A M Schmidt

Columbia University, New York, New York, United States

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Publications (64)446.35 Total impact

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    ABSTRACT: Objective: A link between periodontal infections and an increased risk for vascular disease has been demonstrated. Porphyromonas gingivalis localizes in human atherosclerotic plaques, accelerates atherosclerosis in animal models and modulates vascular cell function. The receptor for advanced glycation endproducts (RAGE) regulates vascular inflammation and atherogenesis. We hypothesized that RAGE is involved in P. gingivalis's contribution to proatherogenic responses in vascular endothelial cells (EC). Methods: Murine aortic endothelial cells (MAEC) isolated from wild type C57BL/6 or homozygous RAGE-/- mice were infected with P. gingivalis, strain 381, or left uninfected. Cell lysates and supernatants were collected 6h and 24h later. Lysates were used for detection of RAGE by immunobloting. Levels of advanced glycation endproducts (AGEs) and monocyte chemoattractant protein 1 (MCP-1) were measured in supernatants by ELISA. In blocking experiments, MCP-1 production was assessed in primary human aortic endothelial cells (HAEC) incubated with anti-RAGE IgG, or anti-AGE IgG, or the AGE inhibitor aminoguanidine for 2h prior and 6h following infection. Experiments were repeated at least three times. Results: P. gingivalis infection enhanced expression of RAGE in wild-type MAEC (2.4-fold at 6h, p=0.0122; 1.3-fold at 24h, p=0.0128) and increased production of proatherogenic MCP-1 (2.0-fold at 6h, p<0.0001; 1.7-fold at 24h, p<0.0001). Consistent with a role for RAGE-dependent EC activation, MCP-1 levels were unaffected in infected RAGE-/- MAEC, and in infected HAEC following RAGE blockade. Infection of wild-type MAEC significantly increased AGE ligands, which have been shown to drive the receptor's activation and subsequent events (2.4-fold at 6h, p=0.0003; 3.3-fold at 24h, p=0.0041). P. gingivalis infection did not increase AGE production in RAGE-/- MAEC. Both AGE blocking agents, significantly suppressed MCP-1 levels in infected HAEC. Conclusion: The present findings implicate for the first time the AGE-RAGE axis in the amplification of proatherogenic responses triggered by P. gingivalis in vascular endothelial cells. Supported by DE14575
    IADR General Session 2010; 07/2010
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    ABSTRACT: Porphyromonas gingivalis, a major periodontal pathogen, has been reported to be involved in atherogenesis. In order to further understand this pathogen's link with systemic inflammation and vascular disease, we investigated its influence on murine monocytes and macrophages from three different sources. Concanavalin A-elicited peritoneal macrophages, peripheral blood monocyte-derived macrophages and WEHI 274.1 monocytes were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. Infection with P. gingivalis 381 markedly induced monocyte migration and significantly enhanced production of the pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6. Consistent with a role for this pathogen's major fimbriae and/or its invasive capacity, infection with DPG3 had a minimal effect on both monocyte attraction and pro-inflammatory cytokine production. Since monocyte recruitment and activation are important steps in the development of vascular inflammation and atherosclerosis, these results suggest that P. gingivalis infection may be involved in these processes.
    Journal of Periodontal Research 09/2009; 45(2):239-45. DOI:10.1111/j.1600-0765.2009.01225.x · 2.22 Impact Factor
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    ABSTRACT: The receptor for advanced glycation endproducts (RAGE), a multiligand member of the immunoglobulin superfamily, interacts with proinflammatory AGEs, the products of nonenzymatic glycation and oxidation of proteins; high-mobility group box 1 (HMGB1), also known as amphoterin and S100/calgranulins to amplify inflammation and tissue injury. Previous studies showed that blockade of RAGE suppressed recruitment of proinflammatory mechanisms in murine models. We tested the hypothesis that RAGE contributes to alloimmune responses and report that in vivo, acute rejection of fully allogeneic cardiac allografts in a murine model of heterotopic cardiac transplantation is significantly delayed by pharmacological antagonism of RAGE. In parallel, allogeneic T-cell proliferation in the mixed lymphocyte reaction is, at least in part, RAGE-dependent. These data provide the first insights into key roles for RAGE in allorecognition responses and suggest that antagonism of this receptor may exert beneficial effects in allogeneic organ transplantation.
    American Journal of Transplantation 03/2007; 7(2):293-302. DOI:10.1111/j.1600-6143.2006.01617.x · 6.19 Impact Factor
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    ABSTRACT: Multiple studies have demonstrated a link between periodontal infections and vascular disease. Porphyromonas gingivalis, a major periodontal pathogen, has been shown to adhere to and invade endothelial cells. In order to dissect mechanisms underlying these observations, we assessed the role of P. gingivalis infection in modulating properties of endothelial cells linked to atherothrombosis. Primary human aortic endothelial cells (HAEC) were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. Markers of coagulation and thrombosis were assessed 8 h and 18 h postinfection in cell lysates and supernatants. Infection with P. gingivalis 381 significantly enhanced tissue factor expression and activity, and suppressed levels of tissue factor pathway inhibitor. Furthermore, P. gingivalis infection decreased levels and activity of tissue plasminogen activator, and enhanced plasminogen activator inhibitor-1 antigen and activity. Consistent with an important role for bacterial adhesion/invasion in this setting, infection with DPG3 failed to induce procoagulant properties in HAEC. Most of the above effects of P. gingivalis 381 were more apparent at the later time point (18 h postinfection). This suggests that P. gingivalis infection, rather than having an immediate and direct effect, might activate pathways that, in turn, trigger endothelial procoagulant mechanisms. Taken together these data demonstrate for the first time that infection with a periodontal pathogen induces procoagulant responses in HAEC.
    Journal of Thrombosis and Haemostasis 11/2006; 4(10):2256-61. DOI:10.1111/j.1538-7836.2006.02128.x · 5.55 Impact Factor
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    S Cellek, W Qu, A M Schmidt, S Moncada
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    ABSTRACT: We have previously shown that in diabetes nitrergic neurones innervating the urogenital and gastrointestinal organs undergo a selective degenerative process. This comprises an initial insulin-reversible decrease in neuronal nitric oxide synthase (nNOS) in the axons, followed by apoptosis of the nitrergic neurones, a process that is not reversible by insulin. Since apoptosis was independent of serum glucose concentrations, and advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of diabetic complications, we have now measured AGEs in the serum and penis, pyloric sphincter and pelvic ganglia of diabetic animals at different times after streptozotocin treatment. Furthermore, we have studied their effect in vitro on human neuroblastoma (SH-SY5Y) cells in the presence or absence of nNOS expression. Serum AGEs were measured using fluorometry and ELISA. Accumulation of AGEs in the tissues was evaluated with immunohistochemistry. The viability, apoptosis and oxidative stress in SH-SY5Y cells were measured upon exposure to AGEs or high concentrations of glucose. AGEs increased gradually in the serum and tissues of streptozotocin-induced diabetic rats; this process was not affected by delayed insulin treatment. In SH-SY5Y cells, AGEs, but not high glucose concentrations, increased the reactive oxygen species and caspase-3-dependent apoptosis in a synergistic fashion with endogenous nitric oxide (NO). Apoptosis was prevented by treatment with a NOS inhibitor, a pan-caspase inhibitor, a soluble receptor of AGEs or an anti-oxidant, but not an inhibitor of soluble guanylate cyclase. The synergistic actions of NO and AGEs account for the irreversible nitrergic degeneration in diabetes.
    Diabetologia 03/2004; 47(2):331-9. DOI:10.1007/s00125-003-1298-y · 6.88 Impact Factor
  • The Journal of Heart and Lung Transplantation 01/2003; 22(1):S100. DOI:10.1016/S1053-2498(02)00758-1 · 5.61 Impact Factor
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    ABSTRACT: Receptor for AGE (RAGE) is a member of the immunoglobulin superfamily that engages distinct classes of ligands. The biology of RAGE is driven by the settings in which these ligands accumulate, such as diabetes, inflammation, neurodegenerative disorders and tumors. In this review, we discuss the context of each of these classes of ligands, including advance glycation end-products, amyloid beta peptide and the family of beta sheet fibrils, S100/calgranulins and amphoterin. Implications for the role of these ligands interacting with RAGE in homeostasis and disease will be considered.
    Cellular and Molecular Life Sciences CMLS 08/2002; 59(7):1117-28. DOI:10.1007/s00018-002-8491-x · 5.86 Impact Factor
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    ABSTRACT: The receptor for advanced glycation end products (RAGE) and its proinflammatory S100/calgranulin ligands are enriched in joints of subjects with rheumatoid arthritis (RA) and amplify the immune/inflammatory response. In a model of inflammatory arthritis, blockade of RAGE in mice immunized and challenged with bovine type II collagen suppressed clinical and histologic evidence of arthritis, in parallel with diminished levels of TNF-alpha, IL-6, and matrix metalloproteinases (MMP) 3, 9 and 13 in affected tissues. Allelic variation within key domains of RAGE may influence these proinflammatory mechanisms, thereby predisposing individuals to heightened inflammatory responses. A polymorphism of the RAGE gene within the ligand-binding domain of the receptor has been identified, consisting of a glycine to serine change at position 82. Cells bearing the RAGE 82S allele displayed enhanced binding and cytokine/MMP generation following ligation by a prototypic S100/calgranulin compared with cells expressing the RAGE 82G allele. In human subjects, a case-control study demonstrated an increased prevalence of the 82S allele in patients with RA compared with control subjects. These data suggest that RAGE 82S upregulates the inflammatory response upon engagement of S100/calgranulins, and, thereby, may contribute to enhanced proinflammatory mechanisms in immune/inflammatory diseases.
    Genes and Immunity 06/2002; 3(3):123-35. DOI:10.1038/sj.gene.6363861 · 3.79 Impact Factor
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    ABSTRACT: Current investigational models of murine colitis and colon cancer necessitate sacrifice of animals in order to obtain colonic tissue. The purpose of this study was to develop a safe method of murine colonoscopy that would allow serial evaluation and mucosal biopsies of the same animal. Nine mice (two C3H, two C57/BL6, and five IL-10 deficient) were studied a total of four times each over 4 weeks. Three mice [APC (Min +/-)] were examined three times each. Mice were gavaged with 1 cc of a polyethylene glycol solution on the day prior to colonoscopy. Solid chow was withheld and the mice were maintained on Pedialyte. Mice were anesthetized with ketamine and xylazine. A flexible pediatric cystoscope (2.1-mm diameter) with a single biopsy channel was introduced per anum, and the colon was gently insufflated with air to a mean pressure of less than 5 mmHg. Saline irrigation was used when necessary. A single biopsy was obtained from the rectosigmoid colon during each examination. A total of 46 examinations were carried out. One mouse died after being anesthesized for the fourth examination, and two mice [one IL-10 knockout and one APC (Min+/-)] died one day after the 3rd examination. No other complications were noted. The average length of insertion was 3 cm. Transillumination allowed for localization of the endoscope tip. Biopsies, although quite small, were sufficient for pathologic evaluation and diagnosis. Murine colonoscopy is a safe and feasible technique. It permits consecutive visual and histopathological examinations, and it allows the investigator to monitor the response of the murine colon to experimental interventions.
    Surgical Endoscopy 02/2002; 16(1):22-4. DOI:10.1007/s004640080168 · 3.31 Impact Factor
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    ABSTRACT: Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-kappaB in vitro, we observed a long-lasting sustained activation of NF-kappaB in the absence of decreased IkappaBalpha in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-kappaBp65. A comparable increase in NF-kappaBp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-beta peptide (Abeta) to the transmembrane receptor for AGE (RAGE) results in protein synthesis-dependent sustained activation of NF-kappaB both in vitro and in vivo. Infusion of AGE-albumin into mice bearing a beta-globin reporter transgene under control of NF-kappaB also resulted in prolonged expression of the reporter transgene. In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-kappaB (p50/p65) from the cytoplasm into the nucleus for >1 week. Sustained NF-kappaB activation by ligands of RAGE was mediated by initial degradation of IkappaB proteins followed by new synthesis of NF-kappaBp65 mRNA and protein in the presence of newly synthesized IkappaBalpha and IkappaBbeta. These data demonstrate that ligands of RAGE can induce sustained activation of NF-kappaB as a result of increased levels of de novo synthesized NF-kappaBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF-kappaB activation observed in hyperglycemia and possibly other chronic diseases.
    Diabetes 12/2001; 50(12):2792-808. DOI:10.2337/diabetes.50.12.2792 · 8.47 Impact Factor
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    A M Schmidt, D M Stern
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    ABSTRACT: Receptor for AGE (RAGE), a member of the immunoglobulin superfamily, was first identified as a specific cell surface interaction site for Advanced Glycation Endproducts, or AGEs. AGEs, the products of nonenzymatic glycation/oxidation of proteins/lipids, accumulate in natural aging and disorders such as diabetes, renal failure and amyloidoses. Interaction of AGEs with RAGE has been linked to chronic inflammatory and vascular dysfunction that characterizes the chronic complications of these disorders. Recent studies have indicated that RAGE is a multiligand receptor, serving as a specific cell surface, signal transducing receptor for amphoterin, a molecule with implications for neurite outgrowth in neuronal development and in tumor cell proliferation and spread. RAGE is also a receptor for amyloid-beta peptide, whose interaction with neuronal and microglial RAGE within the CNS is linked to sustained inflammation and neuronal toxicity and cell death. RAGE also serves as a signal-transducing receptor for EN-RAGEs, and related members of the S100/calgranulin family of proinflammatory cytokines; consequences of this interaction include initiation and propagation of inflammatory responses. Consistent with an important role for ligand-RAGE interaction in these settings, blockade of RAGE suppresses chronic cellular activation and dysfunction in murine models of diabetic complications, inflammation and tumor proliferation and metastasis. Taken together, an new paradigm is emerging which links RAGE, a gene encoded within the Major Histocompatibility Complex (MHC) Class III regions, to central host response mechanisms in homeostasis and chronic disease.
    Frontiers in Bioscience 11/2001; 6:D1151-60. DOI:10.2741/Schmidt · 4.25 Impact Factor
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    ABSTRACT: Advanced glycation end products (AGEs) and their cell surface receptor, RAGE, have been implicated in the pathogenesis of diabetic complications. Here, we studied the role of RAGE and expression of its proinflammatory ligands, EN-RAGEs (S100/calgranulins), in inflammatory events mediating cellular activation in diabetic tissue. Apolipoprotein E-null mice were rendered diabetic with streptozotocin at 6 weeks of age. Compared with nondiabetic aortas and kidneys, diabetic aortas and kidneys displayed increased expression of RAGE, EN-RAGEs, and 2 key markers of vascular inflammation, vascular cell adhesion molecule (VCAM)-1 and tissue factor. Administration of soluble RAGE, the extracellular domain of the receptor, or vehicle to diabetic mice for 6 weeks suppressed levels of VCAM-1 and tissue factor in the aorta, in parallel with decreased expression of RAGE and EN-RAGEs. Diabetic kidney demonstrated increased numbers of EN-RAGE-expressing inflammatory cells infiltrating the glomerulus and enhanced mRNA for transforming growth factor-beta, fibronectin, and alpha(1) (IV) collagen. In mice treated with soluble RAGE, the numbers of infiltrating inflammatory cells and mRNA levels for these glomerular cytokines and components of extracellular matrix were decreased. These data suggest that activation of RAGE primes cells targeted for perturbation in diabetic tissues by the induction of proinflammatory mediators.
    Arteriosclerosis Thrombosis and Vascular Biology 07/2001; 21(6):905-10. DOI:10.1161/01.ATV.21.6.905 · 6.34 Impact Factor
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    ABSTRACT: Engagement of the receptor for advanced glycation end products (RAGE) by products of nonenzymatic glycation/oxidation triggers the generation of reactive oxygen species (ROS), thereby altering gene expression. Because dissection of the precise events by which ROS are generated via RAGE is relevant to the pathogenesis of complications in AGE-related disorders, such as diabetes and renal failure, we tested the hypothesis that activation of NADPH oxidase contributed, at least in part, to enhancing oxidant stress via RAGE. Here we show that incubation of human endothelial cells with AGEs on the surface of diabetic red blood cells, or specific AGEs, (carboxymethyl)lysine (CML)-modified adducts, prompted intracellular generation of hydrogen peroxide, cell surface expression of vascular cell adhesion molecule-1, and generation of tissue factor in a manner suppressed by treatment with diphenyliodonium, but not by inhibitors of nitric oxide. Consistent with an important role for NADPH oxidase, although macrophages derived from wild-type mice expressed enhanced levels of tissue factor upon stimulation with AGE, macrophages derived from mice deficient in a central subunit of NADPH oxidase, gp91phox, failed to display enhanced tissue factor in the presence of AGE. These findings underscore a central role of NADPH oxidase in AGE-RAGE-mediated generation of ROS and provide a mechanism for altered gene expression in AGE-related disorders.
    AJP Endocrinology and Metabolism 06/2001; 280(5):E685-94. · 4.09 Impact Factor
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    A M Schmidt, D M Stern
    Arteriosclerosis Thrombosis and Vascular Biology 04/2001; 21(3):297-9. DOI:10.1161/01.ATV.21.3.297 · 6.34 Impact Factor
  • S D Yan, A M Schmidt, D Stern
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    ABSTRACT: Neurotoxicity of beta-amyloid peptide (A beta) in Alzheimer's disease (AD) is usually thought to arise from the nonspecific effects of high concentrations of A beta on vulnerable neurons, resulting in membrane destabilization and increasing intracellular calcium concentration. This review advances the hypothesis that at early stages of AD, when A beta is present in lower amounts, its ability to perturb the function of cellular targets is mediated by specific cofactors present on the cell surface and intracellularly. Receptor for advanced glycation endproducts (RAGE) is a cell-surface receptor which binds A beta and amplifies its effects on cells in the nanomolar range. The intracellular enzyme A beta-binding alcohol dehydrogenase (ABAD) is likely to engage nascent A beta formed in the endoplasmic reticulum, and to mediate cell stress from this site. The analysis of A beta interaction with RAGE and ABAD, as well as other cofactors, provides insight into new mechanisms and, potentially, identifies therapeutic targets relevant to neuronal dysfunction in AD.
    Biochemical Society Symposium 02/2001; · 2.74 Impact Factor
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    ABSTRACT: In patients with amyloid beta-related cerebrovascular disorders, e.g. , Alzheimer's disease, one finds increased deposition of amyloid peptide (Abeta) and increased presence of monocyte/microglia cells in the brain. However, relatively little is known of the role of Abeta in the trafficking of monocytes across the blood-brain barrier (BBB). Our studies show that interaction of Abeta(1-40) with monolayer of human brain endothelial cells results in augmented adhesion and transendothelial migration of monocytic cells (THP-1 and HL-60) and peripheral blood monocytes. The Abeta-mediated migration of monocytes was inhibited by antibody to Abeta receptor (RAGE) and platelet endothelial cell adhesion molecule (PECAM-1). Additionally, Abeta-induced transendothelial migration of monocytes were inhibited by protein kinase C inhibitor and augmented by phosphatase inhibitor. We conclude that interaction of Abeta with RAGE expressed on brain endothelial cells initiates cellular signaling leading to the transendothelial migration of monocytes. We suggest that increased diapedesis of monocytes across the BBB in response to Abeta present either in the peripheral circulation or in the brain parenchyma may play a role in the pathophysiology of Abeta-related vascular disorder.
    AJP Cell Physiology 01/2001; 279(6):C1772-81. · 3.67 Impact Factor
  • A M Schmidt, D M Stern
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    ABSTRACT: Although the underlying causes of hyperglycemia are multiple, a common thread associated with high levels of blood sugar is the development of a range of vascular and inflammatory complications that might seriously limit the quality and duration of life in affected individuals. Despite multiple aggressive efforts to prevent complications, diabetes remains the leading disease consuming healthcare dollars in the USA. This review focuses on the role of advanced glycation endproducts (AGEs) and their interaction with their signal-transduction AGE receptor (RAGE), in vascular and inflammatory cell perturbation and the chronic activation that underlies diabetes. Our studies provide mechanistic insights into complications within the macrovasculature and those ensuing from an exaggerated host response to invading bacteria, and suggest that blockade of RAGE might provide a potent and safe strategy for the prevention of complications that typify long-term diabetes.
    Trends in Endocrinology and Metabolism 12/2000; 11(9):368-75. DOI:10.1016/S1043-2760(00)00311-8 · 8.87 Impact Factor
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    A M Schmidt, D M Stern
    Circulation Research 11/2000; 87(9):722-4. DOI:10.1161/01.RES.87.9.722 · 11.09 Impact Factor
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    ABSTRACT: Advanced glycation end products (AGE) contribute to diabetic tissue injury by two major mechanisms, i.e., the alteration of extracellular matrix architecture through nonenzymatic glycation, with formation of protein crosslinks, and the modulation of cellular functions through interactions with specific cell surface receptors, the best characterized of which is the receptor for AGE (RAGE). Recent evidence suggests that the AGE-RAGE interaction may also be promoted by inflammatory processes and oxidative cellular injury. To characterize the distributions of AGE and RAGE in diabetic kidneys and to determine their specificity for diabetic nephropathy, an immunohistochemical analysis of renal biopsies from patients with diabetic nephropathy (n = 26), hypertensive nephrosclerosis (n = 7), idiopathic focal segmental glomerulosclerosis (n = 11), focal sclerosis secondary to obesity (n = 7), and lupus nephritis (n = 11) and from normal control subjects (n = 2) was performed, using affinity-purified antibodies raised to RAGE and two subclasses of AGE, i.e., N(epsilon)-(carboxymethyl)-lysine (CML) and pentosidine (PENT). AGE were detected equally in diffuse and nodular diabetic nephropathy. CML was the major AGE detected in diabetic mesangium (96%), glomerular basement membranes (GBM) (42%), tubular basement membranes (85%), and vessel walls (96%). In diabetic nephropathy, PENT was preferentially located in interstitial collagen (90%) and was less consistently observed in vessel walls (54%), mesangium (77%), GBM (4%), and tubular basement membranes (31%). RAGE was expressed on normal podocytes and was upregulated in diabetic nephropathy. The restriction of RAGE mRNA expression to glomeruli was confirmed by reverse transcription-PCR analysis of microdissected renal tissue compartments. The extent of mesangial and GBM immunoreactivity for CML, but not PENT, was correlated with the severity of diabetic glomerulosclerosis, as assessed pathologically. CML and PENT were also identified in areas of glomerulosclerosis and arteriosclerosis in idiopathic and secondary focal segmental glomerulosclerosis, hypertensive nephrosclerosis, and lupus nephritis. In active lupus nephritis, CML and PENT were detected in the proliferative glomerular tufts and crescents. In conclusion, CML is a major AGE in renal basement membranes in diabetic nephropathy, and its accumulation involves upregulation of RAGE on podocytes. AGE are also accumulated in acute inflammatory glomerulonephritis secondary to systemic lupus erythematosus, possibly via enzymatic oxidation of glomerular matrix proteins.
    Journal of the American Society of Nephrology 10/2000; 11(9):1656-66. · 9.47 Impact Factor
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    ABSTRACT: Insights into factors underlying causes of familial Alzheimer's disease (AD), such as mutant forms of beta-amyloid precursor protein and presenilins, and those conferring increased risk of sporadic AD, such as isoforms of apolipoprotein E and polymorphisms of alpha2-macroglobulin, have been rapidly emerging. However, mechanisms through which amyloid beta-peptide (Abeta), the fibrillogenic peptide most closely associated with neurotoxicity in AD, exerts its effects on cellular targets have only been more generally outlined. Late in the course of AD, when Abeta fibrils are abundant, non-specific interactions of amyloid with cellular elements are likely to induce broad cytotoxicity. However, early in AD, when concentrations of Abeta are much lower and extracellular deposits are infrequent, mechanisms underlying cellular dysfunction have not been clearly defined. The key issue in elucidating the means through which Abeta perturbs cellular properties early in AD is the possibility that protective therapy at such times may prevent cytotoxicity at a point when damage is still reversible. This brief review focusses on two cellular cofactors for Abeta-induced cellular perturbation: the cell surface immunoglobulin superfamily molecule RAGE (receptor for advanced glycation endproducts) and ABAD (Abeta binding alcohol dehydrogenase). Although final proof for the involvement of these cofactors in cellular dysfunction in AD must await the results of further in vivo experiments, their increased expression in AD brain, as well as other evidence described below, suggests the possibility of specific pathways for Abeta-induced cellular perturbation which could provide future therapeutic targets.
    Biochimica et Biophysica Acta 08/2000; 1502(1):145-57. · 4.66 Impact Factor

Publication Stats

12k Citations
446.35 Total Impact Points


  • 1993–2010
    • Columbia University
      • • College of Physicians and Surgeons
      • • Department of Surgery
      • • Department of Physiology and Cellular Biophysics
      • • Department of Medicine
      New York, New York, United States
  • 2001
    • Institut National de la Transfusion Sanguine, Paris
      Lutetia Parisorum, Île-de-France, France
    • University of Greifswald
      • Department of Laboratory Animal Science
      Griefswald, Mecklenburg-Vorpommern, Germany
  • 2000
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany
  • 1992–2000
    • CUNY Graduate Center
      New York City, New York, United States
  • 1999
    • New York Medical College
      • Department of Medicine
      New York City, NY, United States
  • 1998
    • University of Pennsylvania
      • Department of Pathology
      Philadelphia, PA, United States
  • 1996
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France
  • 1995
    • Universität Heidelberg
      • Medical Psychology
      Heidelburg, Baden-Württemberg, Germany