Vascular Calcification Mechanisms

Giachelli, Cecilia M.

doi:10.1097/01.asn.0000145894.57533.c4

Cited by 493 publications

(436 citation statements)

References 60 publications

(50 reference statements)

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“…According to the data available (Poloni and Ward 2014), the unwanted depositions could consist of many substances and all of them always lead to various diseases. Regarding the unwanted depositions of CaPO 4 , they are found in soft tissue calcification (in damaged joints, blood vessels, dysfunctional areas in the brain, diseased organs, scleroderma, prostate stones) (Reid and Andersen 1993;Scotchford and Ali 1995;P'ng et al 2008;Brancaccio and Cozzolino 2005;Goff and Reichard 2006;Bittmann et al 2003;Molloy and McCarthy 2006;Giachelli 2004;Kazama et al 2007), kidney (Giannossi and Summa 2012;Mukherjee 2014) and urinary (Zhu et al 2014;Huo et al 2015;Selvaraju et al 2015) stones, dental pulp stones and dental calculus (Kakei et al 2009;Kodaka et al 1988Kodaka et al , 1998Ç iftçioglu et al 1998;Hayashizaki et al 2008), salivary stones (Zelentsov et al 2001;Luers et al 2014), gall stones (Qiao et al 2013;Hussain and AlJashamy 2013), pineal gland calcifications (Güney et al 2013), atherosclerotic arteries and veins (Ortlepp et al 2004;Tomazic 2001;Marra et al 2006;Kurabayashi 2013), coronary calcification (Fitzpatrick et al 2003;Matsui et al 2015), damaged cardiac valves (Suvorova and Buffat 2005), calcification on artificial heart valves (Giachelli 2001; Pettenazzo et al 2001;...…”

Section: Antlersmentioning

confidence: 99%

Calcium orthophosphates (CaPO 4 ): Occurrence and properties

Dorozhkin¹

2017

Morphologie

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Section: Antlersmentioning

confidence: 99%

Calcium orthophosphates (CaPO 4 ): Occurrence and properties

Dorozhkin¹

2017

Morphologie

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“…Towler and colleagues have recently proposed a major role for BMP2-Msx2-Wnt signaling pathway in arterial medial calcification using Msx2 transgenic mice (17). To assess the possible involvement of Abcc6 with this and other likely calcification mechanisms, we assembled a list of candidate genes for arterial calcification from the literature (18)(19)(20) and performed correlation analyses between their expression levels and that of Abcc6 using the BxD and BxH microarray data sets. In genetic crosses, transcript levels are subjected to hundreds of genetic perturbations, and genes in common pathways tend to exhibit coexpression (21).…”

Section: Abcc6 Is Coregulated With Local Calcification Regulatory Genmentioning

confidence: 99%

Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics

Meng

Vera²,

Che³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

119

130

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The genetic factors contributing to the complex disorder of myocardial calcification are largely unknown. Using a mouse model, we fine-mapped the major locus (Dyscalc1) contributing to the dystrophic cardiac calcification (DCC) to an 840-kb interval containing 38 genes. We then identified the causal gene by using an approach integrating genetic segregation and expression array analyses to identify, on a global scale, cis-acting DNA variations that perturb gene expression. By studying two intercrosses, in which the DCC trait segregates, a single candidate gene (encoding the ATPbinding cassette transporter ABCC6) was identified. Transgenic complementation confirmed Abcc6 as the underlying causal gene for Dyscalc1. We demonstrate that in the cross, the expression of Abcc6 is highly correlated with the local mineralization regulatory system and the BMP2-Wnt signaling pathway known to be involved in the systemic regulation of calcification, suggesting potential pathways for the action of Abcc6 in DCC. Our results demonstrate the power of the integrative genomics in discovering causal genes and pathways underlying complex traits.expression quantitative trait locus ͉ transgenic ͉ positional cloning ͉ osteopontin C haracterized by hydroxyapatite deposition in necrotic myocytes, myocardial calcification is common in specific forms of cardiomyopathy and in myocardial infarction. It has been estimated that Ϸ8% of patients with severe myocardial infarction develop myocardial calcification within 6 years, suggesting a genetic predisposition for postinjury healing and remodeling processes (1). Historically, dystrophic cardiac calcification (DCC) has been considered a spontaneous form of cardiomyopathy in mice, associated with a variety of predisposing factors, but with normal blood levels of calcium and phosphate. Experimentally, it can be reproducibly initiated using a transdiaphragmal freeze-thaw injury or a high-phosphorous (HP) diet (2, 3). Several inbred mouse strains, including C3H/HeJ (C3H) and DBA/2J (DBA), are highly susceptible, whereas many other inbred mouse strains, including C57BL/6J (B6), C57BL/10J (B10), A/J, MRL/MpJ, and BALB/cJ are resistant (refs. 4 and 5; X.W., T.A.D., and A.J.L., unpublished data). In DCC susceptible strains, calcification has also been observed in skeletal muscle, including in the tongue and diaphragm, and kidney, suggesting a systemic defect (2, 5).Using quantitative trait locus (QTL) analysis of an F 2 intercross between B6 and C3H mice (BxH), we previously mapped four DCC loci (6, 7). The locus on chromosome 7 (Dyscalc1), which exhibits recessive inheritance, explains 31% of the total genetic variance and is the major contributor. Dyscalc1 was confirmed by separate intercrosses of B6 and DBA mice (BxD) (5, 8). The C3H strain was originally derived from an outbreeding experiment of the DBA strain, leading us to hypothesize that the susceptible strains C3H and DBA share a common diseasecausing allele (8). To fine map the Dyscalc1 locus, we screened a panel of recombinant congenic (RC) s...

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“…V ascular calcification, a widely recognized and common complication of chronic kidney disease (CKD), increases the risk for cardiovascular morbidity and mortality (1,2). Although the causes of vascular calcification in CKD remain to be elucidated, associated risk factors include age, hypertension, time on dialysis, and abnormalities in calcium (Ca) and phosphorus (P) metabolism, resulting in a raised serum Ca-P product (Ca ϫ P) (3,4).…”

mentioning

confidence: 99%

Calcimimetic R-568 Decreases Extraosseous Calcifications in Uremic Rats Treated with Calcitriol

López¹,

Aguilera–Tejero²,

Mendoza³

et al. 2006

Journal of the American Society of Nephrology

138

111

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Calcimimetics decrease parathyroid hormone (PTH) levels in uremic patients with secondary hyperparathyroidism without increasing serum calcium (Ca). The aim of this study was to evaluate the effect of calcimimetic R-568 alone or in combination with calcitriol on vascular and other soft tissue calcifications in uremic rats with secondary hyperparathyroidism. Shamoperated and 5/6 nephrectomized Wistar rats were studied. 5/6 Nephrectomized rats were treated with vehicle, calcitriol (80 ng/kg every other day), R-568 (1.5 and 3 mg/kg per d), and both calcitriol and R-568 1.5 mg/kg, as above. Rats were killed after 14 or 56 d of treatment. Blood was drawn for biochemical measurements. Aortic, heart, kidney, lung, and stomach tissue samples were processed for histopathology and measurement of tissue Ca and phosphorus content. PTH concentrations were significantly reduced by all treatments. Treatment with calcitriol induced significant vascular calcification (aortic Ca increased to 4.2 ؎ 1.2 mg/g at day 14 and to 11.4 ؎ 0.7 mg/g at day 56; P < 0.05 versus vehicle). Treatment with R-568 did not induce vascular calcification. Concurrent administration of R-568 with calcitriol reduced the aortic Ca (1.9 ؎ 0.2 mg/g at day 14 and 7.5 ؎ 1.4 mg/g at day 56) in relation to calcitriol alone. Soft tissue calcifications mirrored aortic mineralizations. Survival was significantly (P < 0.001) reduced in calcitriol-treated rats, and mortality was attenuated (P ‫؍‬ 0.01) by concurrent treatment with R-568. In uremic rats, R-568 reduces elevated PTH levels without inducing vascular calcification, prevents calcitriol-induced vascular calcification, and decreases mortality.

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Vascular Calcification Mechanisms

Cited by 493 publications

References 60 publications

Calcium orthophosphates (CaPO 4 ): Occurrence and properties

Calcium orthophosphates (CaPO 4 ): Occurrence and properties

Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics

Calcimimetic R-568 Decreases Extraosseous Calcifications in Uremic Rats Treated with Calcitriol

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