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Open Access 01-12-2023 | Research

Relative expression of hormone receptors by endothelial and smooth muscle cells in proliferative and non-proliferative areas of congenital arteriovenous malformations

Authors: A. M. Utami, J. B. G. Halfwerk, O. J. de Boer, C. Mackaaij, D. R. Pabittei, C. M. A. M. van der Horst, L. B. Meijer-Jorna, A. C. van der Wal

Published in: European Journal of Medical Research | Issue 1/2023

Abstract

Background

Episodic growth due to microvascular proliferations (MVP) has been reported in congenital arteriovenous malformations (AVM), which are normally quiescent lesions composed of mature malformed vessels. Since AVM also may worsen under conditions of hormonal dysregulation, we hypothesized that hormonal influences may stimulate this process of vasoproliferative growth through potential interactions with hormone receptors (HR).

Methods

13 Cases of AVM tissue with histologically documented vasoproliferative growth were analyzed quantitatively for the presence and tissue localization of estrogen receptor (ER), progesterone receptor (PGR), growth hormone receptor (GHR) and follicle-stimulating hormone receptor (FSHR) in relation to resident cells of interest (endothelial cells (EC), smooth muscle cells (SMC) and mast cells (MC)) by applying multiplex immunohistochemistry (IHC) staining. Expression patterns in lesions with MVP and mature vessels were quantified and compared. Available fresh frozen tissues of 3 AVM samples were used to confirm the presence of HR using Reverse-Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR).

Results

All four HR studied were expressed in all cases within EC and SMC in areas of MVP and mature vessels, but not in normal skin tissue. ER, GHR, and FSHR showed more expression in EC of MVP and in SMC of mature vessels. RT-qPCR confirmed presence of all 4 HR in both areas.

Conclusion

Expression of ER, PGR, GHR, and FSHR in vasoproliferative areas of congenital AVM could explain onset of sudden symptomatic growth, as has observed in a subpopulation of patients. These findings may have implications for eventual anti-hormonal targeted therapy in the lesions involved.

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Gupta A, Kozakewich H. Histopathology of vascular anomalies. Clin Plast Surg. 2011;38:31–44. https://doi.org/10.1016/j.cps.2010.08.007.CrossRefPubMed

Brouillard P, Vikkula M. Genetic causes of vascular malformations. Hum Mol Genet. 2007;16:140–9. https://doi.org/10.1093/hmg/ddm211.CrossRef

Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children. Plast Reconstr Surg. 1982;69:421–2.CrossRef

Meijer-Jorna LB, Van Der Loos CM, De Boer OJ, et al. Microvascular proliferation in congenital vascular malformations of skin and soft tissue. J Clin Pathol. 2007;60:798–803. https://doi.org/10.1136/jcp.2006.038885.CrossRefPubMed

Kulungowski AM, Hassanein AH, Nosé V, et al. Expression of androgen, estrogen, progesterone, and growth hormone receptors in vascular malformations. Plast Reconstr Surg. 2012;129:919–24. https://doi.org/10.1097/PRS.0b013e31824ec3fb.CrossRef

Utami AM, Azahaf S, De Boer OJ, et al. A literature review of microvascular proliferation in arteriovenous malformations of skin and soft tissue. J Clin Transl Res. 2021;7:540–57. https://doi.org/10.18053/jctres.07.202104.011.CrossRefPubMedPubMedCentral

Duyka LJ, Fan CY, Coviello-Malle JM, et al. Progesterone receptors identified in vascular malformations of the head and neck. Otolaryngol—Head Neck Surg. 2009;141:491–5. https://doi.org/10.1016/j.otohns.2009.06.012.CrossRefPubMed

Kohout MP, Hansen M, Pribaz JJ, Mulliken JB. Arteriovenous malformations of the head and neck: natural history and management. Plast Reconstr Surg. 1998;102:643–54.CrossRefPubMed

Low DW. Management of adult facial vascular anomalies. Facial Plast Surg. 2003;19:113–30. https://doi.org/10.1055/s-2003-39131.CrossRefPubMed

10.

Upton J, Coombs CJ, Mulliken JB, et al. Vascular malformations of the upper limb: a review of 270 patients. J Hand Surg Am. 1999;24:1019–35. https://doi.org/10.1053/jhsu.1999.1019.CrossRefPubMed

11.

Persky MS, Yoo HJ, Berenstein A. Management of vascular malformations of the mandible and maxilla. Laryngoscope. 2003;113:1885–92. https://doi.org/10.1097/00005537-200311000-00005.CrossRefPubMed

12.

Liu AS, Mulliken JB, Zurakowski D, et al. Extracranial arteriovenous malformations: natural progression and recurrenceafter treatment. Plast Reconstr Surg. 2010;125:1185–94. https://doi.org/10.1097/PRS.0b013e3181d18070.CrossRefPubMed

13.

Marler JJ, Fishman SJ, Kilroy SM, et al. Increased expression of urinary matrix metalloproteinases parallels the extent and activity of vascular anomalies. Pediatrics. 2005;116:38–45. https://doi.org/10.1542/peds.2004-1518.CrossRefPubMed

14.

Maclellan RA, Vivero MP, Purcell P, et al. Expression of follicle-stimulating hormone receptor in vascular anomalies. Plast Reconstr Surg. 2014;133:344e–51e. https://doi.org/10.1097/01.prs.0000438458.60474.fc.CrossRefPubMed

15.

Hou F, Dai Y, Fan CY, et al. Estrogen is involved in hemangioma regression associated with mast cells. Orphanet J Rare Dis. 2018;13:1–8. https://doi.org/10.1186/s13023-018-0928-x.CrossRef

16.

Ishiwata T, Iino Y, Takei H, et al. Tumor angiogenesis as an independent prognostic indicator in human papillary thyroid carcinoma. Oncol Rep. 1998;5:1343–8. https://doi.org/10.3892/or.5.6.1343.CrossRefPubMed

17.

Jenkins D, Wolever T, Rao AV, et al. The New England journal of medicine from nejm.org on March 29, 2011. for personal use only. no other uses without permission. N Engl J Med. 1993;329:21–6.CrossRefPubMed

18.

Vartanian RK, Weidner N. Correlation of intratumoral endothelial cell proliferation with microvessel density (tumor angiogenesis) and tumor cell proliferation in breast carcinoma. Am J Pathol. 1994;144:1188–94.PubMedPubMedCentral

19.

Maclellan RA, Konczyk DJ, Goss JA, Greene AK. Analysis of follicle-stimulating hormone receptor in infantile hemangioma. Ann Plast Surg. 2018;80:S211–3. https://doi.org/10.1097/SAP.0000000000001438.CrossRefPubMedPubMedCentral

20.

Siraj A, Desestret V, Antoine M, et al. Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases. BMC Cancer. 2013;13:246. https://doi.org/10.1186/1471-2407-13-246.CrossRefPubMedPubMedCentral

21.

Radu A, Pichon C, Camparo P, et al. Expression of follicle-stimulating hormone receptor in tumor blood vessels. J Urol. 2011;186:755. https://doi.org/10.1016/j.juro.2011.04.033.CrossRef

22.

Ventéjou S, Machet MC, Herbreteau D, et al. Hormonal receptors in cutaneous vascular malformations: 51 cases. Virchows Arch. 2019. https://doi.org/10.1007/s00428-019-02546-4.CrossRefPubMed

23.

Meijer-Jorna LB, Van Der Loos CM, Teeling P, et al. Proliferation and maturation of microvessels in arteriovenous malformations—expression patterns of angiogenic and cell cycle-dependent factors. J Cutan Pathol. 2012;39:610–20.CrossRefPubMed

24.

Lu L, Bischoff J, Mulliken JB, et al. Increased endothelial progenitor cells and vasculogenic factors in higher-staged arteriovenous malformations. Plast Reconstr Surg. 2011;128:260–9. https://doi.org/10.1097/PRS.0b013e3182268afd.CrossRef

25.

Ryu JY, Kim YH, Lee JS, et al. Oscillatory shear stress promotes angiogenic effects in arteriovenous malformations endothelial cells. Mol Med. 2021. https://doi.org/10.1186/s10020-021-00291-6.CrossRefPubMedPubMedCentral

26.

Kraby MR, Krüger K, Opdahl S, et al. Microvascular proliferation in luminal A and basal-like breast cancer subtypes. J Clin Pathol. 2015;68:891–7. https://doi.org/10.1136/jclinpath-2015-203037.CrossRefPubMed

27.

Pertiwi KR, de Boer OJ, Mackaaij C, et al. Extracellular traps derived from macrophages, mast cells, eosinophils and neutrophils are generated in a time-dependent manner during atherothrombosis. J Pathol. 2019;247:505–12. https://doi.org/10.1002/path.5212.CrossRefPubMedPubMedCentral

28.

Cordelières FP, Bolte S. Experimenters’ guide to colocalization studies. finding a way through indicators and quantifiers, in practice. Methods Cell Biol. 2014;123:395–408. https://doi.org/10.1016/B978-0-12-420138-5.00021-5.CrossRefPubMed

29.

Dijk F, Veenstra VL, Soer EC, et al. Unsupervised class discovery in pancreatic ductal adenocarcinoma reveals cell-intrinsic mesenchymal features and high concordance between existing classification systems. Sci Rep. 2020;10:1–12. https://doi.org/10.1038/s41598-019-56826-9.CrossRef

30.

Ruijter JM, Ramakers C, Hoogaars WMH, et al. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res. 2009;37:e45. https://doi.org/10.1093/nar/gkp045.CrossRefPubMedPubMedCentral

31.

Ramakers C, Ruijter JM, Deprez RHL, Moorman AFM. Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett. 2003;339:62–6. https://doi.org/10.1016/s0304-3940(02)01423-4.CrossRefPubMed

32.

Maclellan RA, Goss JA, Greene AK. Vascular malformation enlargement during menopause. J Craniofac Surg. 2018;29:1271–2. https://doi.org/10.1097/SCS.0000000000004462.CrossRefPubMed

33.

Dama A, Baggio C, Boscaro C, et al. Estrogen receptor functions and pathways at the vascular immune interface. Int J Mol Sci. 2021. https://doi.org/10.3390/ijms22084254.CrossRefPubMedPubMedCentral

34.

Trenti A, Tedesco S, Boscaro C, et al. Estrogen, angiogenesis, immunity and cell metabolism: solving the puzzle. Int J Mol Sci. 2018. https://doi.org/10.3390/ijms19030859.CrossRefPubMedPubMedCentral

35.

Gordon MS. Vascular endothelial growth factor as a target for antiangiogenic therapy. J Clin Oncol. 2000;18:1000–17.

36.

Leung KC, Johannsson G, Leong GM, Ho KKY. Estrogen regulation of growth hormone action. Endocr Rev. 2004;25:693–721. https://doi.org/10.1210/er.2003-0035.CrossRefPubMed

37.

Losordo DW, Isner JM. Brief reviews. Greece Rome. 1969;16:104–15. https://doi.org/10.1017/s0017383500016429.CrossRef

38.

de Mirecki-Garrido M, Guerra B, Mateos-Díaz C, et al. The influence of estrogens on the biological and therapeutic actions of growth hormone in the liver. Pharmaceuticals. 2012;5:758–78. https://doi.org/10.3390/ph5070758.CrossRefPubMedPubMedCentral

39.

Welsh AW, Lannin DR, Young GS, et al. Cytoplasmic estrogen receptor in breast cancer. Clin Cancer Res. 2012;18:118–26. https://doi.org/10.1158/1078-0432.CCR-11-1236.CrossRefPubMed

40.

Silha JV, Krsek M, Hana V, et al. The effects of growth hormone status on circulating levels of vascular growth factors. Clin Endocrinol. 2005;63:79–86. https://doi.org/10.1111/j.1365-2265.2005.02303.x.CrossRef

41.

Meijer-Jorna LB, Van Der Loos CM, De Boer OJ, et al. Microvascular proliferations in arteriovenous malformations relate to high-flow characteristics, inflammation, and previous therapeutic embolization of the lesion. J Am Acad Dermatol. 2013;68:638–46. https://doi.org/10.1016/j.jaad.2012.10.047.CrossRefPubMed

42.

Chen Y, Zhu W, Bollen AW, et al. Evidence of inflammatory cell involvement in brain arteriovenous malformations. Neurosurgery. 2008;62:1340–9. https://doi.org/10.1227/01.neu.0000333306.64683.b5.CrossRefPubMed

43.

Lim CS, Kiriakidis S, Sandison A, et al. Hypoxia-inducible factor pathway and diseases of the vascular wall. J Vasc Surg. 2013;58:219–30. https://doi.org/10.1016/j.jvs.2013.02.240.CrossRefPubMed

44.

Krock BL, Skuli N, Simon MC. Hypoxia-induced angiogenesis: good and evil. Genes Cancer. 2011;2:1117–33. https://doi.org/10.1177/1947601911423654.CrossRefPubMedPubMedCentral

45.

Takagi Y, Kikuta K, Moriwaki T, et al. Expression of thioredoxin-1 and hypoxia inducible factor-1α in cerebral arteriovenous malformations: Possible role of redox regulatory factor in neoangiogenic property. Surg Neurol Int. 2011;2:61. https://doi.org/10.4103/2152-7806.80356.CrossRefPubMedPubMedCentral

46.

Ng I, Tan WL, Ng PY, Lim J. Hypoxia inducible factor-1α and expression of vascular endothelial growth factor and its receptors in cerebral arteriovenous malformations. J Clin Neurosci. 2005;12:794–9. https://doi.org/10.1016/j.jocn.2005.02.005.CrossRefPubMed

47.

Tan HH, Ge ZZ, Gao YJ, et al. The role of HIF-1, angiopoietin-2, Dll4 and Notch1 in bleeding gastrointestinal vascular malformations and thalidomide-associated actions: a pilot in vivo study. J Dig Dis. 2011;12:349–56. https://doi.org/10.1111/j.1751-2980.2011.00506.x.CrossRefPubMed

48.

Gao P, Zhu Y, Ling F, et al. Nonischemic cerebral venous hypertension promotes a pro-angiogenic stage through HIF-1 downstream genes and leukocyte-derived MMP-9. J Cereb Blood Flow Metab. 2009;29:1482–90. https://doi.org/10.1038/jcbfm.2009.67.CrossRefPubMed

49.

Itinteang T, Tan ST, Jia J, et al. Mast cells in infantile haemangioma possess a primitive myeloid phenotype. J Clin Pathol. 2013;66:597–600. https://doi.org/10.1136/jclinpath-2012-201096.CrossRefPubMed

50.

Zierau O, Zenclussen AC, Jensen F. Role of female sex hormones, estradiol and progesterone, in mast cell behavior. Front Immunol. 2012;3:2010–3. https://doi.org/10.3389/fimmu.2012.00169.CrossRef

51.

Zhao XJ, McKerr G, Dong Z, et al. Expression of oestrogen and progesterone receptors by mast cells alone, but not lymphocytes, macrophages or other immune cells in human upper airways. Thorax. 2001;56:205–11. https://doi.org/10.1136/thorax.56.3.205.CrossRefPubMedPubMedCentral

Title: Relative expression of hormone receptors by endothelial and smooth muscle cells in proliferative and non-proliferative areas of congenital arteriovenous malformations
Authors: A. M. Utami
J. B. G. Halfwerk
O. J. de Boer
C. Mackaaij
D. R. Pabittei
C. M. A. M. van der Horst
L. B. Meijer-Jorna
A. C. van der Wal
Publication date: 01-12-2023
Publisher: BioMed Central
Published in: European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-023-01436-5

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Springer Medicine

Relative expression of hormone receptors by endothelial and smooth muscle cells in proliferative and non-proliferative areas of congenital arteriovenous malformations

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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