Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin, when administered to patients undergoing operations using cardiopulmonary bypass, induces plasma changes that gradually impair platelet macroaggregation, but heparinization of whole blood in vitro does not have this effect. The plasma changes induced by heparin in vivo continue to progress in whole blood ex vivo. Heparin releases several endothelial proteins, including lipoprotein lipase, hepatic lipase, platelet factor-4 and superoxide dismutase. These enzymes, which remain active in plasma ex vivo, may impair platelet macroaggregation after in vivo heparinization and during cardiopulmonary bypass. In the present study, proteins were added in vitro to hirudin (200 units.ml(-1))-anticoagulated blood from healthy volunteers, and the platelet macroaggregatory responses to ex vivo stimulation with collagen (0.6 microg.ml(-1)) were assessed by whole-blood impedance aggregometry. Over a 4 h period, human lipoprotein lipase and human hepatic lipase reduced the platelet macroaggregatory response from 17.0+/-2.3 to 1.5+/-1.3 and 1.2+/-0.6 Omega respectively (means+/-S.D.) (both P <0.01; n =6). Other lipoprotein lipases also impaired platelet macroaggregation, but platelet factor-4 and superoxide dismutase did not. Platelet macroaggregation showed an inverse linear correlation with plasma concentrations of non-esterified fatty acids ( r (2)=0.69; two-sided P <0.0001; n =8), suggesting that heparin-induced lipolysis inhibits platelet macroaggregation. Lipoprotein degradation products may cause this inhibition by interfering with eicosanoids and other lipid mediators of metabolism.
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PMID:Lipolysis generates platelet dysfunction after in vivo heparin administration. 1224 44

Explant cultures of adult human trabecular bone fragments give rise to osteoblastic cells, that are known to express osteoblast-related genes and mineralize extracellular matrix. These osteoblastic cells have also been shown to undergo adipogenesis in vitro and chondrogenesis in vivo. Here we report the in vitro developmental potential of adult human osteoblastic cells (hOB) derived from explant cultures of collagenase-pretreated trabecular bone fragments. In addition to osteogenic and adipogenic differentiation, these cells are capable of chondrogenic differentiation in vitro in a manner similar to adult human bone marrow-derived mesenchymal progenitor cells. High-density pellet cultures of hOB maintained in chemically defined serum-free medium, supplemented with transforming growth factor-beta1, were composed of morphologically distinct, chondrocyte-like cells expressing mRNA transcripts of collagen types II, IX and X, and aggrecan. The cells within the high-density pellet cultures were surrounded by a sulfated proteoglycan-rich extracellular matrix that immunostained for collagen type II and proteoglycan link protein. Osteogenic differentiation of hOB was verified by an increased number of alkaline phosphatase-positive cells, that expressed osteoblast-related transcripts such as alkaline phosphatase, collagen type I, osteopontin and osteocalcin, and formed mineralized matrix in monolayer cultures treated with ascorbate, beta-glycerophosphate, and bone morphogenetic protein-2. Adipogenic differentiation of hOB was determined by the appearance of intracellular lipid droplets, and expression of adipocyte-specific genes, such as lipoprotein lipase and peroxisome proliferator-activated receptor gamma2, in monolayer cultures treated with dexamethasone, indomethacin, insulin and 3-isobutyl-1-methylxanthine. Taken together, these results show that cells derived from collagenase-treated adult human trabecular bone fragments have the potential to differentiate into multiple mesenchymal lineages in vitro, indicating their developmental plasticity and suggesting their mesenchymal progenitor nature.
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PMID:Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells. 1238 74

Dexamethasone is capable of directing osteoblastic differentiation of bone marrow stromal cells (BMSCs) in vitro, but its effects are not lineage-specific, and sustained exposure has been shown to down-regulate collagen synthesis and induce maturation of an adipocyte subpopulation within BMSC cultures. Such side effects might be reduced if dexamethasone is applied in a regimented manner, but the discrete steps in osteoblastic maturation that are stimulated by dexamethasone are not known. To examine this, dexamethasone was added to medium to initiate differentiation of rat BMSCs cultures and then removed after a varying number of days. Cell layers were analyzed for cell number, rate of collagen synthesis, expression of osteocalcin (OC), bone sialoprotein (BSP) and lipoprotein lipase (LpL), and matrix mineralization. Withdrawal of dexamethasone at 3 and 10 days was found to enhance cell number relative to continuous exposure, but did not affect to decrease collagen synthesis slightly. Late markers of osteoblastic differentiation, BSP expression and matrix mineralization, were also sensitive to dexamethasone and increased systematically with exposure while LpL systematically decreased. These results indicate that dexamethasone acts at both early and late stages to direct proliferative osteoprogenitor cells toward terminal maturation.
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PMID:Effect of dexamethasone withdrawal on osteoblastic differentiation of bone marrow stromal cells. 1293 52

Recently, cell-based approaches utilizing adipogenic progenitor cells for fat tissue engineering have been developed and reported to have success in promoting in vivo adipogenesis and the repair of defect sites. For autologous applications, human bone marrow-derived mesenchymal stem cells (MSCs) have been suggested as a potential cell source for adipose tissue engineering applications due to their ability to be isolated and ex vivo expanded from adult bone marrow aspirates and their versatility for pluripotent differentiation into various mesenchymal lineages including adipogenic. Due to the relatively low frequency of MSCs present within bone marrow, extensive ex vivo expansion of these cells is necessary to obtain therapeutic cell populations for tissue engineering strategies. Currently, utilization of MSCs for adipose tissue engineering is limited due to the attenuation of their adipogenic differentiation potential following extensive ex vivo expansion on conventional tissue culture plastic (TCP) substrates. In the present study, the ability of a denatured collagen type I (DC) matrix to preserve MSC adipogenic potential during ex vivo expansion was examined. Adipocyte-related markers and functions were examined in vitro in response to adipogenic culture conditions for 21 days in comparison to early passage MSCs and late passage MSCs ex vivo expanded on TCP. The results demonstrated significant preservation of the ability of late passage MSCs ex vivo expanded on the DC matrix to express adipogenic markers (fatty acid-binding protein-4, lipoprotein lipase, acyl-CoA synthetase, adipsin, facilitative glucose transporter-4, and accumulation of lipids) similar to the early passage cells and in contrast to late passage MSCs expanded on TCP. The ability of the DC matrix to preserve adipocyte-related markers and functions of MSCs following extensive ex vivo expansion represents a novel culture technique to expand functional adipogenic progenitors for tissue engineering applications.
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PMID:Matrix-mediated retention of adipogenic differentiation potential by human adult bone marrow-derived mesenchymal stem cells during ex vivo expansion. 1591 65

To investigate the full range of molecular changes associated with erectile dysfunction (ED) in Type 1 diabetes, we examined alterations in penile gene expression in streptozotocin-induced diabetic rats and littermate controls. With the use of Affymetrix GeneChip arrays and statistical filtering, 529 genes/transcripts were considered to be differentially expressed in the diabetic rat cavernosum compared with control. Gene Ontology (GO) classification indicated that there was a decrease in numerous extracellular matrix genes (e.g., collagen and elastin related) and an increase in oxidative stress-associated genes in the diabetic rat cavernosum. In addition, PubMatrix literature mining identified differentially expressed genes previously shown to mediate vascular dysfunction [e.g., ceruloplasmin (Cp), lipoprotein lipase, and Cd36] as well as genes involved in the modulation of the smooth muscle phenotype (e.g., Kruppel-like factor 5 and chemokine C-X3-C motif ligand 1). Real-time PCR was used to confirm changes in expression for 23 relevant genes. Further validation of Cp expression in the diabetic rat cavernosum demonstrated increased mRNA levels of the secreted and anchored splice variants of Cp. CP protein levels showed a 1.9-fold increase in tissues from diabetic rats versus controls. Immunohistochemistry demonstrated localization of CP protein in cavernosal sinusoids of control and diabetic animals, including endothelial and smooth muscle layers. Overall, this study broadens the scope of candidate genes and pathways that may be relevant to the pathophysiology of diabetes-induced ED as well as highlights the potential complexity of this disorder.
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PMID:Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats. 1611 69

The presence of multiple cell types in bone marrow and their varying proportions from isolation to isolation may count for the considerable variation in the outcome of different experiments. The presence of these multiple subpopulations suggests a need for a method that can purify the osteogenic component, i.e. osteoprogenitors, from other components. The availabilities of monoclonal antibodies recognizing subpopulations of osteoblasts are providing means for antibody-based methods. The cell surface antigens STRO-1, ALP and HOP-26 were used for cell sorting experiments with fluorescence activated cell sorting (FACS). These cell populations were analyzed on differential gene expression, cell proliferation and differentiation into the osteoblastic lineage. The oligo-microarray results showed that only the ALP positive cell population expressed genes of the extracellular matrix; like different collagens, ECM-1 and matrix protease MMP-14. The real-time polymerase chain reaction (QPCR) results showed that STRO-1 and ALP positive cells had an upregulation in expression of lipoprotein lipase, osteocalcin, and collagen type I. Integrin beta-3 was only upregulated for ALP positive cells, while for these cells downregulation occurred for the genes myosine, alkaline phosphatase and integrin beta-1. HOP-26 positive cells showed an upregulation in collagen type I compared to control group. The DNA analysis revealed that the cells of the control group and the HOP-26 positive cells showed a 5 times higher cell growth compared to the STRO-1 and ALP positive cells. The alkaline phosphatase activity showed no activity for the control group. The STRO-1 and ALP positive cells had a higher activity compared to the HOP-26 positive. The calcium measurements revealed only for the control group calcium at day 24. Based on the results of our study, we conclude that the FACS method had no negative effect on the proliferating as well as differentiating response of the cells. Further, we conclude that by using an antibody-based cell selection method, different cell populations with different mRNA expression profiles and different osteogenic characteristics can be obtained.
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PMID:Enrichment of osteogenic cell populations from rat bone marrow stroma. 1696 17

Ectomesenchymal cells isolated from the first branchial arch have the potential to differentiate into a variety of cell lineages both in vitro and in vivo. This study was aimed to confirm the plasticity of multilineage differentiation with molecular and cellular characterization. Monolayer cultures of ectomesenchymal cells harvested from the first branchial arch primordia in embryonic day 9.5 BALB/c mice were passaged 3 times before analysis. Staining with antibodies against S-100, p75 and vimentin suggested that the population of stem cells originated from ectomesenchyme, with few contaminating cells stained for cytokeratin. Then, cells were transferred to adipogenic, osteogenic, chondrogenic and odontogenic media. The initiation of controlled differentiation was determined with histological assays, and the expression of tissue-specific genes was detected using immunocytochemical staining and reverse transcription polymerase chain reaction. The adipogenic ectomesenchymal cells showed accumulation of lipid vacuoles and expression of lipoprotein lipase and peroxisome proliferator-activated receptor gamma(2). Following osteoinduction, the fibroblast-like cells became cuboidal and formed mineralized nodules. In addition, the expression of mRNA encoding osteocalcin and osteopontin proved osteogenesis at the molecular level. Chondrogenic lineage expressed collagen type II, aggrecan and Sox9 with a low level of collagen type I in monolayer culture. Odontogenesis was determined by dentin sialophosphoprotein, collagen type I and dentin matrix protein 1 expression. Therefore, we have demonstrated that ectomesenchymal cells from the first branchial arch are capable of extensive multilineage differentiation in vitro, controllable by the culture environment. This makes them a relevant and valuable source of stem cells for research of craniofacial development and tissue engineering of restoration.
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PMID:Characterization of ectomesenchymal cells isolated from the first branchial arch during multilineage differentiation. 1710 83

Chondrocytes and adipocytes are two differentiated cell types which are both derived from mesenchymal cells. The purpose of this study was to investigate whether peroxisome proliferator-activated receptor-gamma (PPARgamma), a transcription factor involved in lineage determination during adipogenesis, is able to induce adipogenic differentiation in growth plate chondrocytes. Isolated epiphyseal chondrocytes were infected with a PPARgamma adenovirus or treated with the PPARgamma agonist ciglitazone. Both of these treatments resulted in lipid droplet accumulation and expression of the adipogenic markers aP2, lipoprotein lipase, and adipsin in chondrocytes. Proteoglycan matrix synthesis was decreased in the PPARgamma-infected cells, as was the expression of the chondrogenic genes Col2a1 and aggrecan. Growth plate cells transfected with a PPARgamma expression plasmid under the control of the collagen alpha1(II) promoter also demonstrated a similar adipogenic changes. Terminal differentiation of growth plate chondrocytes induced by thyroid hormone was also inhibited by overexpression of PPARgamma and ciglitazone treatment, with decreased expression of alkaline phosphatase and Runx2/Cbfa1 genes. These in vitro data suggest that PPARgamma is able to promote adipogenic differentiation in growth plate chondrocytes, while negatively regulating chondrogenic differentiation and terminal differentiation.
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PMID:Peroxisome Proliferator-Activated Receptor-gamma Promotes Adipogenic Changes in Growth Plate Chondrocytes In Vitro. 1725 68

Intracellular lipid accumulation (steatosis) and resultant lipotoxicity are key features of diabetic cardiomyopathy. Since cardiac hormone-sensitive lipase (HSL) is activated in diabetic mice, we sought to explore a pathophysiological function of cardiac HSL in the development of diabetic cardiomyopathy. Transgenic (Tg) mice with heart-specific HSL overexpression were generated, and cardiac histology, function, lipid profile, and gene expressions were analyzed after induction of diabetes by streptozotocin. Electron microscopy showed numerous lipid droplets in wild-type (Wt) hearts after 3 wk of diabetes, whereas Tg mice showed no lipid droplet accumulation. Cardiac content of acylglycerides was increased approximately 50% with diabetes in Wt mice, whereas this was blunted in Tg hearts. Cardiac lipid peroxide content was twofold lower in Tg hearts than in Wt hearts. The mRNA expressions for peroxisome proliferator-activated receptor-alpha, genes for triacylglycerol synthesis, and lipoprotein lipase were increased with diabetes in Wt hearts, whereas this induction was absent in Tg hearts. Expression of genes associated with lipoapoptosis was decreased, whereas antioxidant protein metallothioneins were increased in diabetic Tg hearts. Diabetic Wt hearts showed interstitial fibrosis and increased collagen content. However, Tg hearts displayed no overt fibrosis, concomitant with decreased expression of collagens, transforming growth factor-beta, and matrix metalloproteinase 2. Notably, mortality during the experimental period was approximately twofold lower in diabetic Tg mice compared with Wt mice. In conclusion, since HSL overexpression inhibits cardiac steatosis and fibrosis by apparently hydrolyzing toxic lipid metabolites, cardiac HSL could be a therapeutic target for regulating diabetic cardiomyopathy.
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PMID:Cardiac overexpression of hormone-sensitive lipase inhibits myocardial steatosis and fibrosis in streptozotocin diabetic mice. 1841 75

Electrospun 3-dimensional nanofibrous scaffolds share morphologic similarities to collagen fibrils, and promote favorable biologic responses of seeded cells. In this study, we have fabricated a 3-dimensional nanofibrous scaffold made of poly L-lactic acid, and examined its ability to support and maintain the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro. After a 21-day incubation, oil red O staining of constructs treated with adipogenic supplements revealed positive adipose-like staining, compared with lack of staining in untreated cultures. Semi-quantitative RT-PCR analysis of human bone marrow-derived mesenchymal stem cells cultured in adipogenic medium revealed highly elevated levels of adipogenesis-associated genes (1797-fold for lipoprotein lipase, and 5.6-fold for peroxisome proliferator-activated receptor gamma). Immunofluorescence staining of cellular constructs in adipogenic culture media showed the presence of lipoprotein lipase vesicles, a characteristic feature of adipose tissue. These results suggest that the poly L-lactic acid-based nanofibrous scaffold is a promising candidate for adult stem cell-based engineering of adipose tissue.
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PMID:In vitro adipose tissue engineering using an electrospun nanofibrous scaffold. 1894 88


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