title: Maternal HIV type 1 infection suppresses MMP-1 expression in endothelial cells of uninfected newborns: nonviral vertical transmission of HIV type 1-related effects.
abstract: HIV-1 infection is associated with vascular alterations. This is accompanied by an increased risk of cardiovascular diseases and Kaposi's sarcoma, an endothelial cell-derived tumor. We investigated the impact of maternal HIV-1 infection on phenotype and gene expression of endothelial cells in newborns. For this reason endothelial precursor cells and differentiated endothelial cells were isolated from cord blood as well as from umbilical veins and arteries of noninfected infants born to HIV-1-infected (H-group) and noninfected (Ngroup) mothers. No apparent differences in proliferation, capillary formation, and expression of endothelial cell markers were detected in these cells. Interestingly, the expression of matrix metalloproteinase was repressed significantly (X2 analysis, p < 0.002) and consistently at the RNA, the protein, and the secretory levels in the H-group as compared to the N-group. Neither treatment with zidovudine (AZT), mutations in the matrix metalloproteinase-1 (MMP-1) promoter, nor epigenetic changes in the promoter methylation pattern were responsible for the repression of MMP-1 expression in H-group endothelial cells. The reduced MMP-1 expression may contribute to the impaired cardiac function that has been observed in children of HIV-1-infected women. Most interestingly, our findings indicate that HIV-1-related effects can be transferred from mother to child in the absence of HIV-1 transmission.
authors.affiliation: Department of Virus-Induced Vasculopathy, Institute of Molecular Virology, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Jörg
authors.forename: Thomas
authors.initials: T
authors.lastname: Grubert
authors.forename: Thomas
authors.initials: T
authors.lastname: Grimm
authors.forename: Eric
authors.initials: E
authors.lastname: Guenzi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Naschberger
authors.forename: Elenore
authors.initials: E
authors.lastname: Samson
authors.forename: Robert
authors.initials: R
authors.lastname: Oostendorp
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.forename: Michael
authors.initials: M
authors.lastname: Stürzl
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D015153:Blotting, Western; D002469:Cell Separation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D042783:Endothelial Cells / Q000201:enzymology*; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D007120:Immunochemistry; D007231:Infant, Newborn; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D012333:RNA, Messenger; D015215:Zidovudine; D004247:DNA; D020781:Matrix Metalloproteinase 1