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Expression of High ...
Expression of High Mobility Group Protein B1 in Cardiac Tissue of Elderly Patients with Coronary Artery Disease with or without Inflammatory Rheumatic Disease
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Bruton, M (författare)
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Hollan, I (författare)
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Xiao, J (författare)
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- Lindroos, E (författare)
- Karolinska Institutet
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Mikkelsen, K (författare)
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Rynning, SE (författare)
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Saatvedt, K (författare)
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Almdahl, SM (författare)
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- Harris, HE (författare)
- Karolinska Institutet
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- Lundberg, IE (författare)
- Karolinska Institutet
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- Wick, C (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-04-21
- 2017
- Engelska.
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Ingår i: Gerontology. - : S. Karger AG. - 1423-0003 .- 0304-324X. ; 63:4, s. 337-349
- Relaterad länk:
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- <b><i>Background:</i></b> It is known from clinical practice and observational studies that elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a significantly increased risk for cardiovascular diseases such as coronary artery disease (CAD) and heart failure. The molecular mechanism, however, is still not known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly conserved single polypeptide expressed in all mammal eukaryotic cells, has been identified to mediate myocardial dysfunction in vitro once released from the nuclei of cardiomyocytes. <b><i>Objective:</i></b> To investigate whether HMGB1 and its receptors are expressed in cardiac muscles of elderly patients with CAD with or without IRD. <b><i>Methods:</i></b> HMGB1 and its 3 well-known receptors, receptor for advanced glycation end products, Toll-like receptor 2 (TLR2), and TLR4, were examined by immunohistochemistry on myocardial biopsy specimens from 18 elderly patients with CAD (10 with IRD, 8 without IRD). Furthermore, total HMGB1 protein levels were measured by Western blot from the cardiac biopsies in 5 patients with and 5 without IRD. <b><i>Results:</i></b> Pathologic cytosolic HMGB1 in cardiomyocytes was massively recorded in all patients with IRD, but only slightly expressed in 1 patient without IRD. Total HMGB1 levels were also consistently lower in myocardial muscle biopsies of patients with IRD compared to those without IRD. Furthermore, all 3 HMGB1 receptors were expressed in cardiomyocytes of all patients. <b><i>Conclusion:</i></b> The increased cytosolic expression of HMGB1 in cardiomyocytes and the lower total amount of HMGB1 in the cardiac specimens of IRD patients is consistent with a greater release of HMGB1 from the myocardial nuclei in IRD than non-IRD individuals. Thus, the HMGB1 signaling pathways may be more easily activated in elderly CAD patients with concomitant IRD and trigger a detrimental inflammatory process causing severe cardiovascular problems. Therefore, targeting HMGB1 in IRD patients might reduce the risk for cardiovascular events.
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- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Bruton, M
-
Hollan, I
-
Xiao, J
-
Lindroos, E
-
Mikkelsen, K
-
Rynning, SE
-
visa fler...
-
Saatvedt, K
-
Almdahl, SM
-
Harris, HE
-
Lundberg, IE
-
Wick, C
-
visa färre...
- Artiklar i publikationen
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Gerontology
- Av lärosätet
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Karolinska Institutet