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Biomedical subjects

G Wolf

Publications and source records attributed to G Wolf.

At least 73 records · Page 4Linked to original sources
PubMed2001

Chromosomal abnormalities in the first and second polar body.

Aneuploidy free oocytes may be pre-selected by testing the first and second polar bodies removed from oocytes following their maturation and fertilization. We present here our experience on the application of the method in IVF cycles from patients of advanced maternal age. Overall, 5590 oocytes were obtained from 917 cycles and tested by polar body sampling and fluorescent in situ hybridization (FISH) analysis using specific probes for chromosomes 13,16,18,21 and 22. FISH results were available in 4599 (82.2%) of 5590 oocytes studied, from which 2077(45.2%) were with aneuploidies. Thirty six point one percent of aneuploidies were of the first meiotic origin, and 29.3% of the second meiotic origin. Most errors in the first meiotic division were represented by chromatid errors. The transfer of embryos deriving from 2014 of 2520 aneuploidy free oocytes in 821 treatment cycles resulted in 182 (22.2%) clinical pregnancies and 140 healthy children born after confirmation of the polar body diagnosis. Polar body testing of oocytes provides an approach for pre-selection of aneuploidy free embryos, improving pregnancy rate in IVF patents of advanced maternal age.

Adult↗
PubMed2001

Astrocytes induce manganese superoxide dismutase in brain capillary endothelial cells.

Astrocytes induce blood-brain barrier (BBB) properties in brain endothelial cells (EC)*O(2)*, generated in blood and EC, opens the BBB. Hence, high activity of superoxide dismutase (SOD) is a prerequisite for normal BBB function. Therefore, the influence of rat astrocytes on the expression of manganese (Mn)SOD in rat EC was investigated in two coculture models of the BBB, allowing either exchange of soluble factors or additionally cellular contacts. Activity, protein content and mRNA expression of endothelial MnSOD were significantly increased in both coculture models in comparison to monoculture by soluble astrocytic factors, such as cytokines. High activity of endothelial MnSOD may be considered as a further essential property of the BBB, which is induced and maintained by astrocytes.

Animals↗
PubMed2001

First experience with a new dedicated ultrasound system for computer-guided large-core breast biopsy.

We describe a new dedicated ultrasound system for computer-guided large core breast biopsy (LCBB) and report our first clinical experience in 45 female patients. After an initial 30 biopsy procedures on a US breast phantom, LCBB using this new system was performed in 45 non-palpable surgically verified breast lesions. All biopsies were performed by the same radiologist using 14-gauge long-throw biopsy needles. Histological results following LCBB were compared with open surgical biopsy. Procedure time and any complication arising was registered in all procedures. Biopsies using this prototype were successful and yielded sufficient material in all 45 lesions. There were 23 benign and 22 malignant lesions with complete histological agreement between LCBB and open surgical biopsy in 44 of the 45 lesions. In one invasive ductal cancer the pathologist could only state high probability of malignancy but not give a definite diagnosis. Besides one case with early termination due to decreased visibility of the target lesion, no technical complications were noted. Slight vasovagal reactions were seen in 4 patients but did not alter the histological results. The average procedure time was 30+/-2.7 min. This new dedicated US system for computer-guided LCBB is an accurate and safe method for diagnosing breast lesions. Although this new system may have no major impact for US-guided LCBB experienced physicians, it might be a promising alternative for the non-skilled physician to currently available breast biopsy techniques.

Adult↗
PubMed2001

Altered laminar distribution of hippocampal zinc in mutant mice lacking neuronal nitric oxide synthase. A histochemical study.

The recently discovered role of nitric oxide (NO) in the accumulation of zinc in the central nervous system encouraged us to compare the distribution of zinc in the hippocampal formation and other brain regions of nitric oxide synthase knockout with wild-type mice. The histochemical Timm's staining technique was used. While no changes in the patterns of zinc staining were observed in extrahippocampal brain areas, lamina-specific differences appeared in the distribution of the metal in hippocampi of normal and mutant mice. Less Timm's stainable zinc was detected in the neuropil of strata oriens and radiatum and a loss of Timm's-stained infrapyramidal fibers in knockout mice. The hilar region as well as the suprapyramidal and intrapyramidal blades of the mossy fiber system did not differ between mutant and wild-type mice. Our data show that life-long withdrawal of neuronal-derived NO has effects on the accumulation of zinc in the hippocampal formation of mice.

Animals↗
PubMed2001

Protective effect of XY99-5038 on hydrogen peroxide induced cell death in cultured retinal neurons.

XY99-5038 is a preparation from a specific formula provided by Dr. Yan Xin, a renowned Traditional Chinese Medicine specialist. This formulation has proven to be effective without side effects but has not been studied under rigorous laboratory conditions. In order to investigate the role of XY99-5038 in protecting neurons from degeneration, we used retinal neuronal culture as a model system to study the protective effects of XY99-5038 against hydrogen peroxide (H2O2) induced cytotoxicity. Basic fibroblast growth factor (bFGF), a potent neurotrophic factor, was employed as comparable agent. Retinas of 0-2 days old Sprague-Dawley rats were isolated, dissociated, and the neurons maintained for 2 weeks in a synthetic serum-free media. Cytotoxicity was determined by MTT (3,(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide) and LDH (Lactate dehydrogenase) assays, whereas apoptotic cell death was evaluated by the TUNEL (TdT-mediated digoxigenin-dUTP nick-end labeling) assay. Treatment with H2O2 significantly induced death of retinal neurons. Pretreatment with XY99-5038 prior to insult greatly inhibited or attenuated H2O2 induced cytotoxicity and apoptosis. These effects were shown to be dose-dependent. Our data also show that the protective effect of XY99-5038 is more potent than that of bFGF. Our data suggest that XY99-5038 could be a potential agent in the treatment of disorders associated with oxidative damage.

Animals↗
PubMed2001

[Hypertensive disorders in pregnancy].

BACKGROUND: Hypertensive complications contribute to maternal and fetal morbidity. Hypertensive diseases in pregnancy comprise various disorder from transient hypertension to the dangerous preeclampsia/eclampsia. Diagnosis of these diseases requires an understanding of the normal physiological adaptations during pregnancy. PATHOGENESIS: The primary cause of preeclampsia/eclampsia is a disturbed growth of throphoblast cells, probably induced by an altered maternal immunotolerance. The consequence is a dysfunction of endothelial cells with a decrease in perfusion of the uterus and placenta. The normal balance between vasoconstrictors and vasodilators is changed in favor of vasoconstrictors. Complex changes in the renin-angiotensin system have been detected resulting in an increased angiotensin II-mediated vasoconstriction. The reduction in perfusion of the uterus and placenta eventually leads to preeclampsia/eclampsia and growth retardation of the fetus. Manifest preeclampsia/eclampsia is characterized by disturbed microcirculation of target organs such as brain, liver and kidney. An involvement of the liver causes the HELLP syndrome. THERAPY: Various pharmacological approaches to prevent preeclampsia/eclampsia showed disappointing results, but patients with a risk for the eventual development of preeclampsia/eclampsia should be identified, closely monitored, and hypertension should be treated. A systolic blood pressure > 170 mm Hg and diastolic blood pressure > 100 mm Hg should be treated. Drugs such as alpha-methyldopa and dihydralazine that are well-characterized in their fetal effects are the primary choice for the treatment of hypertension in pregnancy. ACE-inhibitors and angiotensin II receptor antagonists are absolutely, diuretics are relatively contraindicated. The causal therapy for preeclampsia/eclampsia is delivery. Gravida before the 33th week of pregnancy should be admitted, hypertension should be treated, and the fetus should be monitored by duplex ultrasound and cardiotocography. New data suggest that early treatment with glucocorticoids may prevent the manifestation of HELLP syndrome. Hypertensive pregnant patients should be treated in tertiary centers with an interdisciplinary approach involving obstetricians, neonatologists, and nephrologists.

Adult↗
PubMed2001

Two-dimensional fluorometry coupled with artificial neural networks: a novel method for on-line monitoring of complex biological processes.

The use of two-dimensional scanning fluorometry as an on-line, noninvasive, in situ bioreactor monitoring technique is extended to complex bioprocesses using mixed cultures, with particular attention to biofilm systems. Using the example of spectra subtraction, it is demonstrated that established methods for fluorescence data analysis have a limited capability of utilizing overall fluorometric information. Artificial neural networks (ANNs) are introduced as a novel nonlinear and nonmechanistic technique for interpreting the highly complex fluorescence maps. It is shown that ANNs are able to infer process performance parameters in a pattern recognition approach, based on the entire fluorescence "fingerprint" of the biological system. The studies were carried out using an extractive membrane bioreactor (EMB) for the degradation of chlorinated organic compounds, operating with mixed cultures. Model pollutants em- ployed were 1,2-dichloroethane, 3-chloro-4-methylaniline, and p-toluidine.

Biodegradation, Environmental↗
PubMed2001

Antioxidant treatment induces transcription and expression of transforming growth factor beta in cultured renal proximal tubular cells.

Transforming growth factor beta (TGF-beta) plays an important role in the development of tubulointerstitial fibrosis in chronic renal disease. We were interested whether interference with oxygen radicals may modulate TGF-beta expression. Unexpectedly, we discovered that diphenylene iodine (DIP), an inhibitor of NADP(H) oxidase, induces a robust increase in TGF-beta transcript expression in cultured mouse proximal tubular cells (MCT cells). A similar increase was seen with EUK-8, a synthetic salen-manganese complex with high oxyradical scavenger activities. This induction of TGF-beta1 mRNA was paralleled by increasing protein expression. Transient transfection of MCT cells with a reporter construct in which murine TGF-beta1 enhancer/promoter elements were cloned in front of the luciferase gene, revealed that DIP, EUK-8, and Tiron all stimulated transcription of the TGF-beta1 gene whereas exogenous H2O2 suppressed transcription. Antisense oligonucleotides against p22phox, but not sense oligonucleotides, also increased transcriptional activity of TGF-beta1. Mutagenesis of Sp1 binding sites in the mouse TGF-beta1 enhancer/promoter abolished the stimulatory effect of the antioxidants. Gel shift experiments revealed that DIP as well as EUK-8 activated binding of nuclear proteins to Sp1 consensus sequence. Our data provide evidence that TGF-beta1 transcription is negatively regulated in MCT cells under basal conditions by NADP(H) oxidase-mediated oxygen radicals. Thus, antioxidant therapy may increase local synthesis of TGF-beta1 in the tubulointerstitium.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed2001

Protection of primary glial cells by grape seed proanthocyanidin extract against nitrosative/oxidative stress.

Previous studies showed that proanthocyanidins provide potent protection against oxidative stress. Here we investigate the effects of grape seed proanthocyanidin extract (GSPE) as a novel natural antioxidant on the generation and fate of nitric oxide (NO) in rat primary glial cell cultures. GSPE treatment (50 mg/L) increased NO production (measured by NO(2-) assay) by stimulation of the inducible isoform of NOS. However, GSPE failed to affect the LPS/IFN-gamma-induced NO production or iNOS expression. Similar responses were found in the murine macrophage cell line RAW264.7. GSPE did not show any effect on dihydrodichlorofluorescein fluorescence (ROS marker with high sensitivity toward peroxynitrite) either in control or in LPS/IFN-gamma-induced glial cultures even in the presence of a superoxide generator (PMA). GSPE treatment alone had no effect on the basal glutathione (GSH) status in glial cultures. Whereas the microglial GSH level declined sharply after LPS/IFN-gamma treatment, the endogenous GSH pool was protected when such cultures were treated additionally with GSPE, although NO levels did not change. Glial cultures pretreated with GSPE showed higher tolerance toward application of hydrogen peroxide (H(2)O(2)) and tert-butylhydroperoxide. Furthermore, GSPE-pretreated glial cultures showed improved viability after H(2)O(2)-induced oxidative stress demonstrated by reduction in lactate dehydrogenase release or propidium iodide staining. We showed that, in addition to its antioxidative property, GSPE enhances low-level production of intracellular NO in primary rat astroglial cultures. Furthermore, GSPE pretreatment protects the microglial GSH pool during high output NO production and results in an elevation of the H(2)O(2) tolerance in astroglial cells.

Animals↗
PubMed2001

Angiotensin II induces p27(Kip1) expression in renal tubules in vivo: role of reactive oxygen species.

Previous studies have demonstrated that angiotensin II (ANG II) mediates cell cycle arrest of cultured renal tubular cells by induction of p27(Kip1), an inhibitor of cyclin-dependent kinases. However, it is not known whether ANG II exerts similar effects in vivo. Infusion of ANG II into naive rats for 7 days increased formation of reactive oxygen species in tubular cells of the kidney. Furthermore, ANG II infusion stimulated protein expression of p27(Kip1) as detected by western blotting of tubular lysates and immunohistochemistry. Infusion of ANG II reduced tubular proliferation as detected by proliferating-cell nuclear antigen (PCNA) immunohistochemistry. The increase in p27(Kip1) expression was not due to an increase in mRNA. Immunoprecipitation experiments revealed that the increased p27(Kip1) protein associates with cyclin-dependent kinase 2. Coadministration of the radical scavenger dimethylthiourea abolished this ANG II mediated p27(Kip1) expression without reducing systemic blood pressure. Furthermore, dimethylthiourea infusion attenuates the ANG II mediated G(1)-phase arrest of tubular cells. However, infusion of norepinephrine did not induce reactive oxygen species or p27(Kip1) expression, despite a significant increase in blood pressure. Thus ANG II induces p27(Kip1) expression in renal tubular cells in vivo. This effect is mediated by reactive oxygen species. Since tubular hypertrophy depends on G(1)-phase arrest and may promote subsequent development of interstitial fibrosis, administering oxygen radical scavenger may be a therapeutic tool to counteract ANG II dependent remodeling of renal tubular cells.

Angiotensin II↗
PubMed2001

Immunocytochemical distribution of nitric oxide synthase in the human corpus cavernosum: an electron microscopical study using the tyramide signal amplification technique.

Nitric oxide has proven to be an important mediator in the relaxation of human cavernosal smooth muscle. Nevertheless, there are many inconsistencies in the literature regarding the cellular and subcellular distribution of endothelial nitric oxide synthase in the human penis. The purpose of this study was to reexamine the localization of eNOS and nNOS in the cellular anatomy of the human cavernous body by means of electron microscopical immunocytochemistry in combination with the tyramide signal amplification technique (TSA). Using specific antibodies against eNOS and nNOS, the NAPDH-diaphorase reaction and advanced protocols for fixation and staining procederes, the occurrence of NOS isoenzymes eNOS and nNOS were examined in cavernosal specimens of ten male patients who were subjected to surgery for penile deviation. eNOS immunoreactivity and NADPH-d staining was seen to be significantly present in the endothelial cells covering the cavernous spaces and in the endothelium of helicine arteries. In endothelial cells, the NADPH-d reaction product BSPT-formazan was abundantly detectable attached to membranes of the endoplasmatic reticulum and the mitochondria whereas posititve eNOS immunostaining was seen in the endothelial cells throughout their cytoplasm without any particular relation to organelles. No considerable eNOS immunoreactivity was detectable in the trabecular smooth muscle cells. nNOS staining was found in nerve fibers innervating the cavernous body and cavernosal arteries. Our results counteract the hypothesis of the cavernous smooth muscle as a local source of NO and underline the importance of an intact endothelial function for penile erection and the contribution of eNOS to this process.

Biotin↗
PubMed2001

[Laser-assisted transcanalicular dacryocystorhinostomy. Initial results].

BACKGROUND: Endoscopes for direct examination of the mucosa and disorders of the lacrimal drainage system have been available for four years. This had led to the wish to be able to treat lacrimal disorders by endoscopes and laser. PATIENTS AND METHODS: Since September 1997 we have treated 48 patients by laser-assisted transcanalicular dacryocystorhinostomy (DCR) using a KTP laser, including all those with stenosis to the nasolacrimal duct and all those with postsaccal stenosis. A bony window with diameter of 5 x 5 mm was created. Bicanalicular intubation into the nose was performed and was left for 3-6 months. RESULTS: We found 40 patients to have patent lacrimal pathway and no symptoms, 4 watering in cold weather, and 4 a restenosis. CONCLUSIONS: The KTP-laser is sufficiently powerful to create bony windows at least 5 mm in diameter, and a transcanalicular laser-assisted DCR is therefore possible.

Dacryocystorhinostomy↗
PubMed2001

High glucose-induced hypertrophy of mesangial cells requires p27(Kip1), an inhibitor of cyclin-dependent kinases.

Hypertrophy of mesangial cells is one of the earliest morphological alterations in the kidney after the onset of diabetes mellitus. We have previously shown that cultured mesangial cells exposed to high ambient glucose arrest in the G1 phase of the cell cycle and that this is associated with an increased expression of inhibitors of the cyclin-dependent kinase (CDK)-inhibitors p21(Cip) and p27(Kip1). To further investigate a potential role of p27Kip1 in the development of glucose-induced hypertrophy, mesangial cells from p27Kip1 wild-type (+/+) and knockout (-/-) mice were established. High glucose medium (450 mg/dl) increased p21(Cip1) protein in p27Kip1+/+ and -/- mesangial cells, and increased p27Kip1 protein levels in p27Kip1+/+ cells. In contrast to high glucose increasing de novo protein synthesis in p27Kip1+/+ cells, high glucose did not increase protein synthesis in p27Kip1-/- cells. High glucose also reduced DNA synthesis and caused cell cycle arrest in p27Kip1+/+ cells. In contrast, despite an increase in transforming growth factor (TGF)-beta mRNA and protein expression, DNA synthesis and cell cycle progression were increased by high glucose in p27Kip1-/- cells. Exogenous TGF-beta comparably induced fibronectin mRNA in p27Kip1+/+ and -/- cells suggesting intact TGF-beta receptor transduction. In addition, high glucose failed to increase the total protein/cell number ratio in p27Kip1-/- cells. However, in the presence of high glucose, reconstituting p27Kip1 expression by transient or stable transfection in p27Kip1-/- cells, using an inducible expression system, increased the de novo protein synthesis and restored G1-phase arrest. These results show that p27Kip1 is required for glucose-induced mesangial cell hypertrophy and cell cycle arrest.

Animals↗
PubMed2001

Kainate-induced seizures alter protein composition and N-methyl-D-aspartate receptor function of rat forebrain postsynaptic densities.

The postsynaptic density is a highly dynamic structure, which is reorganized in an activity-dependent manner. An animal model for temporal lobe epilepsy, i.e. kainate-induced limbic seizures in rats, was used to study changes in postsynaptic density composition after extensive synaptic activity. Six hours after kainate injection, the protein content of the postsynaptic density fractions from rats that developed strong seizures was increased three-fold compared to saline-treated controls. Immunoblot analysis revealed that the relative amounts of metabotropic glutamate receptor 1alpha, N-ethylmaleimide-sensitive fusion protein, protein kinases C, Fyn and TrkB, as well as the neuronal nitric oxide synthase, were significantly higher in seizure-developing than in control rats. In contrast, the relative contents of the kainate receptor KA2 subunit, beta-actin, alpha-adducin and the membrane-associated guanylate kinase homolog SAP90/PSD-95 were decreased. The relative amounts of additional postsynaptic density proteins, including alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and N-methyl-D-aspartate receptor subunits, calcium/calmodulin-dependent kinase type II, casein kinase 2, tubulin, microtubule-associated protein 2B, the membrane-associated guanylate kinase homolog SAP102, and proline-rich synapse-associated protein 1/cortactin binding protein 1/Shank2 remained essentially unchanged. To assess possible changes in postsynaptic performance, postsynaptic densities were isolated from control and epileptic rats, incorporated into giant liposomes and N-methyl-D-aspartate receptor currents were recorded. A significant reduction in the mean conductance was observed in patches containing postsynaptic densities from animals with high seizure activity. This was due to the presence of reduced conductance levels in each membrane patch compared to control postsynaptic density preparations. From these data, we suggest that intense synaptic activity associated with seizures modifies the composition of postsynaptic densities and has profound consequences on the function of the N-methyl-D-aspartate receptors present in them. This rearrangement may accompany impairment of synaptic plasticity.

Animals↗
PubMed2001

Leptin stimulates type I collagen production in db/db mesangial cells: glucose uptake and TGF-beta type II receptor expression.

BACKGROUND: Serum leptin levels correlate with fat cell mass and are elevated in patients with massive obesity and type 2 diabetes mellitus, which are strong risk factors for the development of glomerulosclerosis. We have previously shown in cultured glomerular endothelial cells that leptin stimulates cellular proliferation and expression of the prosclerotic cytokine transforming growth factor-beta1 (TGF-beta1). Although the effect of leptin on the hypothalamus to regulate energy homeostasis is well known, the effect of leptin on the kidney, and specifically on the glomerular mesangial cell, is unclear. METHODS: The obese, diabetic db/db mouse, which lacks the functional full-length Ob-Rb leptin receptor, is a suitable model to assess the effects of hyperleptinemia on peripheral tissues that express other receptor isoforms. The effects of leptin on glucose uptake, the TGF-beta system, and type I collagen production were evaluated in db/db mouse mesangial cells in culture. A phosphatidylinositol-3 kinase (PI-3K) inhibitor was used to assess the role of PI-3K in mediating the effects of leptin. RESULTS: A short form of the leptin receptor (Ob-Ra), but not Ob-Rb, was present by reverse transcription-polymerase chain reaction in the kidney and mesangial cells of both nondiabetic db/m and diabetic db/db mice. In db/db mesangial cells, leptin increased 2-deoxy-D-glucose (2DOG) uptake dose dependently and stimulated gene expression of TGF-beta type II receptor (TbetaRII) and alpha1(I) collagen, but not TGF-beta1. Protein production of type I collagen (enzyme-linked immunosorbent assay) was also increased by leptin. Both leptin-stimulated 2DOG uptake and type I collagen production were suppressed by a PI-3K inhibitor, LY294002. Mesangial cells pretreated with leptin exhibited increased responsiveness to exogenous TGF-beta1, as evidenced by a greater production of type I collagen protein in leptin-pretreated cells exposed to low-dose TGF-beta1 (0.5 ng/mL). The addition of both TGF-beta1 (2 ng/mL) and leptin (100 ng/mL) increased type I collagen production more than addition of either TGF-beta1 or leptin alone. CONCLUSIONS: Leptin increases glucose uptake and type I collagen in db/db mesangial cells through a PI-3K-dependent pathway. We postulate that increased leptin levels may transmit a signal through the short-form leptin receptor to up-regulate TbetaRII and activate the intraglomerular TGF-beta system, which may contribute to the glomerulosclerosis of obesity or type 2 diabetes.

Animals↗
PubMed2001

Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimental glomerulonephritis.

BACKGROUND: This study evaluated the mechanisms of monocyte/macrophage (M/M) infiltration in a rat model of anti-glomerular basement membrane glomerulonephritis (GN). We focused on chemokines and osteopontin, which are known regulators of M/M recruitment. METHODS: Using immunohistology, in situ hybridization, and Northern blotting, the expression levels of chemokines and osteopontin were evaluated in isolated glomeruli and tubules 4, 10, and 20 days after the induction of GN. In vivo blocking experiments were performed by application of neutralizing antibodies against osteopontin and monocyte chemoattractant protein-1 (MCP-1). RESULTS: In nephritic animals, high glomerular MCP-1 and RANTES (regulated upon activation normal T cell expressed and secreted) expression levels were observed on days 4 and 10. The tubular expression of MCP-1, however, was only slightly enhanced. In contrast, tubular osteopontin production was maximally stimulated (day 10) and paralleled with peaks of albuminuria and tubulointerstitial M/M infiltration. Application of an anti-osteopontin antibody ameliorated tubulointerstitial and glomerular M/M recruitment, whereas treatment with an anti-MCP-1 antibody selectively reduced glomerular M/M recruitment. However, tubulointerstitial M/M infiltration remained unchanged. CONCLUSION: These studies show that chemokines and osteopontin are differentially expressed in glomeruli and tubules in this model of GN. Chemokines play a primary role in the glomeruli, whereas osteopontin has a predominant role in tubulointerstitial M/M recruitment. The roles of chemokines and osteopontin may thus be dependent on the renal compartment and on the disease model.

Albuminuria↗
PubMed2001

Renal handling of human apolipoprotein(a) and its fragments in the rat.

The sites and mechanisms of the catabolism of atherogenic lipoprotein(a) (Lp(a)) are not well understood. Lp(a) is increased in patients with end-stage renal disease, suggesting a renal catabolism of Lp(a). To gain a better insight into renal handling of Lp(a), we established a heterologous rat model to study the renal catabolism of human Lp(a). Pure human Lp(a) was injected into Wistar rats, and animals were sacrificed at different time points (30 minutes to 24 hours). Intact Lp(a) was cleared from the circulation of injected rats with a half-life time of 14.5 hours. Strong intracellular immunostaining for apolipoprotein(a) (apo(a)) was observed in the cytoplasm of proximal tubular cells after 4, 8, and 24 hours. Apolipoprotein B (apoB) was colocalized with glomerular apo(a) 1 to 8 hours after Lp(a) injection, but renal capillaries and tubules remained negative. No relevant amounts of apo(a) fragments were found in the plasma of rats after injection of Lp(a). During all urine collection periods, apo(a) fragments with molecular weights of 50 to 160 kd were detected in the urine, however. Our results show that human Lp(a) injected into rats accumulates intracellularly in the rat kidney, and apo(a) fragments are excreted in the urine. The kidney apparently plays a major role in fragmentation of Lp(a). Despite the fact that rodents lack endogenous Lp(a), rats injected with human Lp(a) may provide a useful heterologous animal model to study the renal metabolism of Lp(a) further.

Animals↗