cartilage, [5][6][7][8] is also expressed in the eye and is critically involved in the maintenance. Recently, we have reported that chondromodulin-I was abundantly expressed by the valvular interstitial cells in normal cardiac valves.…”

mentioning

confidence: 99%

Local Tenomodulin Absence, Angiogenesis, and Matrix Metalloproteinase Activation Are Associated With the Rupture of the Chordae Tendineae Cordis

Kimura

Shukunami

Hakuno³

et al. 2008

Circulation

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Background-Rupture of the chordae tendineae cordis (CTC) is a well-known cause of mitral regurgitation. Despite its importance, the mechanisms by which the CTC is protected and the cause of its rupture remain unknown. CTC is an avascular tissue. We investigated the molecular mechanisms underlying the avascularity of CTC and the correlation between avascularity and CTC rupture. Methods and Results-We found that tenomodulin, which is a recently isolated antiangiogenic factor, was expressed abundantly in the elastin-rich subendothelial outer layer of normal rodent, porcine, canine, and human CTC. Conditioned medium from cultured CTC interstitial cells strongly inhibited tube formation and mobilization of endothelial cells; these effects were partially inhibited by small-interfering RNA against tenomodulin. The immunohistochemical analysis was performed on 12 normal and 16 ruptured CTC obtained from the autopsy or surgical specimen. Interestingly, tenomodulin was locally absent in the ruptured areas of CTC, where abnormal vessel formation, strong expression of vascular endothelial growth factor-A and matrix metalloproteinases, and infiltration of inflammatory cells were observed, but not in the normal or nonruptured area. In anesthetized open-chest dogs, the tenomodulin layer of tricuspid CTC was surgically filed, and immunohistological analysis was performed after several months. This intervention gradually caused angiogenesis and expression of vascular endothelial growth factor-A and matrix metalloproteinases in the core collagen layer in a time-dependent manner. Conclusions-These findings provide evidence that tenomodulin is expressed universally in normal CTC in a concentric pattern and that local absence of tenomodulin, angiogenesis, and matrix metalloproteinase activation are associated with CTC rupture.

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“…Whereas chondrocytes of the avascular cartilage produce inhibitors of angiogenesis, hypertrophic chondrocytes produce angiogenic stimulators that initiate vascularization. The expression pattern of chm-I during development and in vitro and in vivo experiments with mature chm-I suggested an important role for chm-I in the proliferation and differentiation of chondrocytes, as well as in the vascular invasion of growth plates (15,16,18). Recent studies of chm-I expression in rats provided further evidence for a regulatory role of chm-I during vasculogenesis in the retina and the vitreous body (12).…”

Section: Discussionmentioning

confidence: 99%

“…Direct involvement of chm-I in angiogenesis was shown in vitro when recombinant mature chm-I inhibited proliferation and tube morphogenesis of endothelial cells in cell culture experiments (18). Injection of mature chm-I into growing mouse osteoblastomas inhibited angiogenesis and resulted in profound inhibition of tumor growth in vivo (15).…”

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confidence: 99%

Chondromodulin I Is Dispensable during Enchondral Ossification and Eye Development

Brandau

Aszódi

Hunziker

et al. 2002

Molecular and Cellular Biology

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Chondromodulin I (chm-I), a type II transmembrane protein, is highly expressed in the avascular zones of cartilage but is downregulated in the hypertrophic region, which is invaded by blood vessels during enchondral ossification. In vitro and in vivo assays with the purified protein have shown chondrocyte-modulating and angiogenesis-inhibiting functions. To investigate chm-I function in vivo, we generated transgenic mice lacking chm-I mRNA and protein. Null mice are viable and fertile and show no morphological changes. No abnormalities in vascular invasion and cartilage development were detectable. No evidence was found for a compensating function of tendin, a recently published homologue highly expressed in tendons and also, at low levels, in cartilage. Furthermore, no differences in the expression of other angiogenic or antiangiogenic factors such as transforming growth factor ␤1 (TGF-␤1), TGF-␤2, TGF-␤3, fibroblast growth factor 2, and vascular endothelial growth factor were found. The surprising lack of phenotype in the chm-I-deficient mice suggests either a different function for chm-I in vivo than has been proposed or compensatory changes in uninvestigated angiogenic or angiogenesis-inhibiting factors. Further analysis using double-knockout technology will be necessary to analyze the function of chm-I in the complex process of enchondral ossification.

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Inhibition of DNA synthesis and tube morphogenesis of cultured vascular endothelial cells by chondromodulin‐I

Cited by 51 publications

References 27 publications

The pathology and pathobiology of bicuspid aortic valve: State of the art and novel research perspectives

The pathology and pathobiology of bicuspid aortic valve: State of the art and novel research perspectives

Local Tenomodulin Absence, Angiogenesis, and Matrix Metalloproteinase Activation Are Associated With the Rupture of the Chordae Tendineae Cordis

Chondromodulin I Is Dispensable during Enchondral Ossification and Eye Development

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