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Stimulated in vivo synthesis of plasminogen activator inhibitor-1 in human adipose tissue.
Thromb Haemost 2012; 108(3):485-92TH

Abstract

Plasminogen activator inhibitor type-1 (PAI-1) is one of the most important inhibitors of endogenous fibrinolysis. Adipose tissue is a suggested source of the elevated plasma levels of PAI-1 in obesity. The relation between PAI-1 and inflammation is of particular interest, but current knowledge regarding regulation of PAI-1 in adipose tissue is mainly based on animal studies or ex vivo experiments on human cultured adipocytes. So far, no study has described stimulated gene expression and protein synthesis of PAI-1 in vivo in human adipose tissue. We used open heart surgery as a model of acute systemic inflammation. Twenty-two male patients underwent blood sampling and omental and subcutaneous adipose tissue biopsies for gene expression studies before and after surgery. Expression and localisation of PAI-1 antigen was evaluated by immunohistochemistry. After surgery gene expression of PAI-1 increased 27-fold in omental adipose tissue and three-fold in subcutaneous adipose tissue, but no differences were found in tissue-type plasminogen activator (t-PA) mRNA. PAI-1 antigen was localised within endothelial cells and in the adipose tissue interstitium close to vessels. The upregulated gene expression and protein synthesis in adipose tissue was followed by increased concentrations of PAI-1 antigen in plasma. In conclusion, we present for the first time that an acute systemic inflammation in humans increased gene expression and protein synthesis of PAI-1 in adipose tissue and that this increase was most prominent in omental adipose tissue. PAI-1 synthesis in adipose tissue due to acute systemic inflammation may be a link between inflammation and impaired endogenous fibrinolysis.

Authors+Show Affiliations

Cardiology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden. mattias.ekstrom@karolinska.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22740034

Citation

Ekström, Mattias, et al. "Stimulated in Vivo Synthesis of Plasminogen Activator Inhibitor-1 in Human Adipose Tissue." Thrombosis and Haemostasis, vol. 108, no. 3, 2012, pp. 485-92.
Ekström M, Liska J, Eriksson P, et al. Stimulated in vivo synthesis of plasminogen activator inhibitor-1 in human adipose tissue. Thromb Haemost. 2012;108(3):485-92.
Ekström, M., Liska, J., Eriksson, P., Sverremark-Ekström, E., & Tornvall, P. (2012). Stimulated in vivo synthesis of plasminogen activator inhibitor-1 in human adipose tissue. Thrombosis and Haemostasis, 108(3), pp. 485-92. doi:10.1160/TH11-11-0822.
Ekström M, et al. Stimulated in Vivo Synthesis of Plasminogen Activator Inhibitor-1 in Human Adipose Tissue. Thromb Haemost. 2012;108(3):485-92. PubMed PMID: 22740034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stimulated in vivo synthesis of plasminogen activator inhibitor-1 in human adipose tissue. AU - Ekström,Mattias, AU - Liska,Jan, AU - Eriksson,Per, AU - Sverremark-Ekström,Eva, AU - Tornvall,Per, Y1 - 2012/06/28/ PY - 2011/11/30/received PY - 2012/05/07/accepted PY - 2012/6/29/entrez PY - 2012/6/29/pubmed PY - 2013/2/15/medline SP - 485 EP - 92 JF - Thrombosis and haemostasis JO - Thromb. Haemost. VL - 108 IS - 3 N2 - Plasminogen activator inhibitor type-1 (PAI-1) is one of the most important inhibitors of endogenous fibrinolysis. Adipose tissue is a suggested source of the elevated plasma levels of PAI-1 in obesity. The relation between PAI-1 and inflammation is of particular interest, but current knowledge regarding regulation of PAI-1 in adipose tissue is mainly based on animal studies or ex vivo experiments on human cultured adipocytes. So far, no study has described stimulated gene expression and protein synthesis of PAI-1 in vivo in human adipose tissue. We used open heart surgery as a model of acute systemic inflammation. Twenty-two male patients underwent blood sampling and omental and subcutaneous adipose tissue biopsies for gene expression studies before and after surgery. Expression and localisation of PAI-1 antigen was evaluated by immunohistochemistry. After surgery gene expression of PAI-1 increased 27-fold in omental adipose tissue and three-fold in subcutaneous adipose tissue, but no differences were found in tissue-type plasminogen activator (t-PA) mRNA. PAI-1 antigen was localised within endothelial cells and in the adipose tissue interstitium close to vessels. The upregulated gene expression and protein synthesis in adipose tissue was followed by increased concentrations of PAI-1 antigen in plasma. In conclusion, we present for the first time that an acute systemic inflammation in humans increased gene expression and protein synthesis of PAI-1 in adipose tissue and that this increase was most prominent in omental adipose tissue. PAI-1 synthesis in adipose tissue due to acute systemic inflammation may be a link between inflammation and impaired endogenous fibrinolysis. SN - 2567-689X UR - https://www.unboundmedicine.com/medline/citation/22740034/Stimulated_in_vivo_synthesis_of_plasminogen_activator_inhibitor_1_in_human_adipose_tissue_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1160/TH11-11-0822 DB - PRIME DP - Unbound Medicine ER -