Vascular injury promotes the influx of inflammatory cells and induces apoptosis in vascular smooth muscle cells and endothelial cells. Our studies will examine the mechanisms that control the viability of both inflammatory and vascular cells and assess the consequences of these processes on vascular lesion formation. As in the original grant, studies will predominantly focus on the Fas/Fas ligand regulatory system. This research involves the construction of new animal models and performing mechanistic studies to delineate the signaling mechanisms that control the expression of apoptosis-regulatory molecules. To more fully understand the regulation and role of apoptosis in vessel wall lesion formation we propose the following specific aims: 1) Characterize a new mouse line that lacks functional Fas ligand and apolipoprotein E genes and serves as a model of accelerated atherosclerosis that is associated with autoimmune disease. 2) Characterize a new mouse line that over expresses Fas ligand on the vascular endothelium 3) Produce and characterize new mouse models of atherosclerosis where Fas is disrupted in specific cell types. 4) Perform mechanistic analyses on the signaling and transcriptional regulators that control the sensitivity of vascular endothelial cells to Fas-mediated apoptosis.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Method to Extend Research in Time (MERIT) Award (R37)
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Pathology A Study Section (PTHA)
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Kohanski, Ronald A
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Boston University
Internal Medicine/Medicine
Schools of Medicine
United States
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Nakamura, Kazuto; Fuster, José J; Walsh, Kenneth (2014) Adipokines: a link between obesity and cardiovascular disease. J Cardiol 63:250-9
Naito, Atsuhiko T; Sumida, Tomokazu; Nomura, Seitaro et al. (2012) Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes. Cell 149:1298-313
Papanicolaou, Kyriakos N; Kikuchi, Ryosuke; Ngoh, Gladys A et al. (2012) Mitofusins 1 and 2 are essential for postnatal metabolic remodeling in heart. Circ Res 111:1012-26
Shimano, Masayuki; Ouchi, Noriyuki; Walsh, Kenneth (2012) Cardiokines: recent progress in elucidating the cardiac secretome. Circulation 126:e327-32
Ogura, Yasuhiro; Ouchi, Noriyuki; Ohashi, Koji et al. (2012) Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical models. Circulation 126:1728-38
Konter, Jason M; Parker, Jennifer L; Baez, Elizabeth et al. (2012) Adiponectin attenuates lipopolysaccharide-induced acute lung injury through suppression of endothelial cell activation. J Immunol 188:854-63
Ngoh, Gladys A; Papanicolaou, Kyriakos N; Walsh, Kenneth (2012) Loss of mitofusin 2 promotes endoplasmic reticulum stress. J Biol Chem 287:20321-32
Araki, Satoshi; Izumiya, Yasuhiro; Hanatani, Shinsuke et al. (2012) Akt1-mediated skeletal muscle growth attenuates cardiac dysfunction and remodeling after experimental myocardial infarction. Circ Heart Fail 5:116-25
Ionescu, Lavinia I; Alphonse, Rajesh S; Arizmendi, Narcy et al. (2012) Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma. Am J Respir Cell Mol Biol 46:207-16
Papanicolaou, Kyriakos N; Ngoh, Gladys A; Dabkowski, Erinne R et al. (2012) Cardiomyocyte deletion of mitofusin-1 leads to mitochondrial fragmentation and improves tolerance to ROS-induced mitochondrial dysfunction and cell death. Am J Physiol Heart Circ Physiol 302:H167-79

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