title: Aging reduces susceptibility of vascular smooth muscle cells to H₂O₂-induced apoptosis through the down-regulation of Jagged1 expression in endothelial cells.
abstract: In addition to excessive proliferation, reduced apoptosis of vascular smooth muscle cells (VSMCs) plays a key role in aging-exaggerated neointima formation after vascular injury. Our previous studies have shown that impaired expression of Jagged1 in the endothelium may be a key event that leads to enhanced VSMC proliferation in the elderly. Here, we are the first to investigate whether the expression of Jagged1 in endothelial cells (ECs) may regulate apoptosis of VSMCs. We discovered that VSMCs co-cultured with senescent ECs exhibited decreased susceptibility to H₂O₂-induced apoptosis compared with those co-cultured with young ECs. Senescent ECs also displayed lower Jagged1 expression compared to young ECs, which was more evident after H₂O₂ stimulation. Overexpression of Jagged1 in senescent ECs significantly promoted H₂O₂-induced apoptosis in the co-cultured VSMCs, whereas silencing Jagged1 expression in young ECs reduced H2O2-induced apoptosis in the co-cultured VSMCs. Our studies also revealed that Jagged1 expressed in ECs exerted its pro-apoptotic activity by lowering expression of the anti-apoptotic protein Bcl-2. These results demonstrate that aging reduces the susceptibility of co-cultured VSMCs to H₂O₂-induced apoptosis through impaired Jagged1 expression in ECs.
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Dehui
authors.initials: D
authors.lastname: Qian
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Pan
authors.initials: P
authors.lastname: Gao
authors.forename: Chunyan
authors.initials: C
authors.lastname: Kuang
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072099:Serrate-Jagged Proteins; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000072099:Serrate-Jagged Proteins; D006861:Hydrogen Peroxide