| 1. |
- Dalen, Magnus, et al.
(författare)
-
Percutaneous Fluoroscopic-Guided Endomyocardial Delivery in an Experimental Model of Left Ventricular Assist Device Support
- 2015
-
Ingår i: Journal of Cardiovascular Translational Research. - : Springer Science and Business Media LLC. - 1937-5387 .- 1937-5395. ; 8:6, s. 381-384
-
Tidskriftsartikel (refereegranskat)abstract
- Endomyocardial delivery in the setting of active left ventricular assist device (LVAD) support has rarely been studied. The objective was to establish a protocol for endomyocardial injections during LVAD support without compromising mechanical circulation. LVAD implantation was performed in four pigs. A curved needle catheter was percutaneously inserted into the right carotid artery and positioned into the left ventricle under fluoroscopic guidance. In the setting of increasing LVAD flows (2.3-3.1 l/min), percutaneous methylene blue dye administration into the myocardium proceeded without complications in all pigs. Transection of excised hearts revealed an anterior, lateral, inferior, and septal wall distribution of methylene blue documenting injections in all four regions of the left ventricle. Ex vivo, the catheter could be maneuvered close to the LVAD inflow cannula despite augmentation of LVAD flow up to 5 l/min. Endomyocardial injections during LVAD support was found to be feasible and safe with the curved needle catheter.
|
|
| 2. |
- Dieterich, L. C., et al.
(författare)
-
alphaB-Crystallin regulates expansion of CD11b(+)Gr-1(+) immature myeloid cells during tumor progression
- 2013
-
Ingår i: The FASEB Journal. - : FASEB. - 0892-6638 .- 1530-6860. ; 27:1, s. 151-62
-
Tidskriftsartikel (refereegranskat)abstract
- The molecular chaperone alphaB-crystallin has emerged as a target for cancer therapy due to its expression in human tumors and its role in regulating tumor angiogenesis. alphaB-crystallin also reduces neuroinflammation, but its role in other inflammatory conditions has not been investigated. Here, we examined whether alphaB-crystallin regulates inflammation associated with tumors and ischemia. We found that CD45(+) leukocyte infiltration is 3-fold increased in tumors and ischemic myocardium in alphaB-crystallin-deficient mice. Notably, alphaB-crystallin is prominently expressed in CD11b(+) Gr-1(+) immature myeloid cells (IMCs), known as regulators of angiogenesis and immune responses, while lymphocytes and mature granulocytes show low alphaB-crystallin expression. alphaB-Crystallin deficiency results in a 3-fold higher accumulation of CD11b(+) Gr-1(+) IMCs in tumors and a significant rise in CD11b(+) Gr-1(+) IMCs in spleen and bone marrow. Similarly, we noted a 2-fold increase in CD11b(+) Gr-1(+) IMCs in chronically inflamed livers in alphaB-crystallin-deficient mice. The effect of alphaB-crystallin on IMC accumulation is limited to pathological conditions, as CD11b(+) Gr-1(+) IMCs are not elevated in naive mice. Through ex vivo differentiation of CD11b(+) Gr-1(+) cells, we provide evidence that alphaB-crystallin regulates systemic expansion of IMCs through a cell-intrinsic mechanism. Our study suggests a key role of alphaB-crystallin in limiting expansion of CD11b(+) Gr-1(+) IMCs in diverse pathological conditions.
|
|
| 3. |
|
|
| 4. |
- Dimberg, Anna, et al.
(författare)
-
alphaB-crystallin promotes tumor angiogenesis by increasing vascular survival during tube morphogenesis
- 2008
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:4, s. 2015-2023
-
Tidskriftsartikel (refereegranskat)abstract
- Selective targeting of endothelial cells in tumor vessels requires delineation of key molecular events in formation and survival of blood vessels within the tumor microenvironment. To this end, proteins transiently up-regulated during vessel morphogenesis were screened for their potential as targets in antiangiogenic tumor therapy. The molecular chaperone alpha B-crystallin was identified as specifically induced with regard to expression level, modification by serine phosphorylation, and subcellular localization during tubular morphogenesis of endothelial cells. Small interfering RNA-mediated knockdown of alpha B-crystallin expression did not affect endothelial proliferation but led to attenuated tubular morphogenesis, early activation of proapoptotic caspase-3, and increased apoptosis. alpha B-crystallin was expressed in a subset of human tumor vessels but not in normal capillaries. Tumors grown in alpha B-crystallin(-/-) mice were significantly less vascularized than wild-type tumors and displayed increased areas of apoptosis/necrosis. Importantly, tumor vessels in alpha B-crystallin(-/-) mice were leaky and showed signs of caspase-3 activation and extensive apoptosis. Ultrastructural analyses showed defective vessels partially devoid of endothelial lining. These data strongly implicate alpha B-crystallin as an important regulator of tubular morphogenesis and survival of endothelial cell during tumor angiogenesis. Hereby we identify the small heat shock protein family as a novel class of anglogenic modulators.
|
|
| 5. |
|
|
| 6. |
- Matsumoto, Taro, et al.
(författare)
-
Ninein Is Expressed in the Cytoplasm of Angiogenic Tip-Cells and Regulates Tubular Morphogenesis of Endothelial Cells
- 2008
-
Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 28, s. 2123-2130
-
Tidskriftsartikel (refereegranskat)abstract
- Objective— Angiogenesis is an integral part of many physiologicalprocesses but may also aggravate pathological conditions suchas cancer. Development of effective angiogenesis inhibitorsrequires a thorough understanding of the molecular mechanismsregulating vessel formation. The aim of this project was toidentify proteins that regulate tubular morphogenesis of endothelialcells.Methods and Results— Phosphotyrosine-dependent affinity-purificationand mass spectrometry showed tyrosine phosphorylation of nineinduring tubular morphogenesis of endothelial cells. Ninein wasrecently identified as a centrosomal microtubule-anchoring protein.Our results show that ninein is localized in the cytoplasm inendothelial cells, and that it is highly expressed in the vasculaturein normal and pathological human tissues. Using embryoid bodiesas a model of vascular development, we found that ninein isabundantly expressed in the cytoplasm of endothelial cells duringsprouting angiogenesis, in particular in the sprouting tip-cell.In accordance, siRNA-dependent silencing of ninein in endothelialcells inhibited tubular morphogenesis.Conclusions— In this study, we show that ninein is expressedin developing vessels and in endothelial tip cells, and thatninein is critical for formation of the vascular tube. Thesedata strongly implicate ninein as an important new regulatorof angiogenesis.Proteins orchestrating morphological changes accompanying formationof the vascular tube constitute new targets for antiangiogenictherapy. In this study, we identify the microtubule-anchoringprotein ninein as an important new regulator of tubular morphogenesisof endothelial cells. This is the first report of a functionalrole of ninein in angiogenesis.
|
|
| 7. |
|
|
| 8. |
- Schiller, Petter, et al.
(författare)
-
A modified Glenn shunt reduces right ventricular stroke work during left ventricular assist device therapy.
- 2016
-
Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 49:3, s. 795-801
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Right ventricular (RV) failure is a major cause of morbidity and mortality after left ventricular assist device (LVAD) placement and remains hard to predict. We hypothesized that partial surgical exclusion of the RV with a modified Glenn shunt during LVAD treatment would reduce RV stroke work.METHODS: An LVAD was implanted in eight pigs and a modified Glenn shunt was constructed. A conductance pressure-volume catheter was placed in the right ventricle through the apex. Haemodynamic data and pressure-volume loops were obtained at the following time periods: (i) baseline, (ii) open shunt, (iii) LVAD with closed shunt and (iii) LVAD and open shunt.RESULTS: During LVAD therapy, the right atrial (RA) pressure increased from 9 mmHg (9-9) to 15 mmHg (12-15), P = 0.01. RV stroke volume increased from 30 ml (29-40) to 51 ml (42-53), P < 0.01. Also, RV stroke work increased to 708 mmHg ml (654-1193) from 535 mmHg ml (424-717), P = 0.04, compared with baseline. During LVAD therapy in combination with a Glenn shunt, the RA pressure decreased from 15 mmHg (12-15) to 10 mmHg (7-11) when compared with LVAD therapy only, P = 0.01. A decrease in RV stroke work from 708 mmHg ml (654-1193) to 465 mmHg ml (366-711), P = 0.04, was seen when the LVAD was combined with a shunt, not significantly different from the baseline value (535 mmHg ml). The developed pressure in the right ventricle decreased from 29 mmHg (26-32) to 21 mmHg (20-24), P < 0.01. The pressure-volume loops of the RV show a significant reduction of RV stroke work during the use of the shunt with LVAD treatment.CONCLUSIONS: A modified Glenn shunt reduced RV volumes, RV stroke work and RA pressure during LVAD therapy in an experimental model of heart failure in pigs.
|
|
| 9. |
- Schiller, Petter, et al.
(författare)
-
Experimental Venoarterial Extracorporeal Membrane Oxygenation Induces Left Ventricular Dysfunction
- 2016
-
Ingår i: ASAIO journal (1992). - 1058-2916 .- 1538-943X. ; 62:5, s. 518-524
-
Tidskriftsartikel (refereegranskat)abstract
- Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has experienced an increased use in acute cardiac failure. There are some reports on negative effects of VA-ECMO on cardiac function, such as left ventricular (LV) dilatation and cardiac stun, but the support in the literature is scarce. This study investigates the effects of experimental VA-ECMO on LV function in both peripheral and central cannulation. Ten pigs were randomized to VA-ECMO by either peripheral cannulation through the femoral vessels or central cannulation in the right atrium and ascending aorta. Left ventricular performance was measured with pressure-volume catheters during 5 hours of VA-ECMO. The LV enddiastolic and end-systolic volumes increased comparably in both groups during ECMO. Left ventricular ejection fraction, stroke work, and maximum rate of pressure change decreased comparably in both groups as a function of time on ECMO. The site of cannulation had no impact on the LV response to ECMO. In conclusion, VA-ECMO increased LV volumes and reduced LV function, irrespective of cannulation site in this experimental model. Reduced LV ejection fraction and stroke work indicated LV dysfunction during ECMO.
|
|
| 10. |
|
|
