title: Hypoxia-inducible factor-1α, vascular endothelial growth factor, inducible nitric oxide synthase, and endothelin-1 expression correlates with angiogenesis in congenital heart disease.
abstract: In Taiwan, the average prevalence of congenital heart disease (CHD) is 13.08/1000 live births. Most children with CHD die before the age of 5 years; therefore, identifying treatment methods to extend the life of CHD patients is an important issue in clinical practice. The objective of this study is to evaluate the roles of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), endothelin-1 (ET-1), and CD34 in CHD autopsy cases in comparison with autopsy cases without CHD. The study included 19 autopsy cases, which were divided into the following four groups: acyanotic CHD (n = 11), cyanotic CHD (n = 3), CHD associated with chromosomal abnormalities (n = 3), and complex CHD (n = 2). Heart specimens obtained from 10 autopsy cases without CHD were included as controls. Our results indicated that high percentages of HIF-1α (100%), VEGF (89.5%), iNOS (78.9%), and ET-1 (84.2%) expressions were observed in CHD autopsy cases and this was found to be significant. HIF-1α induced by hypoxia could play a potential role in relating downstream gene expressions in CHD patients. Upregulation of VEGF by HIF-1α could play an important role in triggering angiogenesis to protect myocardial cell survival in a hypoxic microenvironment. Therefore, HIF-1α could be a significant prognosis marker in CHD and be a prospective candidate in the development of target therapy in cardiovascular diseases.
authors.affiliation: Division of Forensic Pathology, Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Anatomic Pathology, Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yin
authors.affiliation: Division of Anatomic Pathology, Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chi-Wen
authors.initials: CW
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pediatrics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Zen-Kong
authors.initials: ZK
authors.lastname: Dai
authors.affiliation: Department of Forensic Pathology, Institute of Forensic Medicine, Ministry of Justice, Taipei, Taiwan.
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Shaw
authors.affiliation: Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Anatomic Pathology, Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.affiliation: Division of Anatomic Pathology, Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: lazzz_wu@yahoo.com.tw.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Wu
mesh_terms: D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006330:Heart Defects, Congenital / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D055806:Microvessels / Q000473:pathology; D018919:Neovascularization, Physiologic; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D052247:Nitric Oxide Synthase Type II
keywords: Endothelin-1; Hypoxia-inducible factor-1α; Inducible nitric oxide synthase; Vascular endothelial growth factor