title: Immunomediated and ischemia-independent inflammation of coronary microvessels in unstable angina.
abstract: This study investigated whether the myocardium is involved in the acute inflammatory reaction associated with bursts of unstable angina (UA). We looked for the presence of activated DR+ inflammatory cells and the expression patterns, localization, and immunostaining identification of genes for cytokines (IL-1beta, TNF-alpha, IL-6, and IFN-gamma), MCP-1, and iNOS in the left ventricle biopsies from 2-vessel disease anginal patients, 24 with UA and 12 with stable angina (SA), who underwent coronary bypass surgery. Biopsy specimens from 6 patients with mitral stenosis who underwent valve replacement were examined as control hearts (CHs). Plasma levels of IL-2 soluble receptor (sIL-2R) were measured as a marker of systemic immune reaction. In CHs, DR+ cells were undetectable, and cytokine and iNOS mRNA expression were negligible. UA patients had higher sIL-2R levels than SA patients (P<0.01), and their biopsy specimens showed both numerous DR+ cells identified as lymphocytes, macrophages, endothelial cells, and elevated expression levels of cytokine and iNOS genes (from 2.4- to 6.1-fold vs SA; P<0.01). Cytokine and iNOS genes and proteins were localized in endothelial cells without involvement of myocytes. IL-1beta and MCP-1 mRNAs were nearly undetectable. No significant differences were found in the number of DR+ cells, levels of cytokine, and iNOS genes between potentially ischemic and nonischemic left ventricle areas. In SA specimens, DR+ cells were very rare and only mRNAs for TNF-alpha and iNOS genes were overexpressed versus CHs. These results indicated that an acute immunomediated inflammatory reaction, essentially involving coronary microvessels, is demonstrable in UA patients.
authors.affiliation: Clinica Medica Generale e Cardiologia, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. gg.neriserneri@dfc.unifi.it
authors.forename: Gian Gastone
authors.initials: GG
authors.lastname: Neri Serneri
authors.forename: Maria
authors.initials: M
authors.lastname: Boddi
authors.forename: Pietro Amedeo
authors.initials: PA
authors.lastname: Modesti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cecioni
authors.forename: Mirella
authors.initials: M
authors.lastname: Coppo
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Papa
authors.forename: Thomas
authors.initials: T
authors.lastname: Toscano
authors.forename: Antonio
authors.initials: A
authors.lastname: Marullo
authors.forename: Mario
authors.initials: M
authors.lastname: Chiavarelli
mesh_terms: D000328:Adult; D000789:Angina, Unstable / Q000378:metabolism* / Q000473:pathology; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D018932:Chemokine CCL2 / Q000235:genetics; D003331:Coronary Vessels / Q000737:chemistry* / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000032:analysis*; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D018932:Chemokine CCL2; D016207:Cytokines; D006684:HLA-DR Antigens; D018836:Inflammation Mediators; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C496319:NOS2 protein, human