| 21. |
- Bratic, A, et al.
(författare)
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The role of mitochondria in aging
- 2013
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Ingår i: The Journal of clinical investigation. - 1558-8238. ; 123:3, s. 951-957
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Tidskriftsartikel (refereegranskat)
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| 22. |
- Bråkenhielm, E, et al.
(författare)
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Lymphatics in the broken heart
- 2021
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Ingår i: The Journal of clinical investigation. - 1558-8238. ; 131:20
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Tidskriftsartikel (refereegranskat)
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| 23. |
- Cannon, Barbara, et al.
(författare)
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Yes, even human brown fat is on fire!
- 2012
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 122:2, s. 486-489
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- That adult humans possess brown fat is now accepted - but is the brown fat metabolically active? Does human brown fat actually combust fat to release heat? In this issue of the JCI, Ouellet et al. demonstrate that metabolism in brown fat really is increased when adult humans are exposed to cold. This boosts the possibility that calorie combustion in brown fat may be of significance for our metabolism and, correspondingly, that the absence of brown fat may increase our proneness to obesity - provided that brown fat becomes activated not only by cold but also through food-related stimuli.
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| 24. |
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| 25. |
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| 26. |
- Chen, Chiu-Yu, et al.
(författare)
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Blood flow reprograms lymphatic vessels to blood vessels.
- 2012
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 122:6
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Tidskriftsartikel (refereegranskat)abstract
- Human vascular malformations cause disease as a result of changes in blood flow and vascular hemodynamic forces. Although the genetic mutations that underlie the formation of many human vascular malformations are known, the extent to which abnormal blood flow can subsequently influence the vascular genetic program and natural history is not. Loss of the SH2 domain-containing leukocyte protein of 76 kDa (SLP76) resulted in a vascular malformation that directed blood flow through mesenteric lymphatic vessels after birth in mice. Mesenteric vessels in the position of the congenital lymphatic in mature Slp76-null mice lacked lymphatic identity and expressed a marker of blood vessel identity. Genetic lineage tracing demonstrated that this change in vessel identity was the result of lymphatic endothelial cell reprogramming rather than replacement by blood endothelial cells. Exposure of lymphatic vessels to blood in the absence of significant flow did not alter vessel identity in vivo, but lymphatic endothelial cells exposed to similar levels of shear stress ex vivo rapidly lost expression of PROX1, a lymphatic fate-specifying transcription factor. These findings reveal that blood flow can convert lymphatic vessels to blood vessels, demonstrating that hemodynamic forces may reprogram endothelial and vessel identity in cardiovascular diseases associated with abnormal flow.
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| 27. |
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| 28. |
- Chou, Meng-Yun, et al.
(författare)
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Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans.
- 2009
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Ingår i: The Journal of clinical investigation. - 1558-8238. ; 119:5, s. 1335-49
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis.
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| 29. |
- Claesson-Welsh, Lena
(författare)
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How the matrix metalloproteinase MMP14 contributes to the progression of colorectal cancer : Comment
- 2020
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 130:3, s. 1093-1095
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Certain matrix metalloproteinase (MMP) family proteins have been associated with cell proliferation and invasion in aggressive cancers. However, attempts to target the MMPs with the hope of treating tumors have thus far failed. In this issue of the JCI, Ragusa and coworkers identified an intestinal cancer subgroup of slow-growing, chemotherapy-resistant, and very aggressive matrix-rich tumors that mimic a hard-to-treat colorectal cancer subtype in humans. These tumors showed downregulated levels of the transcription factor prospero homeobox protein 1 (PROX1), which relieved repression of the matrix metalloproteinase MMP14. Upregulated MMP14 levels correlated with blood vessel dysfunction and a lack of cytotoxic T cells. Notably, blockade of proangiogenic factors in combination with stimulation of the CD40 pathway in the mouse cancer model boosted cytotoxic T cell infiltration. The study illustrates how combinatorial treatments for aggressive, T cell-deficient cancers can launch an antitumor immune response.
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| 30. |
- Crowley, S. D., et al.
(författare)
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Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis
- 2009
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Ingår i: J Clin Invest. - 1558-8238 .- 1558-8238 .- 0021-9738. ; 119:4, s. 943-53
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Tidskriftsartikel (refereegranskat)abstract
- Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Faslpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT1A-deficient lpr mice, and they showed evidence of exaggerated AT1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.
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