Search: onr:"swepub:oai:gup.ub.gu.se/271090" >
Hypoxic cardiac fib...
Hypoxic cardiac fibroblasts from failing human hearts decrease cardiomyocyte beating frequency in an ALOX15 dependent manner
-
- Sandstedt, Mikael, 1990 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
-
- Rotter Sopasakis, Victoria, 1972 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
-
- Lundqvist, Annika, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Wallenberglaboratoriet,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine,Wallenberg Laboratory
-
show more...
-
- Vukusic, Kristina, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
-
- Oldfors, Anders, 1951 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
-
- Dellgren, Göran, 1961 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
-
- Sandstedt, Joakim (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
-
- Mattsson Hultén, Lillemor, 1951 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine,Institute of Medicine, Department of Molecular and Clinical Medicine
-
show less...
-
(creator_code:org_t)
- 2018-08-23
- 2018
- English.
-
In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8
- Related links:
-
https://journals.plo...
-
show more...
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- A common denominator for patients with heart failure is the correlation between elevated serum levels of proinflammatory cytokines and adverse clinical outcomes. Furthermore, lipoxygenase-induced inflammation is reportedly involved in the pathology of heart failure. Cardiac fibroblasts, which are abundant in cardiac tissue, are known to be activated by inflammation. We previously showed high expression of the lipoxygenase arachidonate 15 lipoxygenase (ALOX15), which catalyzes the conversion of arachidonic acid to 15-hydroxy eicosatetraenoic acid (15-HETE), in ischemic cardiac tissue. The exact roles of ALOX15 and 15-HETE in the pathogenesis of heart failure are however unknown. Biopsies were collected from all chambers of explanted failing human hearts from heart transplantation patients, as well as from the left ventricles from organ donors not suffering from chronic heart failure. Biopsies from the left ventricles underwent quantitative immunohistochemical analysis for ALOX15/B. Gene expression of ALOX enzymes, as well as 15-HETE levels, were examined in cardiac fibroblasts which had been cultured in either hypoxic or normoxic conditions after isolation from failing hearts. After the addition of fibroblast supernatants to human induced pluripotent stem cell-derived cardiomyocytes, intracellular calcium concentrations were measured to examine the effect of paracrine signaling on cardiomyocyte beating frequency. While ALOX15 and ALOX15B were expressed throughout failing hearts as well as in hearts from organ donors, ALOX15 was expressed at significantly higher levels in donor hearts. Hypoxia resulted in a significant increase in gene and protein expression of ALOX15 and ALOX15B in fibroblasts isolated from the different chambers of failing hearts. Finally, preconditioned medium from hypoxic fibroblasts decreased the beating frequency of human cardiomyocytes derived from induced pluripotent stem cells in an ALOX15-dependent manner. In summary, our results demonstrate that ALOX15/B signaling by hypoxic cardiac fibroblasts may play an important role in ischemic cardiomyopathy, by decreasing cardiomyocyte beating frequency.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- 12/15 lipoxygenase
- 12/15-lipoxygenase
- baicalein
- expression
- 15-lipoxygenase-2
- inflammation
- macrophages
- inhibitors
- pathways
- failure
- Science & Technology - Other Topics
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
-
Plos One
(Search for host publication in LIBRIS)
To the university's database