| 1. |
- Murugesan, Vignesh, et al.
(författare)
-
β-Sarcoglycan Deficiency Reduces Atherosclerotic Plaque Development in ApoE-Null Mice
- 2017
-
Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 54, s. 235-245
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Smooth muscle cells are important for atheroscleroticplaque stability. Their proper ability to communicatewith the extracellular matrix is crucial for maintainingthe correct tissue integrity. In this study, we have investigatedthe role of β-sarcoglycan within the matrix-binding dystrophin-glycoproteincomplex in the development of atherosclerosis.Results: Atherosclerotic plaque developmentwas significantly reduced in ApoE-deficient mice lackingβ-sarcoglycan, and their plaques contained an increase indifferentiated smooth muscle cells. ApoE-deficient micelacking β-sarcoglycan showed a reduction in ovarian adiposetissue and adipocyte size, while the total weight of theanimals was not significantly different. Western blot analysisof adipose tissues showed a decreased activation of proteinkinase B, while that of AMP-activated kinase was increasedin mice lacking β-sarcoglycan. Analysis of plasma in β-sarcoglycan-deficientmice revealed reduced levels of leptin,adiponectin, insulin, cholesterol, and triglycerides but in-creased levels of IL-6, IL-17, and TNF-α. Conclusions: Our resultsindicate that the dystrophin-glycoprotein complex andβ-sarcoglycan can affect the atherosclerotic process. Furthermore,the results show the effects of β-sarcoglycan deficiencyon adipose tissue and lipid metabolism, which mayalso have contributed to the atherosclerotic plaque reduction.
|
|
| 2. |
- Quattromani, Miriana Jlenia, et al.
(författare)
-
Changes in resting-state functional connectivity after stroke in a mouse brain lacking extracellular matrix components
- 2018
-
Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 112, s. 91-105
-
Tidskriftsartikel (refereegranskat)abstract
- In the brain, focal ischemia results in a local region of cell death and disruption of both local and remote functional neuronal networks. Tissue reorganization following stroke can be limited by factors such as extracellular matrix (ECM) molecules that prevent neuronal growth and synaptic plasticity. The brain's ECM plays a crucial role in network formation, development, and regeneration of the central nervous system. Further, the ECM is essential for proper white matter tract development and for the formation of structures called perineuronal nets (PNNs). PNNs mainly surround parvalbumin/GABA inhibitory interneurons, of importance for processing sensory information. Previous studies have shown that downregulating PNNs after stroke reduces the neurite-inhibitory environment, reactivates plasticity, and promotes functional recovery. Resting-state functional connectivity (RS-FC) within and across hemispheres has been shown to correlate with behavioral recovery after stroke. However, the relationship between PNNs and RS-FC has not been examined. Here we studied a quadruple knock-out mouse (Q4) that lacks four ECM components: brevican, neurocan, tenascin-C and tenascin-R. We applied functional connectivity optical intrinsic signal (fcOIS) imaging in Q4 mice and wild-type (129S1 mice) before and 14 days after photothrombotic stroke (PT) to understand how the lack of crucial ECM components affects neuronal networks and functional recovery after stroke. Limb-placement ability was evaluated at 2, 7 and 14 days of recovery through the paw-placement test. Q4 mice exhibited significantly impaired homotopic RS-FC compared to wild-type mice, especially in the sensory and parietal regions. Changes in RS-FC were significantly correlated with the number of interhemispheric callosal crossings in those same regions. PT caused unilateral damage to the sensorimotor cortex and deficits of tactile-proprioceptive placing ability in contralesional fore- and hindlimbs, but the two experimental groups did not present significant differences in infarct size. Two weeks after PT, a general down-scaling of regional RS-FC as well as the number of regional functional connections was visible for all cortical regions and most notable in the somatosensory areas of both Q4 and wild-type mice. Q4 mice exhibited higher intrahemispheric RS-FC in contralesional sensory and motor cortices compared to control mice. We propose that the lack of growth inhibiting ECM components in the Q4 mice potentially worsen behavioral outcome in the early phase after stroke, but subsequently facilitates modulation of contralesional RS-FC which is relevant for recovery of sensory motor function. We conclude that Q4 mice represent a valuable model to study how the elimination of ECM genes compromises neuronal function and plasticity mechanisms after stroke.
|
|
| 3. |
- Rattik, Sara, et al.
(författare)
-
IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein E knockout mice.
- 2015
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 242:2, s. 506-514
-
Tidskriftsartikel (refereegranskat)abstract
- IL-22 is a recently discovered cytokine that belongs to the family of IL-10 related cytokines. It is produced by activated T-cells and innate lymphoid cells and has been suggested to be involved in tissue repair. As both inflammation and repair play important roles in atherosclerosis we investigated if IL-22 deficiency influences the disease process in Apoe(-/-) mice.
|
|
| 4. |
- Rauch, Uwe, et al.
(författare)
-
Distinctive peri-luminal presence of agrin in murine and human carotid atherosclerotic plaques
- 2018
-
Ingår i: Histology and Histopathology. - 0213-3911. ; 33:7, s. 717-726
-
Tidskriftsartikel (refereegranskat)abstract
- The clinical consequences of arterial atherosclerotic lesions depend, apart from their size, on their composition of cellular and extracellular components. While an intact endothelium at the interface of atherosclerotic plaques towards the blood can prevent its erosion, underlying smooth muscle cells within the plaque can reduce the risk of plaque ruptures, due to the deposition of stabilizing extracellular matrix. Basement membranes underlay and support the function of endothelial cells, and embed smooth muscle cells in the media, the source of most smooth muscle cells within atherosclerotic plaques. In the present study mouse atherosclerotic plaques were comparatively analyzed for the basement membrane components laminin, type IV collagen, perlecan, and agrin. Distinct agrin immunofluorescence was found in the peri-luminal area in mouse carotid atherosclerotic plaques. Agrin was also clearly present in the media, with a significant increase in regions directly associated with plaque tissue. In addition, ten human endarterectomy specimens were investigated for this heparan sulfate proteoglycan. No statistically significant differences in agrin immunofluorescence were noticed between five specimens from symptomatic and five from asymptomatic patients. In all these plaques agrin was present in a distinctive manner in a narrow zone partially or almost completely surrounding the lumen. Additionally it was also present around the small lumina of the CD31-positive neovessels. The presence of agrin at locations with particular importance for the growth and stability of atherosclerotic plaques renders this molecule strategically positioned to influence plaque development and vulnerability.
|
|
| 5. |
- Shami, Annelie, et al.
(författare)
-
Dystrophin deficiency reduces atherosclerotic plaque development in ApoE-null mice.
- 2015
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy. We have previously shown injury-induced neointima formation of the carotid artery in mice with the mdx mutation (causing dystrophin deficiency) to be increased. To investigate the role of dystrophin in intimal recruitment of smooth muscle cells (SMCs) that maintains plaque stability in atherosclerosis we applied a shear stress-modifying cast around the carotid artery of apolipoprotein E (ApoE)-null mice with and without the mdx mutation. The cast induces formation of atherosclerotic plaques of inflammatory and SMC-rich/fibrous phenotypes in regions of low and oscillatory shear stress, respectively. Unexpectedly, presence of the mdx mutation markedly reduced the development of the inflammatory low shear stress plaques. Further characterization of the low shear stress plaques in ApoE-null mdx mice demonstrated reduced infiltration of CD3(+) T cells, less laminin and a higher SMC content. ApoE-null mdx mice were also found to have a reduced fraction of CD3(+) T cells in the spleen and lower levels of cytokines and monocytes in the circulation. The present study is the first to demonstrate a role for dystrophin in atherosclerosis and unexpectedly shows that this primarily involves immune cells.
|
|
