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PubMed2000

Prevention of glutaraldehyde-fixed bioprosthetic heart valve calcification by alcohol pretreatment: further mechanistic studies.

BACKGROUND AND AIM OF THE STUDY: Calcification is a major cause of failure of bioprosthetic heart valves derived from glutaraldehyde-crosslinked bovine pericardium or porcine aortic valve (PAV) cusps. Recently, we have shown that ethanol pretreatment of PAV cusps prevents calcification in animal models. METHODS AND RESULTS: In this study we showed that ethanol pretreatment was equally effective in preventing calcification of glutaraldehyde-crosslinked bovine pericardium (control Ca2+ = 121.16+/-7.49 microg/mg tissue; ethanol-pretreated Ca2+ = 2.95+/-0.78 microg/mg). Furthermore, other low-molecular weight alcohols such as methanol and isopropanol were also effective in mitigating calcification of PAV cusps. Storage of ethanol-pretreated cusps in glutaraldehyde before implantation allowed partial return of calcification, suggesting a role for ethanol-glutaraldehyde interactions in preventing calcification. However, when ethanol-pretreated cusps were stored in ethanolic glutaraldehyde up to one month, the anti-calcification effect of ethanol persisted. The conditions whereby PAV cusps were crosslinked in pure, non-aqueous, alcoholic glutaraldehyde solutions were also examined. The crosslinking was equivalent to the standard aqueous glutaraldehyde crosslinking as indicated by thermal denaturation temperatures (Td) obtained by differential scanning calorimetry (DSC) and resistance to collagenase digestion. However, these cusps had lower water content and showed a marked decrease in spin-lattice relaxation times (T1) obtained by solid-state proton nuclear magnetic resonance (NMR). Moreover, these cusps calcified heavily in the 21-day rat subdermal implants. Thus, alcohol treatment during glutaraldehyde crosslinking was not useful. CONCLUSION: Glutaraldehyde storage after ethanol pretreatment aggravates calcification; moreover, alcoholic-glutaraldehyde crosslinking solutions are not beneficial for anti-calcification. Ethanol pretreatment of glutaraldehyde-pretreated bovine pericardium prevents its calcification.

2-Propanol↗
PubMed1998

Renal ostodystrophy during the developing stage of maintenance dialysis in Transylvania. Early development of periarticular calcifications and beta 2 microglobulin amyloidosis in spite of a relatively good prevention of secondary hyperparathyroidism.

BACKGROUND: Dialysis facilities have been introduced only recently in Transylvania with many limitations, in particular a standard high calcium dialysate, Al(OH)3 as phosphate binder and pharmacological doses of native vitamin D2, but neither CaCO3 nor 1 alpha hydroxylated vitamin D. Rheumatological complaints and metastatic calcifications were frequent, leading to suspect either overt hyperparathyroidism, adynamic bone disease or beta 2 microglobulin amyloidosis. AIMS OF THE STUDY: Evaluate the prevalence of radiological osteitis fibrosa, amyloid osteoarthropathy and periarticular calcification and their link with PTH secretion, phophocalcic disorders, acidosis, bone turn over, aluminum and beta 2 microglobulin accumulation in the dialysis population of Sibiu (Transylvania). METHODS: The clinical and radiological rheumatological data of the 49 uremic patients dialyzed in Sibiu since 1990 were reviewed as well as the monthly routine monitoring of their plasma phosphocalcic parameters. Furthermore in July 1994, 36 of them had an X rays of the hands for evaluation of subperiosteal resorption of the phalanges, periarticular calcifications and carpal cysts as well as a determination of plasma concentrations of intact PTH (normal range: 10-55; optimal range: 100-200 pg/ml), osteocalcin, bone alkaline phosphatase, aluminum and 25 OH vitamin D. RESULTS: The prevalence of subperiostal resorption of the phalanges was 8% and that of severe biological hyperparathyroidism (PTH > 400 pg/ml) 22%, whereas that of a relative hypoparathyroidism (PTH < 100 pg/ml) was 31%. Mean plasma concentrations of calcium was 2.07 +/- 0.15; of phosphate 2.50 +/- 0.35; of bicarbonate 15 +/- 2.0 mmol/l, of 25 OHD 30 +/- 20 ng/ml, of aluminum 1.1 +/- 0.5 mumol/l. Plasma PTH concentrations were negatively correlated to dialysis duration, and to plasma concentrations of aluminum, calcium and 25 OH vitamin D but not to those of phosphate and bicarbonate. Multivariate analysis showed however that only duration of dialysis and plasma aluminum concentration were independently and negatively correlated to plasma PTH concentrations. The prevalence of periarticular calcifications (26%) and of carpal cysts suggestive of beta 2 microglobulin amyloidosis (10%) were relatively high considering the young age of the population (42 years) and the short duration of dialysis (2.6 years). Patients with calcifications comparatively to those without calcifications were older, had longer duration on dialysis, higher prevalence of carpal cysts and higher plasma beta 2 microglobulin concentrations, lower plasma PTH (98 versus 313 pg/ml) and higher plasma aluminum concentration (1.3 versus 0.8 mumol/l). Patients with carpal cysts comparatively to those without cyst were older, had a longer duration on dialysis and a higher prevalence of periarticular calcifications. CONCLUSIONS: a) In spite of no use of 1 alpha hydroxylated vitamin D derivatives, and poor control of hyperphosphatemia and acidosis, hyperparathyroidism declined with duration of dialysis due to the use of a high dialysate calcium concentration, Al(OH)3 as sole phosphate binder and high supplement of native vitamin D. b) Considering the relative young age and short duration on dialysis, the prevalence of periarticular calcifications and carpal cysts were high. c) Calcifications were possibly favored by relative hypoparathyroidism and moderate aluminum overload. d) The association of periarticular calcifications and subchondrial cysts suggest a causal relationship.

Adult↗
PubMed2003

Cavernous carotid artery calcification and white matter ischemia.

BACKGROUND AND PURPOSE: The relevance of cavernous carotid artery calcification on unenhanced CT scans of the brain has recently been investigated against the backdrop of the widespread implementation of coronary artery calcification scoring. We sought to determine whether the degree of cavernous carotid artery calcification correlated with scores of white matter hyperintensity seen on MR images. In so doing, we sought to establish a relative risk for future stroke on the grade of carotid calcification. METHODS: Neuroradiologic findings in 187 patients who underwent CT and MR imaging examinations within 1 month of each other were retrospectively reviewed. The degree of circumferential calcification and thickness of calcification were graded for the cavernous carotid arteries on the basis of CT findings. Using the scale developed by the Cardiovascular Health Study, the white matter was graded for degree of disease on the basis of MR findings. Correlation tests and regression analyses were performed to determine the impact of age, race, and sex on results. RESULTS: Although the cavernous carotid calcification scores and the MR imaging white matter scores showed good correlation (P <.001), the effect was mediated by age. With age factored in as a covariant, no correlation was shown between CT calcification scores and MR imaging white matter scores. Sex had no effect, but African American study participants had worse MR imaging white matter scores than did white participants. CONCLUSION: After adjusting for age, cavernous carotid calcification grades and MR imaging white matter scores do not show a significant correlation. The relative risk for future stroke cannot be predicted from cavernous carotid calcifications.

Adult↗
PubMedDate not supplied

[Can cardiovascular calcifications be prevented in chronic kidney disease?].

Chronic kidney disease, with special regard to hemodialysis patients, develop frequent and widespread cardiac and vascular calcifications. In the heart calcifications are mainly located in the coronary arteries and in the valvular structures. There is a strict relation between cardiovascular mortality in CKD and the extent of cardiac and vascular calcifications. Therefore it is important to evaluate the causes of extraskeletal calcifications for the evaluation of the possibility of prevention. The importance of hyperphosphatemia, of hypercalcemia and of the increased CAxP product as a cause of cardiac calcification has been clearly underlined. However the mechanism of calcification, initially considered a physico-chemical precipitation, has been investigated with the conclusion that the process is mediated by cellular differentiation and production of factors favoring mineralization in the extracellular milieu. Increased serum phosphate levels are able to induce a transformation of vascular smooth muscle cells into osteoblast-like cells, able to produce factors known to be pro-mineralizing agents in the bone tissue. Further studies have revealed the importance of a number of inhibitors of calcification of cardiovascular structures, like Fetuin-A, MGP, Osteopontin, Osteoprotegerin. Therefore at present the calcification process of vascular tissue is considered to be linked to a balance between inducers and inhibitors of calcium-phosphate deposits. Prevention of cardiac calcifications is at present mainly based of optimal control of serum phosphate and reduction of calcium load through the use of non-calcium containing phosphate binders. Treatment with statins for prevention and treatment of atherosclerosis is also an important means of decreasing the size and number of atherosclerotic plaques, where a portion of the calcification process develops.

Calcinosis↗
PubMed1988

Renal calcification incidence in very low birth weight infants.

Serial ultrasound examinations were performed on 31 neonates with birth weights of less than 1,500 g for the detection of renal calcifications. Renal calcifications occurred in 20 (64%) of the infants at a mean age of 39.3 +/- 26.7 days of life. Infants with renal calcifications had shorter gestations (28.2 +/- 1.8 v 31 +/- 1.4 weeks, P less than .004) and lighter birth weights (924 +/- 195 v 1,338 +/- 100 g, P less than .004) than those infants without renal calcifications (n = 11). Furosemide administration was more common in the infants with renal calcifications (65% v 9.1%, P less than .001). The mean total dose of furosemide administered before renal calcifications were noted was 9.59 +/- 7.25 mg/kg. The 20 neonates with renal calcifications had a mean urine calcium level of 12.0 +/- 6.8 mg/kg/24 hours, mean urine calcium to creatinine ratio of 1.32 +/- 1.03 (range 0.3 to 4.45), and a mean alkaline phosphatase concentration of 961 +/- 327 IU. Initial parathyroid hormone levels were not different between the two groups, and subsequent determinations in infants with renal calcifications did not differ significantly from initial values. Renal calcifications are fairly common among very low birth weight infants, particularly in those receiving supplemental calcium and furosemide therapy. Although long-term implications of such findings are not known, close monitoring of renal function by serial determinations of urine calcium and urine calcium to creatinine ratios may identify those infants at risk for renal calcifications.

Calcinosis↗
PubMed1983

Calcific diseases. A concept.

New observations portray calcification processes as similar whether occurring normally or pathologically. Most forms of calcification are initiated by membranous organelles, ie, extracellular, calcifying "matrix vesicles" or intracellular mitochondria. Matrix vesicles promote calcification through calcium-binding phospholipids and phosphatase activity. Mitochondria use a forceful, inwardly directed Ca and phosphate transport mechanism. After mineral initiation, the proliferation of mineral crystals is dependent on regulatory factors, such as extracellular Ca2+ and PO4(3-) and other mineral inhibitors and promoters. Calcific diseases are defined as those in which (1) Ca uptake is early, (2) calcification is importantly related to dysfunction, and (3) the control of calcification may lead to decreased morbidity or enhanced diagnostic capability. Calcific diseases include such well-known entities as crystal deposition arthritis, atherosclerosis, calcific valvular sclerosis, tumor calcification, dental plaque, and dysfunctional calcification occurring in implanted cardiovascular devices.

Arteriosclerosis↗
PubMed1994

Dynamic in vitro calcification of porcine aortic valves.

Previous work in our laboratory has demonstrated a simple, dynamic in vitro calcification method for studying bovine pericardial heart valves. The calcification produced closely resembled that found in clinical explant valves. The current study extends this technique to the porcine aortic bioprosthesis. Five Carpentier-Edwards porcine aortic bioprostheses were calcified in vitro in a modified wear tester. All valves calcified to a similar degree as bovine pericardial valves. Calcification predominated on the ribbed tissue structures near the commissures on the outflow surfaces. The same calcification pattern was seen in clinical explant valves. A number of anti-calcification modifications of porcine aortic valves were also investigated. These had all previously inhibited calcification of bovine pericardium in a rat subdermal implant model but had failed to reduce calcification in whole pericardial valves calcified in vitro under dynamic conditions. The modified porcine valves produced similar results: no modification achieved reduction of calcification on exposure to the functional valve calcification model. The dynamic in vitro calcification test has been shown to be useful for the study of both main types of bioprostheses, bovine pericardial and porcine aortic valves, and for the assessment of alterations to these biomaterials.

Animals↗
PubMed1998

Relations of cigarette smoking and dietary antioxidants with placental calcification.

Associations between maternal cigarette smoking and accelerated placental maturation measured as tissue calcification have been reported. The authors sought to address whether intakes of the dietary antioxidants, vitamin C, alpha-tocopherol, and beta-carotene, were related to placental calcification of the maternal surface and villi in a cohort of smokers and nonsmokers at risk for delivering small-for-gestational age infants. Gross and histologic examination of placentas were used to determine calcification at the surface (n = 1,213) and villus sites (n = 730), respectively, in a prospective study of black and white women who delivered singleton births between December 1985 and October 1988 at the University of Alabama at Birmingham Hospital in Birmingham, Alabama. Controlling for race and gestational age, likelihood of surface and villus calcification increased as smoking levels increased. Significant reductions in villus calcification were related to alpha-tocopherol intake after controlling for smoking and gestation while intakes of beta-carotene and vitamin C were related to significant reductions in calcification for black but not white women. Surface calcification was not found to be related to antioxidant intake. The authors' findings confirm a pathologic relation between smoking and placental calcification and suggest that dietary antioxidants may reduce villus calcification.

Antioxidants↗
PubMed2006

Role of the sodium-dependent phosphate cotransporter, Pit-1, in vascular smooth muscle cell calcification.

Vascular calcification is associated with cardiovascular morbidity and mortality. Hyperphosphatemia is an important contributor to vascular calcification. Our previous studies demonstrated that elevated phosphate induces calcification of smooth muscle cells (SMC) in vitro. Inhibition of phosphate transport by phosphonoformic acid blocked phosphate-induced calcification, implicating sodium-dependent phosphate cotransporters in this process. In the present study, we have investigated the role of the type III sodium-dependent phosphate cotransporter, Pit-1, in SMC calcification in vitro. Human SMC stably expressing Pit-1 small interfering double-stranded RNA (SMC-iRNA) were established using a retroviral system. SMC-iRNA had decreased Pit-1 mRNA and protein levels and sodium-dependent phosphate transport activity compared with the control transduced cells (SMC-CT) (2.9 versus 9.78 nmol/mg protein per 30 minutes, respectively). Furthermore, phosphate-induced SMC calcification was significantly inhibited in SMC-iRNA compared with SMC-CT at all time points examined. Overexpression of Pit-1 restored phosphate uptake and phosphate-induced calcification in Pit-1 deficient cells. Mechanistically, although Pit-1-mediated SMC calcification was not associated with apoptosis or cell-derived vesicles, inhibition of phosphate uptake in Pit-1 knockdown cells blocked the induction of the osteogenic markers Cbfa-1 and osteopontin. Our results indicate that phosphate uptake through Pit-1 is essential for SMC calcification and phenotypic modulation in response to elevated phosphate.

Aorta↗
PubMed1976

Ultrastructural and cytochemical studies on the calcification of the tendon-bone joint.

Ultrastructural and cytochemical studies on developing tendon-bone joints (fibrocartilage) of rats indicated that the initial calcification loci were, as in some other calcifying tissues, matrix vesicles. These membrane-bounded vesicular structures were concentrated in the spaces between the longitudinal cell columns of the fibrocartilage. Where calcification was going to start, the vesicles became denser and more osmiophilic in appearance. The first identifiable needles of apatite crystals were deposited in and close to the matrix vesicles. Where calcification was more extensive and crystals radiating from each calcification center formed a calcified spherule, the matrix vesicles were no longer deposits of minerals was noticed at the site of the initial calcification. Alkaline phosphatase activity was demonstrated in the matrix vesicles as well as in the plasma membrane of fibrocartilage cells, most intensely at the initiating site of calcification. Following potassium pyroantimonate fixation to produce electron opaque deposits of calcium, the deposits were located mainly in the mitochondria and plasma membrane of fibrocartilage cells as well as in matrix vesicles. The closer to the initial site of calcification, the stronger the cells and vesicles reacted. In the area where calcification was in progress, however, calcium was gradually lost from the cell and reversely accumulated in the matrix vesicles. The ultrastructural and cytochemical findings from this study suggested that they were of cellular origin and liberated into the matrix from cells, partly by way of budding off and partly by cell disintegration. The possible roles of matrix vesicles at the initiating sites of calcification in fibrocartilage were discussed.

Alkaline Phosphatase↗
PubMed2006

Light-enhanced calcification and dark decalcification in isolates of the soft coral Cladiella sp. during tissue recovery.

Light-enhanced calcification is a general characteristic of zooxanthellate corals, suggesting a link between calcification by the coral and photosynthesis by the zooxanthellae, but the relationship between zooxanthellae and coral hosts during this process has not been elucidated. We hypothesized that the effects of tissue injury on the coral fragments used in experiments studying calcification might obscure that link. To detect the effects of tissue injury on light-enhanced calcification, we measured calcification rates (sclerite formation) in the soft coral Cladiella sp. by the alkalinity anomaly method during a 36-day experiment following injury associated with coral fragmentation. In the 2 weeks after colony fragmentation, the calcification response did not show a relation with light intensity. The typical light-enhanced calcification pattern was not noticed until day 15 of tissue recovery. The calcification rate of this soft coral increased with light intensity and time of tissue recovery and was comparable to that of hard corals exposed to similar experimental conditions. However, Cladiella sp. decalcified in the dark. The diurnal calcification-decalcification cycles probably control sclerite size and shape.

Animals↗
PubMedDate not supplied

The differences in the chronology and calcification of second molars between angle Class III and Class II occlusions in Japanese children.

The purpose of this study was to examine the differences in the times of eruption and calcification of the permanent dentition between skeletal class III and class II groups. (And also to examine the relationship between the time of eruption and the type of malocclusion) Fifty-three children, ages seven to ten years, were selected. Of these, twenty-six children (twelve boys and fourteen girls) were Angle class III with minus ANB and twenty-seven children (eleven boys and sixteen girls) were Angle class II with five or more ANB. Panoramic radiographs and cephalometric radiographs were used. The panoramic radiographs showed that the calcification of the maxillary second molars in class II were earlier than in class III using Nolla's classification. There was no statistically significant difference, however, for mean values of calcification stages, using Nolla's classification, between boys and girls. The cephalometric and panoramic radiographs showed that the times of eruption and calcification were earlier in the maxillary second molars than in the mandibular second molars for class II. In contrast, the times of eruption and calcification were earlier in the mandibular second molars than in the maxillary second molars for class III. The times of eruption and calcification of the maxillary molars were significantly related to the length of the ANS-PNS. The longer the ANS-PNS, the earlier were the times of eruption and calcification. There was a significant relationship between the ANB angle and the time of eruption, as well as the ANB angle and calcification. The larger ANB had earlier calcification and chronology of maxillary second molars.

Cephalometry↗
PubMed1998

Calcification in atherosclerotic plaque of human carotid arteries: associations with mast cells and macrophages.

Calcification has been examined in 250 samples of atherosclerotic lesions (types II to VI) of human carotid arteries using von Kossa and haematoxylin staining. Early calcification described as 'stippling' was first noted in stage III specimens, with intermediate and solid calcifications becoming increasingly prominent within advanced plaques, especially stages Vb and VI. Although the relative frequencies of stippling, intermediate and large calcified deposits varied between plaques of the same stage, the prevalent sites of calcification were recognized as the deeper regions of the intima and the atheroma. Immunolocalization and histochemical techniques were used to identify the associations of mast cells (MCs), macrophages, smooth muscle cells (SMCs), and elastin with the different stages of calcification. Early, dispersed stippling was commonly associated with local accumulations of macrophages (HAM56 and CD68-positive), MCs and extracellular MC tryptase, the presence of immunoreactive elastin, but the relative absence of SMCs. Intermediate stages of calcification described as 'morula' deposits were also associated with local increases in the numbers of macrophages and MCs. Larger calcified deposits, even within the same plaque specimen, showed no regular pattern of cellular or elastin associations. However, in the vast majority of specimens, macrophages represented the predominant cell type associated with different phases of calcification. By contrast, the calcification less frequently observed in the media beneath advanced plaques was commonly associated with SMCs and elastin; only rarely were macrophages or MCs present. These studies are the first to demonstrate that macrophages, MCs, and extracellular tryptase frequently occupy micro-environmental loci showing the first stages of calcification within the atherosclerotic plaque; similar associations with more advanced mineral deposits are discussed in relation to plaque rupture.

Aged↗
PubMed1996

Calcification of polyurethanes implanted subdermally in rats is enhanced by calciphylaxis.

Calcification complicates the use of the polymer polyurethane in cardiovascular implants. To date only costly experimental circulatory animal models have been useful for investigating this disease process. In this paper we report that polyurethane calcification in rat subdermal implants is enhanced by overdosing with a vitamin-D analog. The calcification-prone state, known as calciphylaxis, was induced in 4-week old rats by oral administration of a vitamin-D analog, dihydrotachysterol. We studied two commercially available polyurethanes (Biomer and Mitrathane) and two proprietary polyurethanes (PEU-2000 and PEU-100). PEU-100 is unique because it is derivatized with ethanehydroxy-bisphosphonate (EHBP) for calcification resistance. Polyurethane calcium and phosphate levels and morphological changes due to calciphylaxis were compared with those of control rat subdermal explants in 60-day studies. Increased polyurethane mineralization was observed due to calciphylaxis with 60-day rat subdermal explants of Biomer, Mitrathane, and PEU-2000 (calcium levels, respectively, 4.13 +/- 0.56, 18.61 +/- 2.73, and 3.37 +/- 0.22 microgram/mg, mean +/- standard error) as compared to control explants (calcium levels, respectively, 1.22 +/- 0.1, 12.57 +/- 0.86, and 0.20 +/- 0.86 microgram/mg). The study also demonstrated that with 60-day implants calciphylaxis had no side effects on somatic growth and serum calcium levels. Explant surface morphology of these polyurethane explants examined by scanning electron microscopy, back scattering electron imaging coupled with energy dispersive X-ray spectroscopy, and light microscopy demonstrated the presence of predominantly surface-oriented calcification. PEU-100, derivatized with 100 n.moles/ mg of EHBP, resisted calcification with explant calcium levels 0.51 +/- 0.01 (calciphylaxis) and 0.38 +/- 0.01 (control) microgram/mg. It is concluded that calciphylaxis enhances superficial polyurethane calcification in rat subdermal implants and that an EHBP-modified polyurethane resists calcification despite calciphylaxis. Rat subdermal implants using calciphylaxis may be generally useful for evaluating the calcification potential of various biomedical polymers.

Animals↗
PubMed1997

Differential calcification of cusps and aortic wall of failed stented porcine bioprosthetic valves.

In this study, we examined separately calcification of cusps (C) and associated aortic wall (AW) of 38 (13 aortic and 25 mitral) porcine bioprosthetic heart valves explanted from 37 patients (ages 25-80 years, mean 59) for structural dysfunction, following 54-210 months (mean 125 months aortic, 119 months mitral). Valves were sectioned into C and corresponding AW components; calcification was assessed by atomic absorption spectroscopy for calcium and histologic examination. Overall, AW calcification was half that of C (33.3 +/- 5.4 vs. 65.9 +/- 6.3 microg/mg, mean +/- standard error of the mean respectively, p = 0.002). Correlation of calcification in individual C/AW pairs was weak (r2 = 0.34). Calcification in C was nodular, largely in the valve fibrosa, but AW calcification predominated in the cells between elastic lamellae; large nodules were sparse. We conclude that since AW calcification in these failed porcine valves was neither prominent nor clinically significant, this process should rarely if ever be a limiting factor in the function of stented porcine valves, and that development of anticalcification therapies directed toward the AW of stented valves should be of low priority. However, in stent-free valves, the AW is not covered by prosthetic material, and the level of calcification could be greater and more likely to cause clinical problems through stiffening, embolism, and/or protrusion into the lumen of calcific masses.

Adult↗
PubMed1998

Inhibition of aortic wall calcification in bioprosthetic heart valves by ethanol pretreatment: biochemical and biophysical mechanisms.

The effectiveness of ethanol pretreatment on preventing calcification of glutaraldehyde-fixed porcine aortic bioprosthetic heart valve (BPHV) cusps was previously demonstrated, and the mechanism of action of ethanol was attributed in part to both lipid removal and a specific collagen conformational change. In the present work, the effect of ethanol pretreatment on BPHV aortic wall calcification was investigated using both rat subdermal and sheep circulatory implants. Ethanol pretreatment significantly inhibited calcification of BPHV aortic wall, but with less than complete inhibition. The maximum inhibition of calcification of BPHV aortic wall was achieved using an 80% ethanol pretreatment; calcium levels were 71.80+/-8.45 microg/mg with 80% ethanol pretreatment compared to the control calcium level of 129.90+/-7.24 microg/mg (p = 0.001). Increasing the duration of ethanol exposure did not significantly improve the inhibitory effect of ethanol on aortic wall calcification. In the sheep circulatory implants, ethanol pretreatment partly prevented BPHV aortic wall calcification with a calcium level of 28.02+/-4.42 microg/mg compared to the control calcium level of 56.35+/-6.14 microg/mg (p = 0.004). Infrared spectroscopy (ATR-FTIR) studies of ethanol-pretreated BPHV aortic wall (vs. control) demonstrated a significant change in protein structure due to ethanol pretreatment. The water content of the aortic wall tissue and the spin-lattice relaxation times (T1) as assessed by proton nuclear magnetic resonance spectroscopy did not change significantly owing to ethanol pretreatment. The optimum condition of 80% ethanol pretreatment almost completely extracted both phospholipids and cholesterol from the aortic wall; despite this, significant calcification occurred. In conclusion, these results clearly demonstrate that ethanol pretreatment is significantly but only partially effective for inhibition of calcification of BPHV aortic wall and this effect may be due in part to lipid extraction and protein structure changes caused by ethanol. It is hypothesized that ethanol pretreatment may be of benefit for preventing bioprosthetic aortic wall calcification only in synergistic combination with another agent.

Animals↗
PubMed2001

Up-regulated expression of the phosphodiesterase nucleotide pyrophosphatase family member PC-1 is a marker and pathogenic factor for knee meniscal cartilage matrix calcification.

OBJECTIVE: Elevated cartilage inorganic pyrophosphate (PPi) production and PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity are strongly linked with aging-related cartilage calcification in meniscal and articular cartilages. We hypothesized that there were divergent relationships of 3 NTPPPH isozymes with cartilage matrix calcification and sought to identify them. METHODS: We studied knee medial meniscal expression in situ of 3 NTPPPH isozymes of the phosphodiesterase nucleotide pyrophosphatase (PDNP) family: plasma cell membrane glycoprotein 1 (PC-1, or PDNP1), autotaxin (ATX, or PDNP2), and B10/PDNP3. We also used complementary DNA transfection to assess differential functions in matrix calcification of each NTPPPH isozyme in vitro in meniscal cells. RESULTS: We observed diffuse cell-associated ATX and B10/PDNP3 expression in central (chondrocytic) and, to a lesser degree, peripheral (fibroblastic) regions of normal, degenerative uncalcified, and degenerative calcified menisci. In contrast, PC-1 expression was only robust at sites of apoptotic cells and calcification in central regions of degenerative menisci. Only PC-1 was abundant at the perimeter of meniscal cells and in association with meniscal cell-derived matrix vesicles (MVs). Because each PDNP-family isozyme was expressed by cells near calcifications, we transfected the isozymes in nonadherent knee meniscal cells cultured with ascorbic acid, beta-glycerophosphate, and dexamethasone supplementation to stimulate them to calcify the matrix. PC-1, but not ATX or B10/PDNP3, consistently promoted increased MV NTPPPH, MV-associated PPi, and extracellular PPi. PC-1 also increased matrix calcification (with hydroxyapatite crystals) by meniscal cells. ATX uniquely induced alkaline phosphatase activity, but promoted only moderately increased matrix calcification. CONCLUSION: We identified divergent effects of 3 PDNP-family NTPPPH isozymes on meniscal cell matrix calcification. Increased expression of PC-1 is both a marker and a potential pathogenic factor for knee meniscal cartilage matrix calcification.

Aging↗
PubMed2002

The involvement of matrix glycoproteins in vascular calcification and fibrosis: an immunohistochemical study.

Calcification and fibrointimal proliferation are associated with advanced complicated atherosclerosis in large arteries but may also occur in smaller vessels, resulting in ischaemic tissue necrosis. This study investigates whether the mechanisms of calcification and intimal fibrosis are similar in vessels of different sizes. The localization of osteopontin (OPN), matrix Gla protein (MGP), thrombospondin-1 (TSP-1), and cartilage oligomeric matrix protein (COMP) was investigated in three types of human vascular lesions: atherosclerosis, chronic vascular rejection (CVR) in renal allografts, and calcific uraemic arteriolopathy (calciphylaxis). These lesions were chosen as they affect different sized blood vessels and they exhibit a fibroproliferative intimal reaction, with or without calcification, resulting in luminal obliteration and ischaemic complications. OPN, MGP, TSP-1, and COMP were not detected in normal blood vessels. However, OPN and MGP were expressed at sites of calcification within atherosclerotic lesions and in microvessels in calciphylaxis, suggesting that calcification in different sized vessels may occur by a common mechanism. These proteins were not detected in areas of fibrointimal proliferation. In contrast, TSP-1 was localized primarily within the fibrous tissue of atherosclerotic lesions and was also expressed in the expanded fibrous intima of arteries showing CVR. COMP was localized primarily within the fibrous tissue under the lipid core of the majority of advanced atherosclerotic lesions. TSP-1 and COMP were also detected in areas of microcalcification in atherosclerotic lesions and TSP-1 was detected adjacent to areas of calcification in calciphylaxis. However, neither TSP-1 nor COMP was localized to calcific foci within these lesions. The localization of OPN, MGP, TSP-1, and COMP to pathological, but not normal arterial intima supports a pathogenetic role for these proteins in the development of vascular fibrosis and calcification. Modulation of their production and activity may offer a novel approach to the therapy of a number of vascular diseases.

Adult↗