| 1. |
- Nallapalli, Rajesh K, et al.
(författare)
-
Targeting filamin A reduces K-RAS-induced lung adenocarcinomas and endothelial response to tumor growth in mice
- 2012
-
Ingår i: Molecular Cancer. - : BioMed Central. - 1476-4598. ; 11:50
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Many human cancer cells express filamin A (FLNA), an actin-binding structural protein that interacts with a diverse set of cell signaling proteins, but little is known about the biological importance of FLNA in tumor development. FLNA is also expressed in endothelial cells, which may be important for tumor angiogenesis. In this study, we defined the impact of targeting Flna in cancer and endothelial cells on the development of tumors in vivo and on the proliferation of fibroblasts in vitro. less thanbrgreater than less thanbrgreater thanMethods: First, we used a Cre-adenovirus to simultaneously activate the expression of oncogenic K-RAS and inactivate the expression of Flna in the lung and in fibroblasts. Second, we subcutaneously injected mouse fibrosarcoma cells into mice lacking Flna in endothelial cells. less thanbrgreater than less thanbrgreater thanResults: Knockout of Flna significantly reduced K-RAS-induced lung tumor formation and the proliferation of oncogenic K-RAS-expressing fibroblasts, and attenuated the activation of the downstream signaling molecules ERK and AKT. Genetic deletion of endothelial FLNA in mice did not impact cardiovascular development; however, knockout of Flna in endothelial cells reduced subcutaneous fibrosarcoma growth and vascularity within tumors. less thanbrgreater than less thanbrgreater thanConclusions: We conclude that FLNA is important for lung tumor growth and that endothelial Flna impacts local tumor growth. The data shed new light on the biological importance of FLNA and suggest that targeting this protein might be useful in cancer therapeutics.
|
|
| 2. |
- Redfors, Björn, et al.
(författare)
-
Effects of doxorubicin on myocardial expression of apolipoprotein-B.
- 2012
-
Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 46:2
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Doxorubicin (DOX) is an effective antitumor agent against a variety of human malignancies but is associated with deleterious side effects, including myocardial damage and heart failure. Myocardial apoB-containing lipoprotein (apoB) is upregulated post myocardial infarction and has been shown to be cardioprotective in this setting by unloading excessive lipid. The aim of this study was to investigate whether apoB expression is increased also in DOX-induced heart failure and whether apoB overexpression protects the heart in DOX-induced myocardial injury. Design: Cardiac function and energy metabolism was studied in mice and rats 24 hours after intraperitoneally administered DOX. Results: We found that the content of apoB was decreased in rat myocardium 24 hours after DOX injection. In contrast, apoB content was increased in the infarcted myocardium of rats 24 hours post ischemia-reperfusion. Moreover, transgenic mice overexpressing apoB had better cardiac function and lower intracellular lipid accumulation compared to wild type mice 24h post DOX. Conclusions: Our findings indicate that depression of the myocardial apoB system may contribute to DOX-induced cardiac injury and that overexpression of apoB is protective, not only in ischemically damaged myocardium, but also in DOX-induced heart failure.
|
|
| 3. |
- Redfors, Björn, et al.
(författare)
-
Effects of doxorubicin on myocardial expression of apolipoprotein-B.
- 2012
-
Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 46:2, s. 93-98
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract OBJECTIVE: Doxorubicin (DOX) is an effective antitumour agent against a variety of human malignancies but is associated with deleterious side effects, including myocardial damage and heart failure. Myocardial apoB-containing lipoprotein (apoB) is upregulated post myocardial infarction and has been shown to be cardioprotective in this setting by unloading excessive lipid. The aim of this study was to investigate whether apoB expression is increased also in DOX-induced heart failure and whether apoB overexpression protects the heart in DOX-induced myocardial injury. DESIGN: Cardiac function and energy metabolism was studied in mice and rats 24 hours after intraperitoneally administered DOX. RESULTS: We found that the content of apoB was decreased in rat myocardium 24 hours after DOX injection. In contrast, apoB content was increased in the infarcted myocardium of rats 24 hours post ischemia-reperfusion. Moreover, transgenic mice overexpressing apoB had better cardiac function and lower intracellular lipid accumulation compared to wild type mice 24 hours post DOX.
|
|
| 4. |
|
|
| 5. |
- Redfors, Björn, et al.
(författare)
-
Myocardial infarct size and area at risk assessment in mice.
- 2012
-
Ingår i: Experimental and clinical cardiology. - 1205-6626. ; 17:4, s. 268-72
-
Tidskriftsartikel (refereegranskat)abstract
- Mouse models of myocardial ischemia and infarction are important in cardiovascular research. Reliable and reproducible assessment of the area at risk (AAR) and infarct size (IS) in mice is vital for deciphering mechanisms behind these common diseases, and for developing and evaluating treatment strategies. The present review will briefly describe and discuss the most common methods for determining the AAR and IS in mouse models of cardiovascular disease. Several methods exist for ex vivo assessment of IS. Conventional histological stains target the fibrous scar and require several days to pass from the time of infarct induction until the animal is euthanized, whereas triphenyltetrazolium-based techniques stain the viable tissue surrounding the infarct and can be performed on tissue harvested within a few hours after infarction. The AAR is usually stained by injecting a dye into the circulation. This dye subsequently distributes to perfused tissue but leaves the AAR unstained. In vivo assessment enables serial measurements of the IS and/or AAR and is sometimes preferable to ex vivo techniques. Echocardiography is usually the method of choice but magnetic resonance imaging-based techniques are also used. The aim of the present review was to provide basic researchers with an introduction to the various techniques used to assess and quantify the IS and AAR in experimental mouse models of myocardial ischemia-reperfusion and infarction.
|
|
| 6. |
|
|
| 7. |
- Scharin Täng, Margareta, 1962, et al.
(författare)
-
Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling
- 2012
-
Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374. ; 22:6, s. 206-211
-
Tidskriftsartikel (refereegranskat)abstract
- IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI.
|
|
| 8. |
- Scharin Täng, Margareta, 1962, et al.
(författare)
-
Velocity Vector Imaging Fails to Quantify Regional Myocardial Dysfunction in a Mouse Model of Isoprenaline-Induced Cardiotoxicity
- 2012
-
Ingår i: Echocardiography-a Journal of Cardiovascular Ultrasound and Allied Techniques. - : Wiley. - 0742-2822. ; 29:7, s. 818-826
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Regional myocardial deformation patterns are important in a variety of cardiac diseases, including stress-induced cardiomyopathy. Velocity-vector-based imaging is a speckle-tracking echocardiography (STE)-based algorithm that has been shown to allow in-depth cardiac phenotyping in humans. Regional posterior wall myocardial dysfunction occurs during severe isoprenaline stress in mice. We have previously shown that regional posterior wall end-systolic transmural strain decreases after severe isoprenaline toxicity in mice. We hypothesize that STE can detect and further quantify these perturbations. Methods and results: Twenty-three mice underwent echocardiographic examination using the VEVO2100 system. Regional transmural radial strain and strain rate were calculated in both parasternal short-axis and parasternal long-axis cine loops using the VisualSonics VEVO 2100 velocity vector imaging (VVI) STE algorithm. Eight C57BL/6 mice underwent baseline echocardiographic examination using the VisualSonics VEVO 770 system, which can acquire >1,000 frames/s cine loops. In a parasternal short-axis cine loop, the heart was divided into six segments, and regional fractional wall thickening (FWT) was assessed manually. The same protocols were also performed 90 minutes post 400 mg/kg intraperitoneally isoprenaline. Regional myocardial FWT is uniform at baseline but increases significantly in anterolateral segments, whereas it decreases significantly in posterior segments (P < 0.05). A similar pattern is seen using the VVI algorithm although the variance is larger, and differences are smaller and fail to reach significance. Conclusions: VVI is less sensitive in detecting regional perturbations in myocardial function than manual tracing, possibly due to the low frame rate in the cine loops used.
|
|
| 9. |
|
|
