Isolation of calcifiable vesicles from aortas of rabbits fed with high cholesterol diets

Hsu, Howard H.T.; Camacho, Nancy P.; Sun, Francis; Tawfik, Ossama; Aono, Hiroshi

doi:10.1016/s0021-9150(00)00425-1

Cited by 37 publications

(36 citation statements)

References 37 publications

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“…Lipid and mineralization are coincident in plaques, 4,11 and inflammatory signals at lipid accumulation sites initiate calcification by inducing vascular smooth muscle cell (VSMC) death and vesicle release. [21][22][23][24] Vesicles contain hydroxyapatitic nanocrystals representing the initial calcification seed. Thereafter, VSMCs that have undergone osteo/chondrocytic conversion are found abutting the microcalcifications.…”

Section: Discussionmentioning

confidence: 99%

Mineral Surface in Calcified Plaque Is Like That of Bone

Duer

Friščić

Proudfoot

et al. 2008

ATVB

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Objectives-Cell biological studies demonstrate remarkable similarities between mineralization processes in bone and vasculature, but knowledge of the components acting to initiate mineralization in atherosclerosis is limited. The molecular level microenvironment at the organic-inorganic interface holds a record of the mechanisms controlling mineral nucleation. This study was undertaken to compare the poorly understood interface in mineralized plaque with that of bone, which is considerably better characterized. Methods and Results-Solid state nuclear magnetic resonance (SSNMR) spectroscopy provides powerful tools for studying the organic-inorganic interface in calcium phosphate biominerals. The rotational echo double resonance (REDOR) technique, applied to calcified human plaque, shows that this interface predominantly comprises sugars, most likely glycosaminoglycans (GAGs). In this respect, and in the pattern of secondary effects seen to protein (mainly collagen), calcified plaque strongly resembles bone. Conclusion-The similarity between biomineral formed under highly controlled (bone) and pathological (plaque) conditions suggests that the control mechanisms are more similar than previously thought, and may be adaptive. It is strong further evidence for regulation of plaque mineralization by osteo/chondrocytic vascular smooth muscle cells. Key Words: atherosclerosis Ⅲ biomineralization Ⅲ glycosaminoglycans Ⅲ nuclear magnetic resonance spectroscopy Ⅲ vascular calcification C alcification 1 is prevalent in numerous vascular pathologies and is associated with adverse clinical outcomes. Parallels have frequently been drawn between ectopic calcification processes in vessels and normal developmental osteogenesis. In fact vascular calcified material is by many criteria indistinguishable from bone, and its formation involves the participation of many cellular and molecular signaling processes underlying normal osteogenesis. 2 These include matrix vesicle release, expression of mineralizationregulating proteins by vascular smooth muscle cells (VSMCs) of the vessel wall, and the association of calcification with lipid and chronic inflammation, a hallmark of atherosclerosis. 3 Indeed vascular calcification is recognized as regulated biomineralization instead of merely passive precipitation. However questions are still unanswered concerning the mechanisms leading to the initiation of calcification in the vessel wall particularly as it occurs in different vascular environments (ie, media and intima), which do not mimic that of bone. Moreover, VSMCs can overexpress mineralization inhibitors such as matrix Gla protein (MGP) to effectively block mineralization. 4 Aspects of the molecular structure of mineralized tissues 5 can be studied by the solid state NMR (SSNMR) technique 13 C{ 31 P} rotational echo double resonance (REDOR). 6 13 C is a stable, nonradioactive, NMR-receptive isotope of carbon occurring naturally at about 1.1% abundance; similarly 31 P is a stable NMR-receptive isotope of phosphorus which however is natu...

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Section: Discussionmentioning

confidence: 99%

Mineral Surface in Calcified Plaque Is Like That of Bone

Duer

Friščić

Proudfoot

et al. 2008

ATVB

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“…It is noteworthy that vascular calcification has not been observed in either human apo(a) Tg mice (11) or cholesterol-fed Tg rabbits (20). In normal rabbits fed a diet containing fairly high cholesterol (2%), only calcifiable matrix vesicles, rather than calcified lesions, were reported in aortas (35), whereas wild-type WHHL rabbits were found to develop vascular calcification when fed a diet containing high cholesterol, vitamin D, and calcium (36) or upon reaching average age of over 15 months.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein(a) Enhances Advanced Atherosclerosis and Vascular Calcification in WHHL Transgenic Rabbits Expressing Human Apolipoprotein(a)

Sun

Unoki

Wang

et al. 2002

Journal of Biological Chemistry

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High lipoprotein(a) (Lp(a)) levels are a major risk factor for the development of atherosclerosis. The risk of elevated Lp(a) concentration is increased significantly in patients who also have high levels of low density lipoprotein (LDL) cholesterol. To test the hypothesis that increased plasma levels of Lp(a) may enhance the development of atherosclerosis in the setting of hypercholesterolemia, we generated Watanabe heritable hyperlipidemic (WHHL) transgenic (Tg) rabbits expressing human apolipoprotein(a) (apo(a)). We report here that Tg WHHL rabbits developed more extensive advanced atherosclerotic lesions than did non-Tg WHHL rabbits. In particular, the advanced atherosclerotic lesions in Tg WHHL rabbits were frequently associated with calcification, which was barely evident in non-Tg WHHL rabbits. To investigate the molecular mechanism of Lp(a)-induced vascular calcification, we examined the effect of human Lp(a) on cultured rabbit aortic smooth muscle cells and found that smooth muscle cells treated with Lp(a) showed increased alkaline phosphatase activity and enhanced calcium accumulation. These results demonstrate for the first time that Lp(a) accelerates advanced atherosclerotic lesion formation and may play an important role in vascular calcification.

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“…D, Alizarin red staining revealed that calcification occurred within the aortic tunica media. A diet-induced factor, potentially an oxylipid-containing matrix vesicle, 29,64,65,85 is required to robustly elaborate MAC in BMP2-treated, Msx2 transgenic, and uremic murine disease models. 19,84 Methods have been detailed previously.…”

Section: Aortic Macmentioning

confidence: 99%

Molecular Mechanisms of Vascular Calcification

Shao

Cai

Towler

2006

ATVB

322

256

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Abstract-Vascular calcification increasingly afflicts our aging and dysmetabolic population. Once considered a passive process, it has emerged as an actively regulated form of calcified tissue metabolism, resembling the mineralization of endochondral and membranous bone. Executive cell types familiar to bone biologists, osteoblasts, chondrocytes, and osteoclasts, are seen in calcifying macrovascular specimens. Lipidaceous matrix vesicles, with biochemical and ultrastructural "signatures" of skeletal matrix vesicles, nucleate vascular mineralization in diabetes, dyslipidemia, and uremia. Skeletal morphogens (bone morphogenetic protein-2 (BMP) and BMP4 and Wnts) divert aortic mesoangioblasts, mural pericytes (calcifying vascular cells), or valve myofibroblasts to osteogenic fates. Paracrine signals provided by these molecules mimic the epithelialmesenchymal interactions that induce skeletal development. Vascular expression of pro-osteogenic morphogens is entrained to physiological stimuli that promote calcification. Inflammation, shear, oxidative stress, hyperphosphatemia, and elastinolysis provide stimuli that: (1) promote vascular BMP2/4 signaling and matrix remodeling; and (2) compromise vascular defenses that limit calcium deposition, inhibit osteo/chondrogenic trans-differentiation, and enhance matrix vesicle clearance. In this review, we discuss the biology of vascular calcification. We highlight how aortic fibrofatty tissue expansion (adventitia, valve interstitium), the adventitial-medial vasa, vascular matrix, and matrix vesicle metabolism contribute to the regulation of aortic calcium deposition, with greatest emphasis placed on diabetic vascular disease. Key Words: diabetes Ⅲ vascular calcification Ⅲ Wnt signaling Ⅲ bone morphogenetic proteins Ⅲ oxylipids W ith advanced age, vascular inflammation, hypertension, and certain metabolic disorders, calcium accumulates in the arterial macrovasculature. 1 Calcification of aortic valve leaflets and atherosclerotic plaques have long been recognized as clinically important. 2 However, medial artery calcification (MAC) also portends mortality and amputation risk. 1,[3][4][5] Studies of vascular calcified tissue metabolism significantly lag behind those of skeletal metabolism. Executive cell types familiar to bone biologists are seen in calcifying aortic specimens. 1,6 As in bone, endothelial, mesenchymal, and hematopoietic cell lineages control vascular mineral accumulation, with cellular activities entrained to morphogenetic, metabolic, inflammatory, and mechanical demands placed on each vascular segment. 1 We provide a brief overview of vascular calcification, emphasizing how paracrine osteogenic signals recruited by dysmetabolic insults promote aortic calcium deposition in diabetic vascular disease. We point to emerging evidence that inflammation, mechanical, and metabolic oxidative stresses not only provide stimuli that induce vascular osteogenic morphogens but also compromise defense mechanisms that limit vascular calcium deposition. 1 Aortic MACMAC is a high...

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Isolation of calcifiable vesicles from aortas of rabbits fed with high cholesterol diets

Cited by 37 publications

References 37 publications

Mineral Surface in Calcified Plaque Is Like That of Bone

Mineral Surface in Calcified Plaque Is Like That of Bone

Lipoprotein(a) Enhances Advanced Atherosclerosis and Vascular Calcification in WHHL Transgenic Rabbits Expressing Human Apolipoprotein(a)

Molecular Mechanisms of Vascular Calcification

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