title: Effects of pressure overload on extracellular matrix expression in the heart of the atrial natriuretic peptide-null mouse.
abstract: This study tested the hypothesis that atrial natriuretic peptide has direct antihypertrophic actions on the heart by modulating expression of genes involved in cardiac hypertrophy and extracellular matrix production. Hearts of male, atrial natriuretic peptide-null and control wild-type mice that had been subjected to pressure overload after transverse aortic constriction and control unoperated hearts were weighed and subjected to microarray, Northern blot, and immunohistochemical analyses. Microarray and Northern blot analyses were used to identify genes that are regulated differentially in response to stress in the presence and absence of atrial natriuretic peptide. Immunohistochemical analysis was used to identify and localize expression of the protein products of these genes. Atrial natriuretic peptide-null mice demonstrated cardiac hypertrophy at baseline and an exaggerated hypertrophic response to transverse aortic constriction associated with increased expression of the extracellular matrix molecules periostin, osteopontin, collagen I and III, and thrombospondin, as well as the extracellular matrix regulatory proteins, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3, and the novel growth factor pleiotrophin compared with wild-type controls. These results support the hypothesis that atrial natriuretic peptide protects against pressure overload-induced cardiac hypertrophy and remodeling by negative modulation of genes involved in extracellular matrix deposition.
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Dajun
authors.initials: D
authors.lastname: Wang
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: Ji An
authors.initials: JA
authors.lastname: Feng
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Gilbert
authors.initials: G
authors.lastname: Perry
authors.forename: Lan Bo
authors.initials: LB
authors.lastname: Chen
authors.forename: Meiru
authors.initials: M
authors.lastname: Dai
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Chen
mesh_terms: D000818:Animals; D001011:Aorta; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D001794:Blood Pressure; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003250:Constriction; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D011312:Pressure; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D016326:Extracellular Matrix Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor