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Right arrow Transplantation - heart

Eur J Cardiothorac Surg 2006;29:767-771
© 2006 Elsevier Science NL

First year changes of myocardial lymphatic endothelial markers in heart transplant recipients

Hans J. Geissler a , * , Alexey Dashkevich a , Uwe M. Fischer a , Jochen W.U. Fries b , Ferdinand Kuhn-Régnier a , Klaus Addicks c , Uwe Mehlhorn a , Wilhelm Bloch d

a Department of Cardiothoracic Surgery, University of Cologne, Germany
b Institute of Pathology, University of Cologne, Germany
c Department for Anatomy I, University of Cologne, Germany
d Institute for Molecular and Cellular Sports Medicine, German Sports University Cologne, Germany

Received 4 October 2005; received in revised form 7 December 2005; accepted 12 December 2005.

* Corresponding author. Address: Klinik für Herz- und Thoraxchirurgie, im Klinikum der Universität zu Köln, Joseph-Stelzmann-Str. 9, 50924 Köln, Germany. Tel.: +49 221 478 4128; fax: +49 221 478 4186. (Email: hans.geissler{at}uk-koeln.de).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Objective: The lymphatic system plays an important role in interstitial fluid balance, lipid metabolism, and immune response. The recent introduction of specific lymphatic endothelial cell markers has made the investigation of lymphangiogenesis under various conditions and from small tissue samples feasible. It was the purpose of the study to investigate the changes of myocardial lymphatic endothelial markers during the first 12 months after heart transplantation and to analyze if a correlation between lymphatic markers and rejection can be found. Methods: Right ventricular endomyocardial biopsies taken for routine rejection monitoring from 26 heart transplant recipients were investigated. Selected time points were 0.5, 1, 1.5, 6, and 12 months after human heart transplantation (HTX). Immunohistostaining was performed for VEGFR-3, the receptor for lymphangiogenic vascular endothelial growth factors C and D, for LYVE-1, a novel hyaluronan receptor, restricted to lymhatic vessels, and PROX-1, a homeobox gene product, which plays a key role in lymph vessel development and differentiation. Results: Density of VEGFR-3 positive lymphatics did not change during the first 12 months after transplantation. However, in comparison to the 0.5-month biopsy, density of LYVE-1 and PROX-1 positive lymphatics was significantly decreased at 1 month after transplantation (p < 0.03) and at the subsequent time points (p < 0.01). Patients with only moderate rejection during the first 12 months (ISHLT < IIIa) had a significantly higher density of VEGFR-3 at 0.5 month in comparison to patients with at least one episode of clinically relevant rejection (ISHLT IIIa or worse, p < 0.03). Conclusion: Myocardial lymphatics show a significant change of endothelial phenotype after transplantation, as demonstrated by significant quantitative changes of lymphatic endothelial marker density. Patients with at least one rejection of ISHLT IIIa or higher had a significantly lower density of VEGFR-3 at 0.5 month after transplantation. The results of this study warrant further investigation on the impact of transplantation on the lymphatic endothelium. The cause–effect relation between rejection and lymphatic endothelium remains to be investigated.

Key Words: Lymphatic endothelial cells • Myocardial • Transplantation rejection • Transplantation


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 Appendix A
 References
 
The lymphatic system has important roles in various essential body functions, such as fluid homeostasis, intestinal lipid absorption, and immune cell trafficking [1]. In the past, investigation of the lymphatic system was based mostly on dye injection studies, which allowed only limited insight into changes of the initial lymphatics and lymphangiogenesis. Recently, the discovery of the specific lymphatic endothelial cell markers VEGFR-3, LYVE-1, and PROX-1 has made studies of the lymphatic endothelium and lymphangiogenesis under various disease conditions feasible [2–4]. Using these lymphatic markers, a number of studies have been conducted on the effect of tumor lymphangiogenesis on cancer metastatic spread [5,6]. However, despite the lymphatic's essential function in antigen presentation and immune response, the role of lymphangiogenesis in tissue rejection after transplantation has so far only been studied in corneal transplantation [7]. For corneal transplantation, it has been shown that the inhibition of hemangiogenesis and lymphangiogenesis was associated with prolonged graft survival in a murine model [7]. Although rejection, along with infection, remains to be among the leading causes of death after human heart transplantation (HTX) [8], the changes of the myocardial lymphatic endothelium and the course of myocardial lymphangiogenesis after heart transplantation has not yet been investigated. Therefore, it was the purpose of the study (1) to investigate the changes in density of VEGFR-3, LYVE-1, and PROX-1 positive lymphatics in human myocardium during the first 12 months after HTX and (2) to assess the results for a possible link between lymphatic endothelial marker density and rejection.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 Appendix A
 References
 
All procedures were approved by the University of Cologne Medical Faculty Ethics Committee and followed the Declaration of Helsinki guidelines.

2.1 Patients
Right ventricular endomyocardial biopsies from 26 heart transplant recipients, taken for routine rejection monitoring during the first 12 months after HTX, were investigated. Mean age of recipients (21 males) was 55.8 ± 9 years (range 20–68 years). The indication for HTX was terminal heart failure due to dilative cardiomyopathy in eight patients, ischemic cardiomyopathy in 17 patients, and congenital heart disease in one patient. Heart donors (17 males) were 35.8 ± 12.4 years old (range 17–59 years). The cause of brain death was traumatic in 12 cases, subarachnoidal bleeding in six, intracranial bleeding in three, cerebral edema due to ischemia in two, status asthmaticus in one, CO intoxication in one, and thrombosis of V. basilaris in one. The overall ischemia time was 168.5 ± 40.6 min. During organ harvest, donor hearts were perfused with cold crystalloid cardioplegia (Custodiol®, Dr F. Köhler Chemie GmbH, Alsbach-Hähnlein, Germany). All transplantations were performed with bicaval anastomosis. Postoperative immunosuppression in the first 12 months after transplantation consisted of a combination therapy with cyclosporin A (trough levels 220–280 ng/mL), azathioprine or mycophenolic acid, and methyl prednisolone. Low-grade rejection episodes (ISHLT grade > IB < IIIB) were treated by high dose steroids. In case of recurrent rejection episodes, cyclosporin A was replaced with tacrolimus (trough levels 10–15 ng/mL). None of the investigated patients required rejection treatment with anti-thymocyte or anti-lymphocyte antibodies.

In order to investigate a possible link between histologically verified rejection and lymphatic endothelial marker density, we compared the biopsies from patients with no rejection episode >ISHLT grade II during the first 12 months after HTX (n = 17) to biopsies from patients with at least one rejection of ISHLT grade IIIa or higher (n = 9).

2.2 Myocardial biopsies
Right ventricular endomyocardial biopsies, taken during routine rejection monitoring, were used for analysis. For the study, the following time points were investigated: 0.5, 1, 1.5, 6, and 12 months after HTX. Biopsies were immediately fixed in 4% paraformaldehyde for 4 h and thereafter embedded in paraffin. After cutting of 7 µm slices, tissue was deparaffinied in xylene and rehydrated in alcohol (100%, 96%, 70%, and 0.05 m TBS) before pretreatment in citrate buffer at 60 °C for 12 h.

2.3 Immunohistostaining
The immunohistochemical staining was performed according to the ABC-Method (Avidin–Biotin complex). Negative controls were performed for each charge of antibodies. The following antibodies were used for staining of lymphatic endothelial markers: VEGFR-3, (Santa Cruz Biotechnology®, Santa Cruz, CA, USA), LYVE-1 and PROX-1 (Acris Antibodies®, Hiddenhausen, Germany).

The vessel density was calculated from 10 random fields of vision of each biopsy, analyzing the capillary morphology at 40x. The density of vessels was calculated as number per square millimeter.

On several slices an overlay triple fluorescent stains for VEGFR-3, LYVE-1, and PROX-1 was performed using Cy3- and Cy2-conjugated goat-anti-rabbit-antibodies (Dianova, Hamburg, Germany) and ALEXA-350-goat-anti-rabbit-antibody (MoBiTec, Goettingen, Germany). To prevent cross-reaction on the level of secondary goat-anti-rabbit-antibodies, receptors of primary antibodies were blocked between applications by washing with 5% bovine serum albumin (Sigma, St. Louis, MS, USA).

2.4 Statistics
All data were analyzed using SPSS (Statistical Package for Social Sciences) 12.0 for Windows. Data are expressed as mean ± standard deviation or percentages. Statistical analysis was performed by ANOVA for repeated measures and an unpaired t-test as a post hoc comparison. p-values < 0.05 were considered as significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 Appendix A
 References
 
Light microscopy showed intense staining signals for the lymphatic endothelial markers VEGFR-3, LYVE-1, and PROX-1 from numerous vessel structures in the interstitial space in between cardiomyocytes (Fig. 1 ). The vessels were identified as lymphatics due to their thin-walled, irregular lumen with spiny branchlets, which were in close contact with surrounding cardiomyocytes. The morphology of these vessels was clearly distinct from venous, arterial, or capillary vessels.


Figure 1
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  		Fig. 1. Immunohistostaining for lymphatic endothelial markers in right ventricular endomyocardial biopsies taken for routine rejection monitoring after HTX. (A) LYVE-1 positive lymph vessel with typical morphology; (B) PROX-1 positive lymph vessel; and (C) VEGFR-3 positive lymph vessel.

 
Lymphatic vessel density was analyzed separately for each of the investigated lymphatic endothelial markers. The density of VEGFR-3 positive vessels at 0.5 month after HTX was 57.2 ± 27.1 vessels mm–2 and showed no significant change over time, whereas the density of LYVE-1 (0.5 month: 44.9 ± 19.2 mm–2) and PROX-1 (0.5 month: 43.8 ± 17.1 mm–2) positive vessels decreased significantly during the investigated time period (Fig. 2 ).


Figure 2
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  		Fig. 2. Densities of VEGFR-3, LYVE-1, and PROX-1 positive lymph vessels after HTX. In comparison to the first biopsy at 0.5 month after HTX, subsequent biopsies at 1, 1.5, 6, and 12 months showed no difference in density of VEGFR-3 positive lymph vessels. Density of LYVE-1 and PROX-1 positive lymph vessels, however, decreased significantly over time in comparison to the 0.5 month biopsy. One month versus 0.5 month, p < 0.03 (LVYE-1 and PROX-1); 1.5, 6, and 12 months versus 0.5 month * p < 0.01 (LYVE-1 and PROX-1).

 
Overlay triple fluorescent stains for VEGFR-3, LYVE-1, and PROX-1 showed individual VEGFR-3 positive vessels that were not positive for LYVE-1 and PROX-1 (Fig. 3 ).


Figure 3
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  		Fig. 3. Triple fluorescent stain for VEGFR-3, LYVE-1, and PROX-1. (A) VEGFR-3 coupled with Cy3 (red); (B) LYVE-1 coupled with Cy2 (green); (C) PROX-1 coupled with A. Fl. 350 (blue); (D) overlay of Cy3, Cy2, and A. Fl. 350. Triple fluorescent staining (D, overlay) shows a VEGFR-3 positive lymph vessel, which was not positive for LYVE-1 and PROX-1.

 
Comparison of lymph vessel densities from patients with no rejection episode >ISHLT grade II during the first 12 months after HTX (n = 17) to patients with at least one rejection of ISHLT grade IIIa or higher (n = 9) showed a significantly higher density of VEGFR-3 positive vessels at 0.5 month after HTX in patients with no grade III rejection. The subsequent time points, however, showed no difference for VEGFR-3 vessel density between the two groups. No difference between these groups was seen for vessel densities of PROX-1 and LYVE-1 positive vessels (Fig. 4 ).


Figure 4
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  		Fig. 4. Lymph vessel density of VEGFR-3 positive vessels in patients with no rejection higher than grade II and in patients with at least one episode of ISHLT grade IIIa or higher during the first 12 months after transplantation. Patients who had no episode of rejection higher than ISHLT grade II during the first 12 months after HTX showed a significantly higher density of VEGFR-3 positive lymph vessels than patients with at least one episode of rejection grade IIIa or higher at 0.5 month after HTX. There was no difference in vessel density between the two groups in the subsequent biopsies or for LYVE-1 or PROX-1 positive lymph vessels. * p < 0.03 no ISHLT III versus at least one ISHLT III.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
Appendix A
 References
 
Our data show a significant decrease in the density of the lymphatic endothelial markers LYVE-1 and PROX-1 during the first 12 months after HTX, whereas the density of VEGFR-3 remained unchanged. Overlay triple fluorescent stains for VEGFR-3, LYVE-1, and PROX-1 demonstrated the occurrence of VEGFR-3 positive vessels that were not positive for LYVE-1 and PROX-1. These findings suggest that not the absolute density of myocardial lymphatics was altered, but the phenotype of myocardial lymphatic vessels had changed with less vessels expressing the markers LYVE-1 and PROX-1. These changes may reflect the effect of altered lymphangiogenesis due to the impact of transplantation, immunosuppression, immunologic response, or a combination of these factors. Patients with no rejection episode higher than ISHLT grade II during the first 12 months showed a significantly higher density of VEGFR-3 at the time of the first biopsy (0.5 month after HTX) than patients who experienced at least one grade IIIa or higher rejection during the same time period. The later finding supports the theoretical notion for a pathophysiological link between immunologic response and lymphatic vessel phenotype after HTX.

Myocardial edema and lymphatic dysfunction are a common finding in various cardiac disease states [9,10]. With regard to HTX, it has been shown that myocardial edema precedes cellular infiltration in acute rejection and that acute rejection is associated with increased myocardial water content detected by MR imaging [11,12]. Among the mechanisms by which acute rejection after solid organ transplantation may induce edema, is the disturbance of lymph flow by disruption of lymphatic microvascular endothelial junctions, which has been shown in renal transplantation [13,14]. Lymph drainage from experimentally transplanted lungs, bowel, and kidneys to regional lymph nodes usually occurs after 7–14 days after transplantation, meaning that transplant lymphatics have found connection to regional lymphatics at this time point [13]. In experimental lung transplantation, acute rejection was associated with cessation of lymph drainage from the lung graft to the mediastinum [15].

The recent introduction of the specific lymphatic endothelial markers VEGFR-3, PROX-1, and LYVE-1 permits now the study of lymphatic alterations even from very small tissue samples, such as endomyocardial biopsies. These lymphatic markers can be briefly described as follows: VEGFR-3, also referred to as Flt-4, is the receptor for the lymphangiogenic vascular endothelial growth factors C and D (VEGF-C and VEGF-D) and has recently been studied for its role in metastatic tumor spread [3,5,6]. LYVE-1, a novel hyaluronan receptor, has been shown to be restricted to lymhatic vessels in normal tissue and is responsible for the transport of hyaluronan from extracellular matrix to lymph nodes [2]. PROX-1, a homeobox gene product, plays a key role in the development and differentiation of lymphatic vessels [4]. Although the basic biological activity of VEGFR-3, LYVE-1, and PROX-1 has been characterized as outlined above, their exact function and behavior under various physiologic and disease states is mostly unknown. In the current study, various factors may have affected myocardial lymphatics, such as (1) lymphatic disruption, (2) immunologic response, and (3) immunosuppressive drugs. (1) As a result of the operative procedure, virtually all lymphatic connections of the transplanted heart are initially disrupted. In this situation, myocardial excess interstitial fluid is probably removed by lympho-venous connections, epicardial transudation, and pericardial resorption of lymph that drains blindly from disrupted myocardial lymphatics into the pericardial cavity [13,16]. There is no data how long it takes for myocardial lymphatics after transplantation to connect with regional lymph nodes; however, in other solid organ transplants lymphatic connection is established after 7–14 days [13]. (2) The immunologic response of the host may result in inflammation, edema, and destruction of lymphatic endothelial junctions. After myocardial lymphatics have gained connection to host lymphatics, antigens can be presented to regional lymph nodes by this pathway. (3) The potential effects of rejection on myocardial lymphatics may be prevented, attenuated, or altered by immunosupression. A direct effect of immunosuppressive drugs on lymphatics is not known.

In summary, lymphatic endothelial markers undergo significant quantitative alterations after heart transplantation, suggesting a significant change in lymphatic endothelial phenotype. With regard to rejection, it was found that patients with at least one rejection of ISHLT IIIa or higher had a significantly lower density of VEGFR-3 at 0.5 month after transplantation. A possible cause–effect relation between rejection and the lymphatic endothelium, as well as the question whether the observed lymphatic endothelial changes are reversible over time or not, remains to be investigated. As the lymphatic system plays an integral part in immune cell trafficking, inflammatory response, and myocardial fluid balance, it appears plausible to expect an effect of immunologic response and rejection on the lymphatic endothelium. The results of this study warrant further investigation on the impact of transplantation on the lymphatic endothelium.


   Appendix A
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Appendix A
References
 
Conference discussion

Dr S. Aharinejad (Vienna, Austria): This is a very interesting study that necessitates further studies, as you said. I have two questions. First, how did you quantitate the immunocytochemistry?

Dr Geissler : We counted the number of stained vessels.

Dr Aharinejad : Using what? Using which morphometry software?

Dr Geissler : We have counted an average of 10 fields of vision. For each biopsy, 10 fields of vision were counted, and the average number out of these 10 fields of vision was assigned to that biopsy.

Dr Aharinejad : Was this automatic?

Dr Geissler : No. This was visual, manually. You cannot do this automatically. There is no device for that.

Dr Aharinejad : There is one. There are several. The second question, and this is very interesting, the decrease of the FLT-4 (VEGFR-3) receptors in patients experiencing rejection is significantly in correlation with that event. Do you think this is the cause or the result of rejection?

Dr Geissler : Probably the result.

Dr M. Kamler (Essen, Germany): What immunosuppressive regime did you use, and was it the same in all the patients?

Dr Geissler : Initially we use cyclosporin A, which we do change to tacrolimus in case of recurrent rejection. We use, of course, prednisolone and we use either CellCept or azathioprine.

Dr Kamler : Did you differentiate between these groups because angiopathy might be dependent on your regime.

Dr Geissler : The number of patients is far too small to do that. We looked into this, but with this small number, unfortunately this did not yield any result.

Dr C. Stremmel (Freiburg, Germany): I would like to make a comment. We looked at VEGFR-3 in the tumor field, and there are also a couple of papers out in the transplantation field, and we know that this marker is also expressed in dendritic cells. So we know when this marker is upregulated, then you get a higher immune response. When you block VEGFR-3, it has been shown in a Nature Medicine paper from November last year that you get less rejection of corneal transplants.


   Acknowledgments
 
This study has been supported by the Köln Fortune Foundation of the University of Cologne Medical Faculty.


   Footnotes
 
{star} Presented at the joint 19th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 13th Annual Meeting of the European Society of Thoracic Surgeons, Barcelona, Spain, September 25–28, 2005.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Appendix A
 References
 

  1. Zawieja D. Lymphatic biology and the microcirculation: past, present and future. Microcirculation 2005;12:141-150.[CrossRef][Medline]
  2. Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol 1999;144:789-801.[Abstract/Free Full Text]
  3. Kaipainen A, Korhonen J, Mustonen T, van Hinsbergh VW, Fang GH, Dumont D, Breitman M, Alitalo K. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci USA 1995;92:3566-3570.[Abstract/Free Full Text]
  4. Wigle JT, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn MD, Jackson DG, Oliver G. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. Embo J 2002;21:1505-1513.[CrossRef][Medline]
  5. Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K, Detmar M. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med 2001;7:192-198.[CrossRef][Medline]
  6. Shimizu K, Kubo H, Yamaguchi K, Kawashima K, Ueda Y, Matsuo K, Awane M, Shimahara Y, Takabayashi A, Yamaoka Y, Satoh S. Suppression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancer. Cancer Sci 2004;95:328-333.[CrossRef][Medline]
  7. Cursiefen C, Cao J, Chen L, Liu Y, Maruyama K, Jackson D, Kruse FE, Wiegand SJ, Dana MR, Streilein JW. Inhibition of hemangiogenesis and lymphangiogenesis after normal-risk corneal transplantation by neutralizing VEGF promotes graft survival. Invest Ophthalmol Vis Sci 2004;45:2666-2673.[Abstract/Free Full Text]
  8. Taylor DOEL, Boucek MM, Trulock EP, Deng MC, Keck BM, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-second official adult heart transplant report. J Heart Lung Transplant 2005;24:945-955.[CrossRef][Medline]
  9. Laine GA, Allen SJ. Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function. Circ Res 1991;68:1713-1721.[Abstract/Free Full Text]
  10. Geissler HJ, Allen SJ. Myocardial fluid balance: pathophysiology and clinical implications. Thorac Cardiovasc Surg 1998;46(Suppl. 2):242-245discussion 246–7.[Medline]
  11. Sasaguri S, Sunamori M, Saito K, Suzuki A. Early change of myocardial water during acute cardiac allograft rejection. Jpn Circ J 1986;50:1113-1119.[Medline]
  12. Lund G, Morin RL, Olivari MT, Ring WS. Serial myocardial T2 relaxation time measurements in normal subjects and heart transplant recipients. J Heart Transplant 1988;7:274-279.[Medline]
  13. Malek P, Vrubel J. Lymphatic system and organ transplantation. Lymphology 1968;1:4-22.[Abstract/Free Full Text]
  14. Eliska O, Eliskova M, Mirejovsky P. Lymph vessels of the transplanted kidney. Nephron 1986;44:136-141.[Medline]
  15. Ruggiero R, Fietsam Jr. R, Thomas GA, Muz J, Farris RH, Kowal TA, Myles JL, Stephenson LW, Baciewicz Jr. FA. Detection of canine allograft lung rejection by pulmonary lymphoscintigraphy. J Thorac Cardiovasc Surg 1994;108:253-258.[Abstract/Free Full Text]
  16. Stewart RH, Rohn DA, Allen SJ, Laine GA. Basic determinants of epicardial transudation. Am J Physiol 1997;273:H1408-H1414.[Medline]



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