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An immunohistochemical study of arterial lesions due to pulmonary hypertension in patients with congenital heart defects

Published online by Cambridge University Press:  19 August 2008

Vera Demarchi Aiello ,
Maria de Lourdes Higuchi ,
Edgard Augusto Lopes ,
Antonio Augusto Barbosa Lopes ,
Miguel Barbero-Marcial  and
Munir Ebaid
Vera Demarchi Aiello*
Affiliation:
From the Instituto do Coração do Hospital das Clinicas da FMUSP, São Paulo
Maria de Lourdes Higuchi
Affiliation:
From the Instituto do Coração do Hospital das Clinicas da FMUSP, São Paulo
Edgard Augusto Lopes
Affiliation:
From the Instituto do Coração do Hospital das Clinicas da FMUSP, São Paulo
Antonio Augusto Barbosa Lopes
Affiliation:
From the Instituto do Coração do Hospital das Clinicas da FMUSP, São Paulo
Miguel Barbero-Marcial
Affiliation:
From the Instituto do Coração do Hospital das Clinicas da FMUSP, São Paulo
Munir Ebaid
Affiliation:
From the Instituto do Coração do Hospital das Clinicas da FMUSP, São Paulo
*
Dr. Vera D.Aiello, INCOR HCFMUSP, Servico de Patologia, Avenida Dr. Enéas C. Aguiar, 44, 05403-000 São Paulo SP, Brazil. Tel. (011) 282-7766, Ext. 252; Fax. (011) 282-2354.
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Abstract

In order to understand some of the cellular mechanisms of interaction in secondary pulmonary vaso-occlusive disease, we studied 21 lung biopsies from patients with different types of congenital cardiac defects. Their ages ranged from four to 248 months (mean 71.5 months; median 41 months). Changes in the cytoskeleton and extracellular matrix were assessed in the arterial wall. Immunostaining was applied to formalin-fixed, paraffin- embedded tissue, using antibodies to muscle-specific actin, vimentin and fibronectin in supra-optimal dilution. The staining for muscle-specific actin in the medial layer revealed a heterogenous pattern, with areas exhibiting low or absent labelling, reflecting a process of dedifferentiation of the smooth muscle cells in those segments. Within intimal proliferative lesions, the expression of muscle-specific actin was variable, being weak in some lesions and strong in those showing concentrically arranged intimal smooth muscle cells, suggesting a reversion of the migrated cells to the contractile phenotype. The endothelial cells of arteries from cases presenting severe qualitative lesions exhibited strong expression of vimentin, reflecting their heightened regenerative activity and/or their necessity to maintain their shape. The expression of fibronectin was greater in the predominantly cellular lesions of the intima when compared to the fibrotic lesions, indicating the role of that matrix glycoprotein in cellular migration and in replicative processes.

Keywords

Pulmonary hypertensionimmunohistochemistrysmooth muscle cellfibronectin
Type
World Forum for Pediatric Cardiology Young Investigator Prize
Information
Cardiology in the Young , Volume 4 , Issue 1 , January 1994 , pp. 37 - 43
Copyright
Copyright © Cambridge University Press 1994

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References

Nikkari, ST, Rantala, I, Pystynen, P. Nikkari, T.Characterization of the phenotype of smooth muscle cells in human fetal aorta on the basis of ultrastructure, immunofluorescence, and the composition of cytoskeletal and cytocontractile proteins. Atherosclerosis 1988; 74: 33–40.CrossRefGoogle ScholarPubMed
Osborn, M, Caselitz, J, Puschel, K, Weber, K.Intermediate filament expression in human vascular smooth muscle and in arteriosclerotic plaques. Virchows Arch 1987; 411:449–458.CrossRefGoogle ScholarPubMed
Kocher, O, Skalli, O, Cerutti, D, Gabbiani, F, Gabbiani, G.Cytoskeletal features of rat aortic cells during development. An electron microscopic, immunohistochemical, and biochemical study. Circ Res 1985; 56: 829–838.CrossRefGoogle ScholarPubMed
Gabbiani, G, Schmid, E, Winter, S, Chaponnier, C, Chastonay, C, Vandekerckove, J, Weber, K, Franke, W.Vascular smooth muscle cells differ from other smooth muscle cells: predominance of vimentin filaments and a specific alpha-type actin. Proc Natl Acad Sci 1981; 78: 298–302.CrossRefGoogle Scholar
Gabbiani, G, Kocher, O, Bloom, WS, Vandekerckhove, J, Weber, K.Actin expression in smooth muscle cells of rat aortic intimal thickening, human atheromatous plaque, and cultured rat aortic media. J Clin Invest 1984; 73: 148–152.CrossRefGoogle ScholarPubMed
Allen, K, Haworth, SG.Cytoskeletal features of immature pulmonary vascular smooth muscle cells: the influence of pulmonary hypertension on normal development. J Pathol 1989; 158: 311–317.CrossRefGoogle ScholarPubMed
Stenman, S, von Smitten, K, Vaheri, A.Fibronectin and atherosclerosis. Acta Med Scand 1980; 642(Supplyes): 165–170.CrossRefGoogle ScholarPubMed
Boudreau, N, Rabinovitch, M.Developmentally regulated changes in extracellular matrix in endothelial and smooth muscle cells in the ductus arteriosus may be related to intimal proliferation. Lab Invest 1991; 64: 187–199.Google ScholarPubMed
Rabinovitch, M, Haworth, SG, Castañeda, AR, Nadas, AS, Reid, L.Lung biopsy in congenital heart disease: a morphometric approach to pulmonary vascular disease. Circulation 1978; 58: 1107–1122.CrossRefGoogle ScholarPubMed
Heath, D, Edwards, JE.The Pathology of hypertensive pulmonary vascular disease. Circulation 1958; 18: 533–544.CrossRefGoogle ScholarPubMed
Hsu, SM, Raine, L, Fnager, H.Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures.J Histochem Cytochem 1981; 29: 577–580.CrossRefGoogle ScholarPubMed
Vacca-Galloway, LL.Differential immunostaining for substance P in Huntington's diseased and normal spinal cord: significance of serial (optimal, supra-optimal and end-point) dilutions of primary anti-serum in comparing biological specimens. Histochemistry 1985; 83: 561–569.CrossRefGoogle ScholarPubMed
Kirkpatrick, P, D' ardenne, AJ.Effects of fixation and enzymatic digestion on the immunohistochemical demonstration of laminin and fibronectin in paraffin embedded tissue. J Clin Pathol 1984; 37: 639–644.CrossRefGoogle ScholarPubMed
Schwartz, SM, Campbell, GR, Campbell, JH.Replication of smooth muscle cells in vascular disease. Circ Res 1986; 58: 427–444.CrossRefGoogle ScholarPubMed
Owens, GK, Loeb, A, Gordon, D, Thompson, MM.Expression of smooth muscle-specific alpha-isoactin in cultured vascular smooth muscle cells: Relationship between growth and cytodifferentiation. J Cell Biol 1986; 102: 343–352.CrossRefGoogle ScholarPubMed
Kocher, O, Gabbiani, F, Gabbiani, G, Reidy, MA, Cokai, MS, Peters, H, Huttner, I.Phenotypic features of smooth muscle cells during the evolution of experimental carotid artery intimal thickening. Biochemical and morphologic studies. Lab Invest 1991; 65: 459–470.Google ScholarPubMed
Prosser, IW, Stenmark, KR, Suthar, M, Crouch, EC, Mecham, PR, Parks, WC.Regional heterogeneity of elastin and collagen gene expression in intralobar arteries in response to hypoxic pulmonary hypertension as demonstrated by in situ hybridization.AmJ Pathol 1989; 135: 1073–1088.Google ScholarPubMed
Tsukada, T, McNutt, MA, Ross, R, Gown, AM.HHF35, a muscle actin-specific monoclonal antibody. Reactivity in normal, reactive, and neoplastic human tissues. Am J Pathol 1987; 127: 389–402.Google ScholarPubMed
Smith, P, Heath, D, Yacoub, M, Madden, B, Caslin, A, Gosney, J. The ultrastructure of plexogenic pulmonary arteriopathy. J Pathol 1990; 160: 111–121.CrossRefGoogle ScholarPubMed
Gabbiani, G, Elemer, G, Guelpa, G, Vallotton, MB, Badonnel, MC, Huttner, I.Morphologic and functional changes of the aortic intima during experimental hypertension. Am J Pathol 1979; 96: 399–422.Google ScholarPubMed
Rabinovitch, M, Bothwell, T, Haykawa, BN, Williams, WG, Trusler, PM, Cutz, E.Pulmonary artery endothelial abnormalities in patients with congenital heart defects and pulmonary hypertension. A correlation of light with scanning electron microscopy and transmission electron microscopy. Lab Invest 1986; 55: 632–653.Google ScholarPubMed
Schwartz, SM, Heimark, RL, Majesty, MW.Developmental mechanisms underlying pathology of arteries. Physiol Rev 1990; 70: 1177–1209.CrossRefGoogle ScholarPubMed
Lazarides, E.Intermediate filaments as mechanical integrators of cellular space. Nature 1980; 283: 249–256.CrossRefGoogle ScholarPubMed
Smith, P, Heath, D.Electron microscopy of the plexiform lesion. Thorax 1979; 34: 177–186.CrossRefGoogle ScholarPubMed
Darnel, J, Harvey, L, Baltimore, D.Molecular Cell Biology. 2nd edition. Scientific American Books, Inc., New York, 1990, pp 903–951.Google Scholar
Clark, RAF. Potential roles of fibronectin in cutaneous wound repair. Arch Dermatol 1988; 124: 201–206.CrossRefGoogle ScholarPubMed
D'Ardenne, JA, Burns, J, Sykes, BC, Kirkpatrick, P.Comparative distribution of fibronectin and type III collagen in normal human tissues. J Pathol 1983; 141: 55–69.CrossRefGoogle ScholarPubMed
Botney, MD, Kaiser, LR, Cooper, JD, Mecham, RP, Parghi, D, Roby, J, Parks, WC.Extracellular matrix protein gene expression in atherosclerotic hypertensive pulmonary arteries. Am J Pathol 1992; 140: 357–364.Google ScholarPubMed
Wagenvoort, CA.Lung biopsy findings in secondary pulmonary hypertension. Heart Lung 1986; 15: 429–450.Google ScholarPubMed
Sixma, JJ, De Groot, PG.Von Willebrand factor and the blood vessel wall. Mayo Clin Proc 1991; 66: 629–633.CrossRefGoogle ScholarPubMed