nach oben

Erschienen in:

15.10.2018 | Original Article

Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis

verfasst von: Dr. Dr. Raimund H. M. Preidl, MD, DMD, Patrick Möbius, MD, DMD, Manuel Weber, MD, DMD, Kerstin Amann, MD, Friedrich W. Neukam, MD, DMD, Marco Kesting, MD, DMD, Carol-Immanuel Geppert, MD, Falk Wehrhan, MD, DMD

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Microvascular free flap reconstruction has become a standard technique in head and neck reconstructive surgery. Pre-operative radiotherapy is associated with a higher incidence of free flap malperfusion and the need for operative revision. Irradiated vessels present characteristic histomorphological and structural changes. Alterations in endothelial cells of irradiated arteries remain incompletely investigated especially with regard to long-term changes in endothelial dysfunction supporting an intraluminal pro-thrombotic and pro-inflammatory milieu.

Methods

Endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E‑ and P‑selectin, endothelial NO-synthase (eNOS), thrombomodulin and plasminogen activator inhibitor-1 (PAI-1) in irradiated and non-irradiated arteries was analysed using immunohistochemistry and Remmele scale grading. The average radiation dose was 58.7 ± 7.0 Gy; the time interval between end of radiation and tissue sampling was 106.0 ± 86.8 months.

Results

Endothelial expression of ICAM-1, VCAM-1, E‑ and P‑selectin as well as PAI-1 was significantly increased in previously irradiated arteries compared with non-irradiated controls, whereas thrombomodulin and eNOS expression did not show any differences. However, when comparing non-irradiated free flap arteries with irradiated arteries from the head and neck area in respective individuals, eNOS expression was significantly lower in irradiated vessels whereas ICAM-1, VCAM-1, E‑/p-Selectin and PAI-1 showed significantly higher expression levels.

Conclusion

There is ongoing endothelial dysfunction in terms of increased expression of pro-thrombotic and pro-inflammatory markers in irradiated arteries even years after radiotherapy. Treating this endothelial dysfunction might reduce the complication rates associated with microvascular free flap reconstructions in irradiated patients.

Pohlenz P et al (2012) Microvascular free flaps in head and neck surgery: Complications and outcome of 1000 flaps. Int J Oral Maxillofac Surg 41(6):739–743PubMed

Weitz J et al (2016) Accuracy of mandibular reconstruction by three-dimensional guided vascularised fibular free flap after segmental mandibulectomy. Br J Oral Maxillofac Surg 54(5):506–510PubMed

Preidl RH et al (2015) Perioperative factors that influence the outcome of microsurgical reconstructions in craniomaxillofacial surgery. Br J Oral Maxillofac Surg 53(6):533–537PubMed

Tall J et al (2015) Vascular complications after radiotherapy in head and neck free flap reconstruction: Clinical outcome related to vascular biology. Ann Plast Surg 75(3):309–315PubMed

Schultze-Mosgau S et al (2000) Histomorphometric analysis of irradiated recipient vessels and transplant vessels of free flaps in patients undergoing reconstruction after ablative surgery. Int J Oral Maxillofac Surg 29(2):112–118PubMed

Halle M et al (2010) Sustained inflammation due to nuclear factor-kappa B activation in irradiated human arteries. J Am Coll Cardiol 55(12):1227–1236PubMed

Russell NS et al (2009) Novel insights into pathological changes in muscular arteries of radiotherapy patients. Radiother Oncol 92(3):477–483PubMed

Preidl RH et al (2014) Expression of transforming growth factor beta 1‑related signaling proteins in irradiated vessels. Strahlenther Onkol 191(6):518–524PubMed

Mobius P et al (2017) Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region. Strahlenther Onkol 193(11):951–960PubMed

10.

Halle M, Hall P, Tornvall P (2011) Cardiovascular disease associated with radiotherapy: Activation of nuclear factor kappa-B. J Intern Med 269(5):469–477PubMed

11.

Preidl RH et al (2015) Expression of transforming growth factor beta 1‑related signaling proteins in irradiated vessels. Strahlenther Onkol 191(6):518–524PubMed

12.

Mast ME et al (2016) Less increase of CT-based calcium scores of the coronary arteries : Effect three years after breast-conserving radiotherapy using breath-hold. Strahlenther Onkol 192(10):696–704PubMed

13.

Thalhammer C et al (2015) Carotid artery disease after head and neck radiotherapy. Vasa 44(1):23–30PubMed

14.

Scott AS, Parr LA, Johnstone PA (2009) Risk of cerebrovascular events after neck and supraclavicular radiotherapy: A systematic review. Radiother Oncol 90(2):163–165PubMed

15.

Alberdas JL, Shibahara T, Noma H (2003) Histopathologic damage to vessels in head and neck microsurgery. J Oral Maxillofac Surg 61(2):191–196PubMed

16.

Halle M et al (2010) Endothelial activation with prothrombotic response in irradiated microvascular recipient veins. J Plast Reconstr Aesthet Surg 63(11):1910–1916PubMed

17.

Godo S, Shimokawa H (2017) Endothelial Functions. Arterioscler Thromb Vasc Biol 37(9):e108–e114PubMed

18.

Milliat F et al (2006) Influence of endothelial cells on vascular smooth muscle cells phenotype after irradiation: Implication in radiation-induced vascular damages. Am J Pathol 169(4):1484–1495PubMedPubMedCentral

19.

Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction: A marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 23(2):168–175PubMed

20.

Herrmann J, Lerman A (2008) The endothelium—the cardiovascular health barometer. Herz 33(5):343–353PubMed

21.

Hoving S et al (2012) Irradiation induces different inflammatory and thrombotic responses in carotid arteries of wildtype C57BL/6J and atherosclerosis-prone ApoE(−/−) mice. Radiother Oncol 105(3):365–370PubMed

22.

Sievert W et al (2015) Late proliferating and inflammatory effects on murine microvascular heart and lung endothelial cells after irradiation. Radiother Oncol 117(2):376–381PubMed

23.

Sievert W et al (2018) Improved overall survival of mice by reducing lung side effects after high-precision heart irradiation using a small animal radiation research platform. Int J Radiat Oncol Biol Phys 101(3):671–679PubMed

24.

Daiber A et al (2017) Targeting vascular (endothelial) dysfunction. Br J Pharmacol 174(12):1591–1619PubMed

25.

Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8(3):138–140PubMed

26.

Patties I et al (2015) Late inflammatory and thrombotic changes in irradiated hearts of C57BL/6 wild-type and atherosclerosis-prone ApoE-deficient mice. Strahlenther Onkol 191(2):172–179PubMed

27.

Halle M et al (2009) Timing of radiotherapy in head and neck free flap reconstruction—a study of postoperative complications. J Plast Reconstr Aesthet Surg 62(7):889–895PubMed

28.

Quarmby S, Kumar P, Kumar S (1999) Radiation-induced normal tissue injury: Role of adhesion molecules in leukocyte-endothelial cell interactions. Int J Cancer 82(3):385–395PubMed

29.

Sugihara T et al (1999) Preferential impairment of nitric oxide-mediated endothelium-dependent relaxation in human cervical arteries after irradiation. Circulation 100(6):635–641PubMed

30.

Wang J et al (2002) Deficiency of microvascular thrombomodulin and up-regulation of protease-activated receptor-1 in irradiated rat intestine: Possible link between endothelial dysfunction and chronic radiation fibrosis. Am J Pathol 160(6):2063–2072PubMedPubMedCentral

31.

Loghmani H, Conway EM (2018) Exploring traditional and nontraditional roles for thrombomodulin. Blood 132(2):148–158PubMed

32.

Wang J et al (2007) Significance of endothelial dysfunction in the pathogenesis of early and delayed radiation enteropathy. World J Gastroenterol 13(22):3047–3055PubMedPubMedCentral

33.

Martin FA, Murphy RP, Cummins PM (2013) Thrombomodulin and the vascular endothelium: Insights into functional, regulatory, and therapeutic aspects. Am J Physiol Heart Circ Physiol 304(12):H1585–H1597PubMed

34.

Kusza K, Siemionow M (2011) Is the knowledge on tissue microcirculation important for microsurgeon? Microsurgery 31(7):572–579PubMed

35.

Gutterman DD et al (2016) The human Microcirculation regulation of flow and beyond. Circ Res 118(1):157–172PubMedPubMedCentral

36.

Beckman JA et al (2001) Radiation therapy impairs endothelium-dependent vasodilation in humans. J Am Coll Cardiol 37(3):761–765PubMed

37.

Azimzadeh O et al (2015) Integrative proteomics and targeted transcriptomics analyses in cardiac endothelial cells unravel mechanisms of long-term radiation-induced vascular dysfunction. J Proteome Res 14(2):1203–1219PubMed

38.

Chistiakov DA, Orekhov AN, Bobryshev YV (2017) Effects of shear stress on endothelial cells: Go with the flow. Acta Physiol (oxf) 219(2):382–408

39.

Holler V et al (2009) Pravastatin limits radiation-induced vascular dysfunction in the skin. J Invest Dermatol 129(5):1280–1291PubMed

40.

Kruithof EK (2008) Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins. Thromb Haemost 100(6):969–975PubMed

41.

Owens AP 3rd, Mackman N (2014) The antithrombotic effects of statins. Annu Rev Med 65:433–445PubMed

Titel: Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis
verfasst von: Dr. Dr. Raimund H. M. Preidl, MD, DMD
Patrick Möbius, MD, DMD
Manuel Weber, MD, DMD
Kerstin Amann, MD
Friedrich W. Neukam, MD, DMD
Marco Kesting, MD, DMD
Carol-Immanuel Geppert, MD
Falk Wehrhan, MD, DMD
Publikationsdatum: 15.10.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 1/2019
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-018-1382-3

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis

Abstract

Background

Methods

Results

Conclusion

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Abstract

Background

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2019

Heart-sparing volumetric modulated arc therapy for whole lung irradiation

Feasibility of radiotherapy in nonagenarian patients: a retrospective study

Kombinierte Immuntherapie für Patienten mit Hirnmetastasen eines malignen Melanoms: Deeskalation nur unter kontrollierten Bedingungen und engmaschiger Bildgebung

Assessment of a guideline-based heart substructures delineation in left-sided breast cancer patients undergoing adjuvant radiotherapy

Heart toxicity from breast cancer radiotherapy

Dose variability in different lymph node levels during locoregional breast cancer irradiation: the impact of deep-inspiration breath hold

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie