GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Basigin Promotes Cardiac Fibrosis and Failure in Response to Chronic Pressure Overload in Mice
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 36, No. 4 ( 2016-04), p. 636-646
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. 4 ( 2016-04), p. 636-646
    Abstract: Basigin (Bsg) is a transmembrane glycoprotein that activates matrix metalloproteinases and promotes inflammation. However, the role of Bsg in the pathogenesis of cardiac hypertrophy and failure remains to be elucidated. We examined the role of Bsg in cardiac hypertrophy and failure in mice and humans. Approach and Results— We performed transverse aortic constriction in Bsg +/– and in wild-type mice. Bsg +/– mice showed significantly less heart and lung weight and cardiac interstitial fibrosis compared with littermate controls after transverse aortic constriction. Both matrix metalloproteinase activities and oxidative stress in loaded left ventricle were significantly less in Bsg +/– mice compared with controls. Echocardiography showed that Bsg +/– mice showed less hypertrophy, less left ventricular dilatation, and preserved left ventricular fractional shortening compared with littermate controls after transverse aortic constriction. Consistently, Bsg +/– mice showed a significantly improved long-term survival after transverse aortic constriction compared with Bsg +/+ mice, regardless of the source of bone marrow ( Bsg +/+ or Bsg +/– ). Conversely, cardiac-specific Bsg-overexpressing mice showed significantly poor survival compared with littermate controls. Next, we isolated cardiac fibroblasts and examined their responses to angiotensin II or mechanical stretch. Both stimuli significantly increased Bsg expression, cytokines/chemokines secretion, and extracellular signal–regulated kinase/Akt/JNK activities in Bsg +/+ cardiac fibroblasts, all of which were significantly less in Bsg +/– cardiac fibroblasts. Consistently, extracellular and intracellular Bsg significantly promoted cardiac fibroblast proliferation. Finally, serum levels of Bsg were significantly elevated in patients with heart failure and predicted poor prognosis. Conclusions— These results indicate the crucial roles of intracellular and extracellular Bsg in the pathogenesis of cardiac hypertrophy, fibrosis, and failure in mice and humans.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.115.306686
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1494427-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    SmgGDS as a Crucial Mediator of the Inhibitory Effects of Statins on Cardiac Hypertrophy and Fibrosis : Novel Mechanism of the Pleiotropic Effects of Statins
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Hypertension Vol. 67, No. 5 ( 2016-05), p. 878-889
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 67, No. 5 ( 2016-05), p. 878-889
    Abstract: The detailed molecular mechanisms of the pleiotropic effects of statins remain to be fully elucidated. Here, we hypothesized that cardioprotective effects of statins are mediated by small GTP-binding protein GDP dissociation stimulator (SmgGDS). SmgGDS +/– and wild-type (WT) mice were treated with continuous infusion of angiotensin II (Ang II) for 2 weeks with and without oral treatment with atorvastatin or pravastatin. At 2 weeks, the extents of Ang II–induced cardiac hypertrophy and fibrosis were comparable between the 2 genotypes. However, statins significantly attenuated cardiomyocyte hypertrophy and fibrosis in WT mice, but not in SmgGDS +/– mice. In SmgGDS +/– cardiac fibroblasts (CFs), Rac1 expression, extracellular signal–regulated kinases 1/2 activity, Rho-kinase activity, and inflammatory cytokines secretion in response to Ang II were significantly increased when compared with WT CFs. Atorvastatin significantly reduced Rac1 expression and oxidative stress in WT CFs, but not in SmgGDS +/– CFs. Furthermore, Bio-plex analysis revealed significant upregulations of inflammatory cytokines/chemokines and growth factors in SmgGDS +/– CFs when compared with WT CFs. Importantly, conditioned medium from SmgGDS +/– CFs increased B-type natriuretic peptide expression in rat cardiomyocytes to a greater extent than that from WT CFs. Furthermore, atorvastatin significantly increased SmgGDS secretion from mouse CFs. Finally, treatment with recombinant SmgGDS significantly reduced Rac1 expression in SmgGDS +/– CFs. These results indicate that both intracellular and extracellular SmgGDS play crucial roles in the inhibitory effects of statins on cardiac hypertrophy and fibrosis, partly through inhibition of Rac1, Rho kinase, and extracellular signal–regulated kinase 1/2 pathways, demonstrating the novel mechanism of the pleiotropic effects of statins.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.115.07089
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2094210-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    ROCK1 Plays a Crucial Role to Maintain Cardiac Function in Response to Pressure-Overload in Mice
    Elsevier BV ; 2015
    In:  Journal of Cardiac Failure Vol. 21, No. 10 ( 2015-10), p. S175-
    Details
    In: Journal of Cardiac Failure, Elsevier BV, Vol. 21, No. 10 ( 2015-10), p. S175-
    Type of Medium: Online Resource
    ISSN: 1071-9164
    URL: Article
    DOI: 10.1016/j.cardfail.2015.08.173
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 2048826-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Different Roles of Myocardial ROCK1 and ROCK2 in Response to Chronic Pressure-Overload in Mice
    Elsevier BV ; 2017
    In:  Journal of Cardiac Failure Vol. 23, No. 10 ( 2017-10), p. S14-
    Details
    In: Journal of Cardiac Failure, Elsevier BV, Vol. 23, No. 10 ( 2017-10), p. S14-
    Type of Medium: Online Resource
    ISSN: 1071-9164
    URL: Article
    DOI: 10.1016/j.cardfail.2017.08.066
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2048826-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Crucial Role of Rho-kinase in Pressure-overload-induced Right Ventricular Hypertrophy and Dysfunction in Mice
    Elsevier BV ; 2014
    In:  Journal of Cardiac Failure Vol. 20, No. 10 ( 2014-10), p. S144-
    Details
    In: Journal of Cardiac Failure, Elsevier BV, Vol. 20, No. 10 ( 2014-10), p. S144-
    Type of Medium: Online Resource
    ISSN: 1071-9164
    URL: Article
    DOI: 10.1016/j.cardfail.2014.07.085
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 2048826-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Different roles of myocardial ROCK1 and ROCK2 in cardiac dysfunction and postcapillary pulmonary hypertension in mice
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 30 ( 2018-07-24)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 30 ( 2018-07-24)
    Abstract: Although postcapillary pulmonary hypertension (PH) is an important prognostic factor for patients with heart failure (HF), its pathogenesis remains to be fully elucidated. To elucidate the different roles of Rho-kinase isoforms, ROCK1 and ROCK2, in cardiomyocytes in response to chronic pressure overload, we performed transverse aortic constriction (TAC) in cardiac-specific ROCK1-deficient ( cROCK1 −/− ) and ROCK2-deficient ( cROCK2 −/− ) mice. Cardiomyocyte-specific ROCK1 deficiency promoted pressure-overload-induced cardiac dysfunction and postcapillary PH, whereas cardiomyocyte-specific ROCK2 deficiency showed opposite results. Histological analysis showed that pressure-overload-induced cardiac hypertrophy and fibrosis were enhanced in cROCK1 −/− mice compared with controls, whereas cardiac hypertrophy was attenuated in cROCK2 −/− mice after TAC. Consistently, the levels of oxidative stress were up-regulated in cROCK1 −/− hearts and down-regulated in cROCK2 −/− hearts compared with controls after TAC. Furthermore, cyclophilin A (CyPA) and basigin (Bsg), both of which augment oxidative stress, enhanced cardiac dysfunction and postcapillary PH in cROCK1 −/− mice, whereas their expressions were significantly lower in cROCK2 −/− mice. In clinical studies, plasma levels of CyPA were significantly increased in HF patients and were higher in patients with postcapillary PH compared with those without it. Finally, high-throughput screening demonstrated that celastrol, an antioxidant and antiinflammatory agent, reduced the expressions of CyPA and Bsg in the heart and the lung, ameliorating cardiac dysfunction and postcapillary PH induced by TAC. Thus, by differentially affecting CyPA and Bsg expressions, ROCK1 protects and ROCK2 jeopardizes the heart from pressure-overload HF with postcapillary PH, for which celastrol may be a promising agent.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1721298115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Abstract 12523: Crucial Role of SmgGDS in the Inhibitory Effects of Statins on Cardiac Hypertrophy and Fibrosis in Mice
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Circulation Vol. 130, No. suppl_2 ( 2014-11-25)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. suppl_2 ( 2014-11-25)
    Abstract: Introduction: We have previously demonstrated that small GTP-binding protein dissociation stimulator (SmgGDS) plays a crucial role in the pleiotropic effects of HMG-CoA reductase inhibitors (statins) in mice and humans. In the present study, we tested our hypothesis that SmgGDS plays a crucial role in the inhibitory effects of statins on the development of cardiac hypertrophy and fibrosis. Methods & Results: We administered angiotensin II (AngII, 2 mg/kg/day, 2 weeks) to SmgGDS-deficient ( SmgGDS +/- ) mice and littermate controls ( SmgGDS +/+ ), which were orally treated with either statins (atorvastatin 10 mg/kg/day or pravastatin 50 mg/kg/day, n=10 each group) or vehicle. AngII equally elevated systolic blood pressure and promoted cardiac hypertrophy and fibrosis in SmgGDS +/+ and SmgGDS +/- . Both statins significantly reduced LV wall thickness, cardiac myocyte cross-sectional area, and fibrotic area in AngII-infused SmgGDS +/+ mice (all P 〈 0.01). In contrast, the inhibitory effects of statins were absent in AngII-infused SmgGDS +/- mice. Additionally, statins significantly improved LV diastolic function (E/A) in SmgGDS +/+ mice (P 〈 0.01) but not in SmgGDS +/- mice. Interestingly, immunostaining revealed that SmgGDS was highly expressed in cardiac fibroblasts (CFs) in the heart of AngII-infused SmgGDS +/+ mice. Then, we harvested CFs from SmgGDS +/+ and SmgGDS +/- mice and stimulated them with AngII with or without statins. At baseline, SmgGDS +/- CFs showed significant increase in Rac1 expression (1.8-fold), ERK1/2 activity (4.0-fold), Rho-kinase activity (phospho-MYPT/total-MYPT, 1.4-fold) compared to SmgGDS +/+ CFs, whereas Akt activity was significantly less in SmgGDS +/- CFs compared to SmgGDS +/+ CFs (n=4, all P 〈 0.05). Statin treatment significantly reduced Rac1 expression in SmgGDS +/+ CFs (-30%, n=4, P 〈 0.05), which was not observed in SmgGDS +/- CFs, suggesting that SmgGDS mediates the inhibitory effects of statins on Rac1 signaling. Conclusions: These results indicate that SmgGDS plays a crucial role in the inhibitory effects of statins on cardiac hypertrophy and fibrosis, partly through inhibition of Rac1, Rho-kinase, and ERK1/2 pathways.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.130.suppl_2.12523
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1466401-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Abstract 541: SmgGDS as a Crucial Mediator of the Inhibitory Effects of Statins on Cardiac Hypertrophy and Fibrosis -Novel Mechanism of the Pleiotropic Effects of Statins-
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 35, No. suppl_1 ( 2015-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. suppl_1 ( 2015-05)
    Abstract: Background: Statins are widely known to exert beneficial pleiotropic effects mediated by anti-oxidative and anti-inflammatory mechanisms, independent of their LDL-cholesterol lowering effect. However, the detailed molecular mechanisms of the pleiotropic effects of statins remain to be fully elucidated. Here, we demonstrate that small GTP-binding protein GDP dissociation stimulator (SmgGDS) is a crucial mediator of the pleiotropic effects of statins. Methods and Results: SmgGDS +/- and wild-type (WT) mice were treated with continuous infusion of angiotensin II (AngII) for 2 weeks with and without oral treatment with atorvastatin (10 mg/kg/day) or pravastatin (50 mg/kg/day). At 2 weeks, the extents of AngII-induced cardiac hypertrophy and fibrosis were comparable between the 2 genotypes. However, statins significantly attenuated cardiomyocyte hypertrophy, fibrosis and left ventricular diastolic dysfunction in WT mice, but not in SmgGDS +/- mice. Since SmgGDS was highly expressed in cardiac fibroblasts (CFs) in the heart, we then examined the role of SmgGDS in cultured CFs from WT and SmgGDS +/- mice. In SmgGDS +/- CFs, Rac1 expression, ERK1/2 activity, Rho-kinase activity and inflammatory cytokines secretion in response to AngII were significantly increased as compared with WT CFs. Atorvastatin significantly reduced Rac1 expression and oxidative stress in WT CFs, but not in SmgGDS +/- CFs. Furthermore, Bio-plex analysis revealed significant up-regulations of inflammatory cytokines/chemokines and growth factors in SmgGDS +/- CFs as compared with WT CFs. Importantly, conditioned medium from SmgGDS +/- CFs increased BNP expression in neonatal rat cardiomyocytes to a greater extent than that from WT CFs. Furthermore, atorvastatin significantly increased SmgGDS secretion from mouse and human CFs. Finally, treatment with recombinant SmgGDS significantly reduced Rac1 expression in SmgGDS +/- CFs. Conclusion: These results indicate that both intracellular and extracellular SmgGDS play a crucial role in the inhibitory effects of statins on cardiac hypertrophy and fibrosis, partly through inhibition of Rac1, Rho-kinase and ERK1/2 pathways, demonstrating the novel mechanism of the pleiotropic effects of statins.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.35.suppl_1.541
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1494427-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Abstract 533: Crucial Role of Rho-Kinase in Pressure Overload--Induced Right Ventricular Hypertrophy and Dysfunction in Mice: A Possible Novel Therapeutic Target of Right Ventricular Failure
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 34, No. suppl_1 ( 2014-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. suppl_1 ( 2014-05)
    Abstract: Rationale: Right ventricular (RV) failure is the leading cause of death in various cardiopulmonary diseases, including pulmonary hypertension. It is generally considered that the RV is vulnerable to pressure-overload as compared with the left ventricle (LV). However, as compared with LV failure, the molecular mechanisms of RV failure are poorly understood. Objective: We aimed to identify molecular therapeutic targets for RV failure in a mouse model of pressure-overload. Methods and Results: To induce pressure-overload to respective ventricles, we performed pulmonary artery constriction (PAC) or transverse aortic constriction (TAC) in mice. We first performed microarray analysis and found that the molecules related to RhoA/Rho-kinase and integrin pathways were significantly up-regulated in the RV with PAC compared with the LV with TAC. Then, we examined the responses of both ventricles to chronic pressure-overload in vivo. We demonstrated that compared with TAC, PAC caused greater extents of mortality, Rho-kinase expression (especially ROCK2 isoform) and oxidative stress in pressure-overloaded RV, reflecting the weakness of the RV in response to pressure-overload. Additionally, mechanical stretch of RV cardiomyocytes from rats immediately up-regulated ROCK2 expression (not ROCK1), suggesting the specific importance of ROCK2 in stretch-induced responses of RV tissues. Furthermore, mice with myocardial-specific overexpression of dominant-negative Rho-kinase (DN-RhoK) showed resistance to pressure-overload-induced hypertrophy and dysfunction associated with reduced oxidative stress. Finally, DN-RhoK mice showed a significantly improved long-term survival in both PAC and TAC as compared with littermate controls. Conclusions: These results indicate that the Rho-kinase pathway plays a crucial role in RV hypertrophy and dysfunction, suggesting that the pathway is a novel therapeutic target of RV failure in humans.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.34.suppl_1.533
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1494427-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Identification of Adipsin as a Novel Prognostic Biomarker in Patients With Coronary Artery Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Journal of the American Heart Association Vol. 8, No. 23 ( 2019-12-03)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 23 ( 2019-12-03)
    Abstract: Circulating proteins are exposed to vascular endothelial layer and influence their functions. Among them, adipsin is a member of the trypsin family of peptidases and is mainly secreted from adipocytes, monocytes, and macrophages, catalyzing the rate‐limiting step of the alternative complement pathway. However, its pathophysiological role in cardiovascular disease remains to be elucidated. Here, we examined whether serum adipsin levels have a prognostic impact in patients with coronary artery disease. Methods and Results In 370 consecutive patients undergoing diagnostic coronary angiography, we performed a cytokine array analysis for screening serum levels of 50 cytokines/chemokines and growth factors. Among them, classification and regression analysis identified adipsin as the best biomarker for prediction of their long‐term prognosis (median 71 months; interquartile range, 55–81 months). Kaplan–Meier curve showed that higher adipsin levels (≥400 ng/ mL ) were significantly associated with all‐cause death (hazard ratio [HR], 4.2; 95% CI, 1.7–10.6 [ P 〈 0.001]) and rehospitalization ( HR , 2.4; 95% CI, 1.7–3.5 [ P 〈 0.001]). Interestingly, higher high‐sensitivity C‐reactive protein levels (≥1 mg/L) were significantly correlated with all‐cause death ( HR, 3.2; 95% CI, 1.7–5.9 [ P 〈 0.001]) and rehospitalization ( HR, 1.5, 95% CI, 1.1–1.9 [ P 〈 0.01]). Importantly, the combination of adipsin (≥400 ng/ mL ) and high‐sensitivity C‐reactive protein (≥1 mg/L) was more significantly associated with all‐cause death ( HR, 21.0; 95% CI, 2.9–154.1 [ P 〈 0.001]). Finally, the receiver operating characteristic curve demonstrated that serum adipsin levels predict the death caused by acute myocardial infarction in patients with coronary artery disease (C‐statistic, 0.847). Conclusions These results indicate that adipsin is a novel biomarker that predicts all‐cause death and rehospitalization in patients with coronary artery disease, demonstrating the novel aspects of the alternative complementary system in the pathogenesis of coronary artery disease.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.119.013716
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2653953-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...