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Arnt E Fiane

Publications and source records attributed to Arnt E Fiane.

8 recordsLinked to original sources
PubMed2006

Decreased endomyocardial RANKL expression in transplant coronary artery disease.

Transplant-associated coronary artery disease (TxCAD) appears to be initiated by endothelial cell activation and inflammation involving inflammatory cytokines and chemokines. Osteoprotegerin (OPG) and receptor activator of nuclear Factor-kappaB ligand (RANKL) have been implicated in cardiovascular disease progression and we measured the expression of these mediators in serum and myocardial biopsies taken serially during the first year after heart transplantation (HTx), relating them to the development of TxCAD. Serum OPG as well as myocardial gene expression of RANK and OPG, but not RANKL, were highest early after HTx and declined progressively. Importantly, patients who develop TxCAD or experience episodes of acute rejection showed a lower myocardial RANKL expression throughout the first year after transplantation than patients without these complications. Our findings may suggest an unrecognized role RANKL in maintaining myocardial and/or endothelial integrity and suggest that RANKL should be further investigated as a parameter that may predict development of TxCAD.

Adolescent↗
PubMed2006

Human complement-activating immunoglobulin (Ig)G3 antibodies are essential for porcine endothelial cell activation.

BACKGROUND: Complement-activating naturally occurring anti-porcine endothelial cell antibodies (Abs) are responsible for hyperacute rejection in porcine-to-primate transplantation, whereas the role of complement in acute vascular rejection, characterized by type II endothelial cell activation, is less well understood. We previously demonstrated a correlation between porcine type II endothelial cell activation, as detected by E-selectin expression, and human immunoglobulin (Ig)G3 anti-Gal alpha1-3Gal (Gal) Abs, which was not seen for IgG1, IgG2 or IgG4. The present study was undertaken to investigate whether there is a causal relationship between human anti-porcine IgG3 Abs and porcine endothelial cell activation. METHODS: IgG3 was isolated employing a Protein A column to 98.3% purity. Porcine endothelial cells were incubated with isolated human IgG3 or the combination of IgG1, IgG2 and IgG4. E-selectin expression and complement activation were investigated by flow cytometry and Western blotting, respectively. RESULTS: Purified IgG3, in contrast to the other IgG subclasses, induced a substantial increase in E-selectin expression. This activation was accompanied by complement activation as detected by C3 cleavage, and was abolished by heat inactivation or by adding the complement inhibitor FUT-175. Depletion of anti-Gal Abs reduced E-selectin expression by 60%, consistent with the presence of complement-activating anti-porcine non-Gal Abs of the IgG3 subclass. CONCLUSIONS: Collectively, these data strengthen the hypothesis that human anti-porcine endothelial cell Abs of the IgG3 subclass are essential for endothelial cell activation in porcine-to-human species grafts and demonstrate such activation to be partly independent of Gal epitopes.

Animals↗
PubMed2005

Low mannose-binding lectin and increased complement activation correlate to allograft vasculopathy, ischaemia, and rejection after human heart transplantation.

AIMS: Transplant-associated coronary artery disease (TxCAD) is a major cause of post-transplant graft failure. The aim of this study was to investigate a possible role of mannose-binding lectin (MBL) deficiency and complement activation in TxCAD. METHODS AND RESULTS: In a prospective study of heart transplant recipients (n=38) with a follow-up of 5.3+/-1.3 years (range: 0.9-6.6), angiographically verified TxCAD (n=6) was correlated to plasma MBL, complement activation, and endothelial activation (soluble E-selectin). MBL deficiency (<100 ng/mL) was detected in 3/6 patients with TxCAD and in 3/32 with non-TxCAD (Kaplan-Meier, P=0.020). Furthermore, one or more acute rejection episodes were observed in 6/6 of the MBL-deficient patients and in 15/32 of the MBL-sufficient patients (chi(2); P=0.016). Complement activation (C4bc) correlated with soluble E-selectin (r=0.36; P=0.027), both being significantly higher in patients with ischaemia detected in the first biopsy (C4bc: 13.4+/-6.1 AU/mL; E-selectin: 96+/-13 ng/mL) than in those without ischaemia (C4bc: 6.3+/-0.5; E-selectin: 51+/-6; P=0.037 and 0.002). Finally, terminal complement complex correlated closely with mortality (P=0.002). CONCLUSION: Low MBL was related to the development of TxCAD and acute rejection and increased complement activation correlated to histopathologic ischaemia and mortality after heart transplantation.

Adult↗
PubMed2003

Mechanism of complement activation and its role in the inflammatory response after thoracoabdominal aortic aneurysm repair.

BACKGROUND: Complement activation contributes to ischemia-reperfusion injury. Patients undergoing thoracoabdominal aortic aneurysm (TAAA) repair suffer extensive ischemia-reperfusion and considerable systemic inflammation. METHODS AND RESULTS: The degree and mechanism of complement activation and its role in inflammation were investigated in 19 patients undergoing TAAA repair. Patients undergoing open infrarenal aortic surgery (n=5) or endovascular descending aortic aneurysm repair (n=6) served as control subjects. Substantial complement activation was seen in TAAA patients but not in controls. C1rs-C1-inhibitor complexes increased moderately, whereas C4bc, C3bBbP, C3bc, and the terminal SC5b-9 complex (TCC) increased markedly after reperfusion, reaching a maximum 8 hours after reperfusion. Interleukin (IL)-1beta, tumor necrosis factor alpha (TNF-alpha), and IL-8 increased significantly in TAAA patients but not in controls, peaking at 24 hours postoperatively and correlating closely with the degree of complement activation. IL-6 and IL-10 increased to a maximum 8 hours after reperfusion in the TAAA patients, were not correlated with complement activation, and increased moderately in the control subjects. Myeloperoxidase and lactoferrin increased markedly before reperfusion in all groups, whereas sICAM-1, sP-selectin, and sE-selectin were unchanged. No increase was observed in complement activation products, IL-1beta, TNF-alpha, or IL-8 in a mannose-binding lectin (MBL)-deficient TAAA patient, whereas IL-6, IL-10, myeloperoxidase, and lactoferrin increased as in the controls. Two other MBL-deficient TAAA patients receiving plasma attained significant MBL levels and showed complement and cytokine patterns identical to the MBL-sufficient TAAA patients. CONCLUSIONS: The data suggest that complement activation during TAAA repair is MBL mediated, amplified through the alternative pathway, and responsible in part for the inflammatory response.

Aged↗
PubMed2003

Perspectives on complement in xenotransplantation.

The crucial role of complement and naturally occurring anti-Gal antibodies in hyperacute rejection of pig transplants to Old World monkeys, apes and humans is well established. This rejection can be prevented by manipulating either system. Although cells, tissues or organs from pigs made transgenic for human complement regulatory proteins escape hyperacute rejection, there is an increasing evidence of a role for complement also in the subsequent acute vascular or delayed xenograft rejection. Furthermore, complement contributes in a general manner to ischemia-reperfusion injury (IRI), irrespective of the organ source. Early complement-mediated endothelial cell activation, although not sufficient to induce hyperacute rejection, may contribute to reduced long-time graft performance. Control of fluid-phase complement activation by soluble complement inhibitors might be an important adjuvant to transgenic organs from the time of organ harvesting through the first post-transplant period. Pharmacologic manipulation of complement is a field in expansion, though still in its infancy. Although an optimal transgenic and cloned pig may be close to reality, the role of complement in xenotransplantation needs to be fully elucidated and a treatment regimen for fluid-phase inhibition is warranted. The story of complement in xenotransplantation is not completed but under continuous revision.

Animals↗
PubMed2002

[Ethical aspects of xenotransplantation].

The motivation for research on animals as a source of cells, tissues and organs for human transplantation (xenotransplantation) is the scarcity of suitable donors for patients with end-stage organ failure. Use of animals in both experimental and clinical settings raise considerable ethical concerns, especially when non-human primates are used. The pig may represent an acceptable source animal for xenotransplantation and is today regarded as the animal of choice. Xenotransplantation seems defensible from an ethical perspective, but should not be performed in humans until preclinical animal-to-animal xenotransplantations have a predictable rate of success and the risk to society at large is negligible. For the individual patient and his or her next of kin involved, issues of autonomy and proper consent procedures must be given high priority. Safeguards must be established, for the patient and for society at large, in relation to health hazards from infectious organisms, particularly retroviruses. Public monitoring of research on and clinical use of xenotransplantation is mandatory.

Animal Rights↗
PubMed2002

Human serum-induced porcine endothelial cell E-selectin expression is associated with IgG3 and IgM anti-Gal antibodies.

Naturally occurring anti-Galalpha1-3Gal (anti-Gal) antibodies and complement induce hyperacute rejection (HAR) of porcine organs transplanted to primates. If the hyperacute reaction is prevented, an acute vascular rejection (AVR) occurs within hours to few days. Antibodies are important for the development of AVR, whereas the role of complement is still not clarified. AVR is characterized by protein synthesis-dependent endothelial cell (EC) activation. In the present study we investigated the relation between EC activation as measured by E-selectin expression, and the concentrations of anti-Gal antibodies of IgM, IgG and IgG subclasses in sera from 80 healthy blood donors selected on the basis of sex and age. There was a significant correlation between E-selectin expression and the concentration of IgG3 anti-Gal (r=0.39; P=0.019), which was not seen for the other IgG subclasses or for total IgG anti-Gal. A modest, but significant correlation was found between the concentration of IgM anti-Gal and E-selectin expression (r=0.38; P=0.040), but not between IgM and IgG3 anti-Gal. There was a large interindividual variation in anti-Gal antibodies, 50-fold for IgM and 70-fold for IgG. Females had significantly higher concentrations of IgM anti-Gal than males (P=0.0006), which was explained by a substantial increase in IgM anti-Gal concentration in younger women. The concentration of IgG anti-Gal and the degree of E-selectin expression did not differ between sex or age groups. In conclusion, the close correlation between anti-Gal antibodies of the potent complement activating IgG3 subclass and porcine EC activation, may imply that these antibodies play a role in EC activation characteristic of AVR.

Adult↗