Zusammenfassung
Hintergrund
Das vaskuläre Remodeling der terminalen Strombahn im rechtsventrikulären Myokard nach Herztransplantation (HTx) ist bislang wenig charakterisiert.
Material und Methoden
In rechtsventrikulärenMyokardbiopsieproben (n=79) von 41 HTx-Patienten (mittleres Alter bei HTx 50 Jahre) und 38 nicht-herztransplantierten Patienten (mittleres Alter 48 Jahre) wurde die terminale Strombahn histologisch (Hämalaun & Eosin) und immunhistochemisch mit α-Aktin (glatte Muskelzellen und Perizyten), CD31 (Glykoprotein auf Endothelzellen, konstitutiv exprimiert) und von-Willebrand-Faktor (=vWF, Expression induzierbar durch Stress/Inflammation) charakterisiert.
Ergebnisse
Alle transplantierten Herzen zeigten mehr α-Aktin-(Mittelwert±SEM 62±6/mm2 vs. 33±3/mm2, p=0,001) und vWF-positive (109±9/mm2 vs. 43±6/mm2, p=0,001) jedoch weniger CD31-positive Blutgefäße (732±31/mm2 vs. 873±47/mm2, p=0,011) als nicht-transplantierte Herzen.
Schlussfolgerungen
Vaskuläres Remodeling der terminalen Strombahn im Sinne einer Umverteilung verschiedener morphologischer Blutgefäßklassen ist bei allen Patienten nach HTx nachweisbar. Weitere serielle Untersuchungen müssen die pathophysiologische Bedeutung dieser Veränderungen klären.
Summary
Background
Little is known about vascular remodeling of right ventricular myocardium after heart transplantation (HTx) as compared to small vessel architecture in non-transplanted hearts.
Material and Methods
In right ventricular myocardial specimens (n=79) taken from 41 HTx patients (mean age 50 years) and 38 non-transplanted patients (mean age 48 years) histologic (hemalaun and eosin) and immunohistochemical characterisation (avidin-streptavidin method) of microvasculature was done with α-actin (clone 1A4, Dako, smooth muscle cells and pericytes), CD31 (clone JC/70A, Dako, glycoprotein on endothelial cells, expressed constitutively) and von Willebrand factor (=vWF, clone F8/86, DAKO, expression inducible in case of stress/inflammation). Additionally, all tissue sections were classified according to the International Society for Heart and Lung Transplantation (ISHLT) grading system for acute cellular rejection. For quantitative histomorphometric assessment, light microscopic analysis of blood vessels and heart muscle cells was done by quantitative histomorphometry of cells and blood vessels (>50% of vessel wall antibody-positive, open lumen, simple count even if more than one cross section of the same blood vessel was present in a single field of view). The size of the field was determined by a calibration scale. With regard to light microscopic magnification, the number of targets per area (i. e. 1/mm2) were calculated.
Results
Positive reactivity for α-actin was found in the medial layer of arterioles but also in capillary-sized microvessels strictly restricted to the blood vessel walls. Positive reactivity of vWF and CD31 was found exclusively in the inner part of blood vessel walls. All transplanted hearts showed more α-actin- (62±6 vs 33±3, p=0.001) and vWF-positive (109±9 vs 43±6, p=0.001) but fewer CD31-positive blood vessels (732±31 vs 873±47, p=0.011) than non-transplanted hearts. Except for CD31 the same findings were present when transplanted and non-transplanted males and females were compared. There were no differences in histomorphometric data with respect to gender match or mismatch in the transplanted patients. Additionally, no differences were found when the histomorphometric results in transplanted males and females were compared and the same applied in nontransplanted male and female patients. α-actin- and vWF-positive blood vessels were correlated (r=0.564, p=0.001), but only in transplanted patients.
Conclusions
Vascular remodeling, i. e. redistribution of different morphologic blood vessel classes, occur in all patients after HTx. Further serial analyses will clarify the impact of these changes.
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References
Bernardo A, Ball C, Nolasco L, Moake JF, Dong JF (2004) Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow. Blood 104:100–106
Billingham ME, Cary NR, Hammond ME, Kemnitz J, Marboe C, McCallister HA, Snovar DC, Winters GL, Zerbe A (1990) A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: heart rejection study group. The International Society for Heart Transplantation. J Heart Transplant 9:587–593
Hiemann NE, Hetzer R, Meyer R (2005) Pathomorphologische Befunde nach Herztransplantation: Eine Monocenterstudie an 15 571 rechtsventrikulären Endomyokardbiopsieproben. Z Herz Thorax Gefäßchirurgie 19:209–217
Hiemann NE, Meyer R, Wellnhofer E, Hetzer R (2005) Small vessel disease after heart transplantation: impact of immunological and non-immunological risk factors. Transplant Int 18:908–914
Hong X, Li FZ, Yin ZY, Yan PH, He YX (2000) The change of vWF in vascular endothelial cells under different stress. Zhongguo Ying Yong Sheng Li Xue Za Zhi 16:310–313
Li LX, Nohara R, Okuda K, Hosokawa R, Hata T, Tanaka M, Matsumori A, Fujita M, Tamaki N, Konishi J, Sasayama S (1996) Comparative study of 201Tl-scintigraphic image and myocardial pathologic findings in patients with dilated cardiomyopathy. Ann Nucl Med 10:307–314
Muller AM, Hermanns MI, Skrzynski C, Nesslinger M, Muller KM, Kirkpatrick CJ (2002) Expression of the endothelial markers PECAM-1, vWf, and CD34 in vivo and in vitro. Exp Mol Pathol 72:221–229
Newman PJ (1994) The role of PECAM-1 in vascular cell biology. Ann NY Acad Sci 714:165–174
Owens GK, Kumar MS, Wamhoff BR (2004) Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 84:767–801
Papetti M, Shujath J, Riley KN, Herman IM (2003) FGF-2 antagonizes the TGF-beta1-mediated induction of pericyte alpha-smooth muscle actin expression: a role for myf-5 and Smad-mediated signaling pathways. Invest Ophthalmol Vis Sci 44:4994–5005
Pereira LM, Vianna GM, Mandarimde-Lacerda CA (1998) Morphology and stereology of the myocardium in hypertensive rats. Correlation with the time of nitric oxide synthesis inhibition. Arq Bras Cardiol 70:397–402
Qin F, Impeduglia T, Schaffer P, Dardik H (2003) Overexpression of von Willebrand factor is an independent risk factor for pathogenesis of intimal hyperplasia: preliminary studies. J Vasc Surg 37:433–439
Rakusan K, Cicutti N, Flanagan MF (1994) Changes in the microvascular network during cardiac growth, development, and aging. Cell Mol Biol Res 40:117–122
Schimmenti LA, Yan HC, Madri JA, Albelda SM (1992) Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration. J Cell Physiol 153:417–428
Schwarz F, Mall G, Zebe H, Schmitzer E, Manthey J, Scheurlen H, Kubler W (1984) Determinants of survival in patients with congestive cardiomyopathy: quantitative morphologic findings and left ventricular hemodynamics. Circulation 70:923–928
Sieczkiewicz GJ, Herman IM (2003) TGF-beta 1 signaling controls retinal pericyte contractile protein expression. Microvasc Res 66:190–196
Sisakyan SA (1977) Investigations of capillary network in the myocardium, skeletal muscles, and other organs by modified Gomori’s method for determination of acid phosphatase activity. Cor Vasa 19:363–369
Verbeek MM, Otte-Holler I, Wesseling P, Ruiter DJ, de Waal RM (1994) Induction of alpha-smooth muscle actin expression in cultured human brain pericytes by transforming growth factor-beta 1. Am J Pathol 144:372–382
Wagner DD, Marder VJ (1983) Biosynthesis of von Willebrand protein by human endothelial cells. Identification of a large precursor polypeptide chain. J Biol Chem 258:2065–2067
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Hiemann, N.E., Hetzer, R., Knosalla, C. et al. Das vaskuläre Remodeling des Myokards in der frühen Phase nach Herztransplantation. Z Herz- Thorax- Gefäßchir 20, 29–35 (2006). https://doi.org/10.1007/s00398-006-0530-8
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DOI: https://doi.org/10.1007/s00398-006-0530-8