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  • American Physiological Society  (18)
  • Biology  (18)
  • 1
    Online Resource
    Online Resource
    Electromagnetic fields enhance chondrogenesis of human adipose-derived stem cells in a chondrogenic microenvironment in vitro
    American Physiological Society ; 2013
    In:  Journal of Applied Physiology Vol. 114, No. 5 ( 2013-03-01), p. 647-655
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 114, No. 5 ( 2013-03-01), p. 647-655
    Abstract: We tested the hypothesis that electromagnetic field (EMF) stimulation enhances chondrogenesis in human adipose-derived stem cells (ADSCs) in a chondrogenic microenvironment. A two-dimensional hyaluronan (HA)-coated well (2D-HA) and a three-dimensional pellet culture system (3D-pellet) were used as chondrogenic microenvironments. The ADSCs were cultured in 2D-HA or 3D-pellet, and then treated with clinical-use pulse electromagnetic field (PEMF) or the innovative single-pulse electromagnetic field (SPEMF) stimulation. The cytotoxicity, cell viability, and chondrogenic and osteogenic differentiations were analyzed after PEMF or SPEMF treatment. The modules of PEMF and SPEMF stimulations used in this study did not cause cytotoxicity or alter cell viability in ADSCs. Both PEMF and SPEMF enhanced the chondrogenic gene expression (SOX-9, collagen type II, and aggrecan) of ADSCs cultured in 2D-HA and 3D-pellet. The expressions of bone matrix genes (osteocalcin and collagen type I) of ADSCs were not changed after SPEMF treatment in 2D-HA and 3D-pellet; however, they were enhanced by PEMF treatment. Both PEMF and SPEMF increased the cartilaginous matrix (sulfated glycosaminoglycan) deposition of ADSCs. However, PEMF treatment also increased mineralization of ADSCs, but SPEMF treatment did not. Both PEMF and SPEMF enhanced chondrogenic differentiation of ADSCs cultured in a chondrogenic microenvironment. SPEMF treatment enhanced ADSC chondrogenesis, but not osteogenesis, when the cells were cultured in a chondrogenic microenvironment. However, PEMF enhanced both osteogenesis and chondrogenesis under the same conditions. Thus the combination of a chondrogenic microenvironment with SPEMF stimulation can promote chondrogenic differentiation of ADSCs and may be applicable to articular cartilage tissue engineering.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.01216.2012
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2013
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 2
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    Online Resource
    Cellular distribution of GPR14 and the positive inotropic role of urotensin II in the myocardium in adult rat
    American Physiological Society ; 2004
    In:  Journal of Applied Physiology Vol. 97, No. 6 ( 2004-12), p. 2228-2235
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 97, No. 6 ( 2004-12), p. 2228-2235
    Abstract: Urotensin II is a cyclic neuropeptide recently shown to play a role via its receptor GPR14 in regulating vascular tone in the mammalian cardiovascular system. The existence of GPR14 in rat heart has been validated by ligand binding assay and RT-PCR. In the present study, we investigated the cellular distribution of GPR14 protein in rat heart by using immunohistochemistry and confocal microscopic immunofluorescence double staining with antipeptide polyclonal antibodies against GPR14 and cell type markers for myocytes and endothelial cells. The direct effect of urotensin II on left ventricular contractility was further evaluated in isolated left ventricular papillary muscles of the rat. In paraffin-embedded heart sections, positive immunohistochemical staining was observed in the left ventricle but not in the right ventricle and atria. Immunofluorescence double staining revealed the cardiac myocyte as the only cell type expressing GPR14 protein in frozen heart sections as well as in isolated cardiac myocytes. There was no visible signal for GPR14 in intramyocardial coronary arteries and capillaries. The existence of GPR14 protein in rat heart was further validated by immunoprecipitation and Western blot analysis. In isolated rat left ventricular papillary muscle preparations, urotensin II induced an increase in active contractile force. GPR14 mRNA was also detected in rat heart by RT-PCR. These data provide the first direct evidence for the cellular localization of GPR14 receptor protein and a positive inotropic effect of urotensin II in normal rat heart.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.00540.2004
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2004
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 3
    Online Resource
    Online Resource
    Hyaluronan initiates chondrogenesis mainly via CD44 in human adipose-derived stem cells
    American Physiological Society ; 2013
    In:  Journal of Applied Physiology Vol. 114, No. 11 ( 2013-06-01), p. 1610-1618
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 114, No. 11 ( 2013-06-01), p. 1610-1618
    Abstract: Cell-matrix adhesion is one of the important interactions that regulates stem cell survival, self-renewal, and differentiation. Our previous report (Wu SC, Chang JK, Wang CK, Wang GJ, Ho ML. Biomaterials 31: 631–640, 2010) indicated that a microenvironment enriched with hyaluronan (HA) initiated and enhanced chondrogenesis in human adipose-derived stem cells (hADSCs). We further hypothesize that HA-induced chondrogenesis in hADSCs is mainly due to the interaction of HA and CD44 (HA-CD44), a cell surface receptor of HA. The HA-CD44 interaction was tested by examining the mRNA expression of hyaluronidase-1 (Hyal-1) and chondrogenic marker genes (SOX-9, collagen type II, and aggrecan) in hADSCs cultured on HA-coated wells. Cartilaginous matrix formation, sulfated glycosaminoglycan, and collagen productions by hADSCs affected by HA-CD44 interaction were tested in a three-dimensional fibrin hydrogel. About 99.9% of hADSCs possess CD44. The mRNA expressions of Hyal-1 and chondrogenic marker genes were upregulated by HA in hADSCs on HA-coated wells. Blocking HA-CD44 interaction by anti-CD44 antibody completely inhibited Hyal-1 expression and reduced chondrogenic marker gene expression, which indicates that HA-induced chondrogenesis in hADSCs mainly acts through HA-CD44 interaction. A 2-h preincubation and coculture of cells with HA in hydrogel (HA/fibrin hydrogel) not only assisted in hADSC survival, but also enhanced expression of Hyal-1 and chondrogenic marker genes. Higher levels of sulfated glycosaminoglycan and total collagen were also found in HA/fibrin hydrogel group. Immunocytochemistry showed more collagen type II, but less collagen type X, in HA/fibrin than in fibrin hydrogels. Our results indicate that signaling triggered by HA-CD44 interaction significantly contributes to HA-induced chondrogenesis and may be applied to adipose-derived stem cell-based cartilage regeneration.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.01132.2012
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2013
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 4
    Online Resource
    Online Resource
    Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 295, No. 6 ( 2008-12), p. H2399-H2408
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 295, No. 6 ( 2008-12), p. H2399-H2408
    Abstract: The objective of this study was to determine the effects and mechanisms of serum amyloid A (SAA) on coronary endothelial function. Porcine coronary arteries and human coronary arterial endothelial cells (HCAECs) were treated with SAA (0, 1, 10, or 25 μg/ml). Vasomotor reactivity was studied using a myograph tension system. SAA significantly reduced endothelium-dependent vasorelaxation of porcine coronary arteries in response to bradykinin in a concentration-dependent manner. SAA significantly decreased endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein levels as well as NO bioavailability, whereas it increased ROS in both artery rings and HCAECs. In addition, the activities of internal antioxidant enzymes catalase and SOD were decreased in SAA-treated HCAECs. Bio-plex immunoassay analysis showed the activation of JNK, ERK2, and IκB-α after SAA treatment. Consequently, the antioxidants seleno-l-methionine and Mn(III) tetrakis-(4-benzoic acid)porphyrin and specific inhibitors for JNK and ERK1/2 effectively blocked the SAA-induced eNOS mRNA decrease and SAA-induced decrease in endothelium-dependent vasorelaxation in porcine coronary arteries. Thus, SAA at clinically relevant concentrations causes endothelial dysfunction in both porcine coronary arteries and HCAECs through molecular mechanisms involving eNOS downregulation, oxidative stress, and activation of JNK and ERK1/2 as well as NF-κB. These findings suggest that SAA may contribute to the progress of coronary artery disease.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00238.2008
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Lactosylceramide promotes cell migration and proliferation through activation of ERK1/2 in human aortic smooth muscle cells
    American Physiological Society ; 2009
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 297, No. 1 ( 2009-07), p. H400-H408
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 297, No. 1 ( 2009-07), p. H400-H408
    Abstract: Increased plasma levels of lactosylceramide (LacCer) have been associated with cardiovascular disease. However, it is largely unknown whether LacCer directly contributes to dysfunction of smooth muscle cells (SMCs), a key event in vascular lesion formation. In the present study, we determined the effects and potential mechanisms of LacCer on cell migration and proliferation in human aortic SMCs (AoSMCs). Cell migration and proliferation were determined by a modified Boyden chamber assay and nonradioactive colorimetric (MTS) assay, respectively. We found that LacCer significantly induced AoSMC migration and proliferation in a concentration- and time-dependent manner. In addition, LacCer significantly upregulated the expression of PDGFR-B, integrins (α v and β 3 ), and matrix metalloproteinases (matrix metalloproteinase-1 and -2) at both mRNA and protein levels, as determined by real-time PCR and Western blot analyses, respectively. Furthermore, LacCer increased superoxide anion production and the transient phosphorylation of ERK1/2 in AoSMCs, as determined by dihydroethidium staining and immunoassay, respectively. Accordingly, LacCer-induced cell migration and proliferation were effectively blocked by antioxidants (seleno-l-methionine and Mn tetrakis porphyrin) and by a specific ERK1/2 inhibitor. Thus, LacCer promotes cell migration and proliferation through oxidative stress and activation of ERK1/2 in AoSMCs. These findings demonstrate the functional role of LacCer in the vascular disease pathogenesis.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.01254.2008
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2009
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 6
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    Online Resource
    Role of PKC in the novel synergistic action of urotensin II and angiotensin II and in urotensin II-induced vasoconstriction
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 292, No. 1 ( 2007-01), p. H348-H359
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 292, No. 1 ( 2007-01), p. H348-H359
    Abstract: The intracellular signaling of human urotensin II (hU-II) and its interaction with other vasoconstrictors such as ANG II are poorly understood. In endothelium-denuded rat aorta, coadministration of hU-II (1 nM) and ANG II (2 nM) exerted a significant contractile effect that was associated with increased protein kinase C (PKC) activity and phosphorylation of PKC-α/βII and myosin light chain, whereas either hU-II or ANG II administered alone at these concentrations had no statistically significant effect. This synergistic effect was abrogated by the PKC inhibitor chelerythrine (10 and 30 μM), the selective PKC-α/βII inhibitor Gö-6976 (0.1 and 1 μM), the hU-II receptor ligand urantide (30 nM and 1 μM), or the ANG II antagonist losartan (1 μM). Moreover, in endothelium-intact rat aorta, the synergistic effect of hU-II and ANG II was not exerted any longer, and this synergistic effect was unmasked by pretreatment of the nitric oxide synthase inhibitor N G -nitro-l-arginine methyl ester. hU-II (10 nM) alone caused a long-lasting increase in phospho-PKC-θ, phospho-myosin light chain, and PKC activity, which was associated with long-lasting vasoconstriction. These changes were prevented by chelerythrine. Methoxyverapamil-thapsigargin treatment reduced the hU-II-induced vasoconstriction by ∼50%. The methoxyverapamil-thapsigargin-resistant component of hU-II-induced vasoconstriction was dose-dependently inhibited by chelerythrine. In conclusion, hU-II induces a novel PKC-dependent synergistic action with ANG II in inducing vasoconstriction. PKC-α/βII is probably the PKC isoform involved in this synergistic action. Nitric oxide produced in the endothelium probably masks this synergistic action. The long-lasting vasoconstriction induced by hU-II alone is PKC dependent and associated with PKC-θ phosphorylation.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00512.2006
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 7
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    Online Resource
    Injection of autologous bone marrow cells in hyaluronan hydrogel improves cardiac performance after infarction in pigs
    American Physiological Society ; 2014
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 306, No. 7 ( 2014-04-01), p. H1078-H1086
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 306, No. 7 ( 2014-04-01), p. H1078-H1086
    Abstract: Intramyocardial injection of bone marrow mononuclear cells (MNCs) with hyaluronan (HA) hydrogel is beneficial to the ischemic heart in a rat model of myocardial infarction (MI). However, the therapeutic efficacy and safety must be addressed in large animals before moving onto a clinical trial. Therefore, the effect of combined treatment on MI was investigated in pigs. Coronary artery ligation was performed in minipigs to induce MI followed by an intramyocardial injection of normal saline ( n = 7), HA ( n = 7), normal saline with 1 × 10 8 freshly isolated MNCs ( n = 8), or HA with 1 × 10 8 MNCs (HA-MNC; n = 7), with a sham-operated group serving as a control ( n = 7). The response of each experimental group was estimated by echocardiography, ventricular catheterization, and histological analysis. Although injection of HA or MNCs slightly elevated left ventricular ejection fraction, the combined HA-MNC injection showed a significant increase in left ventricular ejection fraction, contractility, infarct size, and neovascularization. Importantly, injection of MNCs with HA also promoted MNC retention and MNC differentiation into vascular lineage cells in pigs. Therefore, this study not only provides evidence but also raises the possibility of using a combined HA-MNC injection as a promising therapy for heart repair.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00801.2013
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2014
    detail.hit.zdb_id: 1477308-9
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  • 8
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    Online Resource
    Prediction of atherosclerotic plaque ruptures with high-frequency ultrasound imaging and serum inflammatory markers
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 293, No. 5 ( 2007-11), p. H2836-H2844
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 293, No. 5 ( 2007-11), p. H2836-H2844
    Abstract: Atherosclerotic plaque rupture and thrombosis are the main causes of acute coronary syndrome. In the present study, we investigated whether ultrasound imaging and inflammatory parameters are predictive of plaque rupture in a newly established animal model. We developed a rabbit model for plaque rupture by locally delivering recombinant p53 adenovirus to plaques in rabbits fed a high-cholesterol diet for 10 wk, and plaque rupture was triggered using Chinese Russell's viper venom and histamine. We found that 81.1% of rabbits transfected with p53 ( n = 37) had the ruptured plaques, which was significantly higher than results in rabbits transfected with the control vector (26.3%, n = 38; P 〈 0.001). Among measured biomarkers, high-sensitive C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were significantly different between rabbits with and without ruptured plaques. Using high-frequency duplex and intravascular ultrasound imaging techniques, we obtained a list of parameters. With the multivariate logistic regression model, we identified that plaque eccentric index, plaque area, high-sensitive C-reactive protein, and corrected integrated backscatter intensity were significant predictors of plaque rupture, with odds ratios of 7.056 [95% confidence interval (CI): 1.958, ∼25.430], 1.942 (95% CI: 1.058, ∼3.564), 1.025 (95% CI: 1.007, ∼1.043), and 0.856 (95% CI: 0.775, ∼0.946), respectively. Localized p53 overexpression technique induces plaque rupture, and the combined measurement of ultrasound and biochemical markers is a valuable tool in predicting plaque rupture.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00472.2007
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 9
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    Online Resource
    Growth-related oncogene-α induces endothelial dysfunction through oxidative stress and downregulation of eNOS in porcine coronary arteries
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 293, No. 5 ( 2007-11), p. H3088-H3095
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 293, No. 5 ( 2007-11), p. H3088-H3095
    Abstract: Growth-related oncogene-α (GRO-α) is a member of the CXC chemokine family, which is involved in the inflammatory process including atherosclerosis. We hypothesized that GRO-α may affect endothelial functions in both porcine coronary arteries and human coronary artery endothelial cells (HCAECs). Vasomotor function was analyzed in response to thromboxane A2 analog U-46619 for contraction, bradykinin for endothelium-dependent vasorelaxation, and sodium nitroprusside (SNP) for endothelium-independent vasorelaxation. In response to 10 −6 M bradykinin, GRO-α (50 and 100 ng/ml) significantly reduced endothelium-dependent vasorelaxation by 34.73 and 48.8%, respectively, compared with controls ( P 〈 0.05). There were no changes in response to U-46619 or SNP between treated and control groups. With the lucigenin-enhanced chemiluminescence assay, superoxide anion production in GRO-α-treated vessels (50 and 100 ng/ml) was significantly increased by 50 and 86%, respectively, compared with controls ( P 〈 0.05). With real-time PCR analysis, endothelial nitric oxide synthase (eNOS) mRNA levels in porcine coronary arteries and HCAECs after GRO-α treatment were significantly decreased compared with controls ( P 〈 0.05). The eNOS protein levels by both immunohistochemistry and Western blot analyses were also decreased in GRO-α-treated vessels. Antioxidant seleno-l-methionine and anti-GRO-α antibody effectively blocked these effects of GRO-α on both porcine coronary arteries and HCAECs. In addition, GRO-α immunoreactivity was substantially increased in the atherosclerotic regions compared with nonatherosclerotic regions in human coronary arteries. Thus GRO-α impairs endothelium-dependent vasorelaxation in porcine coronary arteries through a mechanism of overproduction of superoxide anion and downregulation of eNOS. GRO-α may contribute to human coronary artery disease.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00473.2007
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 10
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    Online Resource
    The scar neovasculature after myocardial infarction in rats
    American Physiological Society ; 2005
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 289, No. 1 ( 2005-07), p. H108-H113
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 289, No. 1 ( 2005-07), p. H108-H113
    Abstract: A series of novel techniques, adapted from the field of tumor biology, were developed to quantify vascular structure and function and to explore the role of ANG II receptor AT1 in cardiac remodeling after myocardial infarction (MI). We examined the scar neovasculature at 1–4 wk post-MI in Sprague-Dawley rats with a view toward its ability to deliver and exchange oxygen. CD31 and DiOC 7 ( 3 ) staining was used to visualize anatomical vessels vs. those perfused. EF5/Cy3 immunohistochemical staining was used to quantify tissue hypoxia. We compared untreated controls with rats treated with losartan, an AT1 receptor antagonist. Our findings indicated that, at the infarct site, there was not only a 42–75% (1–4 wk post-MI) decrease in the number of anatomical vessels compared with controls but also a decrease in the fraction of perfused vessels from 70% in normal coronary vasculature to 48% at the infarct site. These changes were accompanied by progressive increases in diffusion distance and tissue hypoxia (100% increase in EF5/Cy3 staining at 4 wk post-MI). Losartan-treated rats exhibited a significantly less marked reduction in vascular perfusion and a significantly lesser extent of tissue hypoxia. Over the course of 4 wk post-MI, there is a reduction in coronary vasculature at the infarct site, the extent of which is attenuated by losartan. These findings implicate AT1 receptor upregulation, and perhaps angiotensin-related peptides, as being antiangiogenic.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00001.2005
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2005
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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