Natural anticoagulant pathways in normal and transplanted human hearts
We have studied two natural anticoagulant pathways in normal and in transplanted human hearts. The first is the thrombomodulin pathway. Our immunocytochemical results show thrombomodulin localized to endothelium in heart biopsy specimens before transplantation. This reactivity persists in the absence of cellular rejection, but the infiltration of immune cells is associated with a lack of endothelial thrombomodulin. The second pathway is composed of antithrombin III (ATIII) bound to heparan sulfate proteoglycan (HSPG) molecules on endothelial cells. These ATIII-HSPG complexes bind and inactivate thrombin at the endothelial surface. Our immunocytochemical results show ATIII localized to endothelium in heart biopsy specimens before transplantation. This reactivity is present in the absence of vascular rejection as defined by either angiography or microscopy. The absence of thrombomodulin and ATIII is always associated with fibrin deposition within the microcirculation. Thrombomodulin and ATIII pathways appear to be independent, for cellular rejection often is associated with thrombomodulin-negative ATIII-positive endothelium, and vascular rejection often is associated with thrombomodulin-positive ATIII-negative endothelium. Cytokines from activated macrophages down-regulate endothelial thrombomodulin without generally affecting the ATIII-HSPG pathway. Immunosuppressive therapy depletes cytokine-producing cells that affect thrombomodulin, but there presently is no therapy to protect endothelium in vascular rejection. It is possible that heparin could interact with endothelium and bind ATIII to maintain a state of thromboresistance.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
1992 |
|---|---|
| Erschienen: |
1992 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation - 11(1992), 2 Pt 1 vom: 17. März, Seite 342-7 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Labarrere, C A [VerfasserIn] |
|---|
| Themen: |
9000-94-6 |
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| Anmerkungen: |
Date Completed 05.06.1992 Date Revised 17.11.2004 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM012966649 |
|---|
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| 100 | 1 | |a Labarrere, C A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Natural anticoagulant pathways in normal and transplanted human hearts |
| 264 | 1 | |c 1992 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 05.06.1992 | ||
| 500 | |a Date Revised 17.11.2004 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We have studied two natural anticoagulant pathways in normal and in transplanted human hearts. The first is the thrombomodulin pathway. Our immunocytochemical results show thrombomodulin localized to endothelium in heart biopsy specimens before transplantation. This reactivity persists in the absence of cellular rejection, but the infiltration of immune cells is associated with a lack of endothelial thrombomodulin. The second pathway is composed of antithrombin III (ATIII) bound to heparan sulfate proteoglycan (HSPG) molecules on endothelial cells. These ATIII-HSPG complexes bind and inactivate thrombin at the endothelial surface. Our immunocytochemical results show ATIII localized to endothelium in heart biopsy specimens before transplantation. This reactivity is present in the absence of vascular rejection as defined by either angiography or microscopy. The absence of thrombomodulin and ATIII is always associated with fibrin deposition within the microcirculation. Thrombomodulin and ATIII pathways appear to be independent, for cellular rejection often is associated with thrombomodulin-negative ATIII-positive endothelium, and vascular rejection often is associated with thrombomodulin-positive ATIII-negative endothelium. Cytokines from activated macrophages down-regulate endothelial thrombomodulin without generally affecting the ATIII-HSPG pathway. Immunosuppressive therapy depletes cytokine-producing cells that affect thrombomodulin, but there presently is no therapy to protect endothelium in vascular rejection. It is possible that heparin could interact with endothelium and bind ATIII to maintain a state of thromboresistance | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 650 | 7 | |a Receptors, Thrombin |2 NLM | |
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| 700 | 1 | |a Halbrook, H |e verfasserin |4 aut | |
| 700 | 1 | |a Faulk, W P |e verfasserin |4 aut | |
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