title: Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles.
abstract: Neurodegenerative diseases are largely defined by protein aggregates in affected tissues. Aggregates contain some shared components as well as proteins thought to be specific for each disease. Aggregation has not previously been reported in the normal, aging heart or the hypertensive heart. Detergent-insoluble protein aggregates were isolated from mouse heart and characterized on 2-dimensional gels. Their levels increased markedly and significantly with aging and after sustained angiotensin II-induced hypertension. Of the aggregate components identified by high-resolution proteomics, half changed in abundance with age (392/787) or with sustained hypertension (459/824), whereas 30% (273/901) changed concordantly in both, each P<0.05. One fifth of these proteins were previously associated with age-progressive neurodegenerative or cardiovascular diseases, or both (eg, ApoE, ApoJ, ApoAIV, clusterin, complement C3, and others involved in stress-response and protein-homeostasis pathways). Because fibrosis is a characteristic of both aged and hypertensive hearts, we posited that aging of fibroblasts may contribute to the aggregates observed in cardiac tissue. Indeed, as cardiac myofibroblasts "senesced" (approached their replicative limit) in vitro, they accrued aggregates with many of the same constituent proteins observed in vivo during natural aging or sustained hypertension. In summary, we have shown for the first time that compact (detergent-insoluble) protein aggregates accumulate during natural aging, chronic hypertension, and in vitro myofibroblast senescence, sharing many common proteins. Thus, aggregates that arise from disparate causes (aging, hypertension, and replicative senescence) may have common underlying mechanisms of accrual.
authors.affiliation: From the Central Arkansas Veterans Healthcare System, Little Rock (S.A., F.M., X.W., R.J.S.R., J.L.M.); Department of Geriatrics (S.A., R.J.S.R.), Division of Cardiology (F.M., X.W., S.V.S.P., J.L.M.), and Department of Biochemistry and Molecular Biology (S.G.M., A.J.T., R.J.S.R.), University of Arkansas for Medical Sciences (UAMS), Little Rock; and Department of Cardiology, University of Rome "Tor Vergata", Rome, Italy (F.M., F.R.). AyyadevaraSrinivas@uams.edu rjsr@uams.edu mehtajl@uams.edu.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ayyadevara
authors.affiliation: From the Central Arkansas Veterans Healthcare System, Little Rock (S.A., F.M., X.W., R.J.S.R., J.L.M.); Department of Geriatrics (S.A., R.J.S.R.), Division of Cardiology (F.M., X.W., S.V.S.P., J.L.M.), and Department of Biochemistry and Molecular Biology (S.G.M., A.J.T., R.J.S.R.), University of Arkansas for Medical Sciences (UAMS), Little Rock; and Department of Cardiology, University of Rome "Tor Vergata", Rome, Italy (F.M., F.R.).
authors.forename: Federico
authors.initials: F
authors.lastname: Mercanti
authors.affiliation: From the Central Arkansas Veterans Healthcare System, Little Rock (S.A., F.M., X.W., R.J.S.R., J.L.M.); Department of Geriatrics (S.A., R.J.S.R.), Division of Cardiology (F.M., X.W., S.V.S.P., J.L.M.), and Department of Biochemistry and Molecular Biology (S.G.M., A.J.T., R.J.S.R.), University of Arkansas for Medical Sciences (UAMS), Little Rock; and Department of Cardiology, University of Rome "Tor Vergata", Rome, Italy (F.M., F.R.).
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: From the Central Arkansas Veterans Healthcare System, Little Rock (S.A., F.M., X.W., R.J.S.R., J.L.M.); Department of Geriatrics (S.A., R.J.S.R.), Division of Cardiology (F.M., X.W., S.V.S.P., J.L.M.), and Department of Biochemistry and Molecular Biology (S.G.M., A.J.T., R.J.S.R.), University of Arkansas for Medical Sciences (UAMS), Little Rock; and Department of Cardiology, University of Rome "Tor Vergata", Rome, Italy (F.M., F.R.).
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Mackintosh
authors.affiliation: From the Central Arkansas Veterans Healthcare System, Little Rock (S.A., F.M., X.W., R.J.S.R., J.L.M.); Department of Geriatrics (S.A., R.J.S.R.), Division of Cardiology (F.M., X.W., S.V.S.P., J.L.M.), and Department of Biochemistry and Molecular Biology (S.G.M., A.J.T., R.J.S.R.), University of Arkansas for Medical Sciences (UAMS), Little Rock; and Department of Cardiology, University of Rome "Tor Vergata", Rome, Italy (F.M., F.R.).
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Tackett
authors.affiliation: From the Central Arkansas Veterans Healthcare System, Little Rock (S.A., F.M., X.W., R.J.S.R., J.L.M.); Department of Geriatrics (S.A., R.J.S.R.), Division of Cardiology (F.M., X.W., S.V.S.P., J.L.M.), and Department of Biochemistry and Molecular Biology (S.G.M., A.J.T., R.J.S.R.), University of Arkansas for Medical Sciences (UAMS), Little Rock; and Department of Cardiology, University of Rome "Tor Vergata", Rome, Italy (F.M., F.R.).
authors.forename: Sastry V S
authors.initials: SV
authors.lastname: Prayaga
authors.affiliation: From the Central Arkansas Veterans Healthcare System, Little Rock (S.A., F.M., X.W., R.J.S.R., J.L.M.); Department of Geriatrics (S.A., R.J.S.R.), Division of Cardiology (F.M., X.W., S.V.S.P., J.L.M.), and Department of Biochemistry and Molecular Biology (S.G.M., A.J.T., R.J.S.R.), University of Arkansas for Medical Sciences (UAMS), Little Rock; and Department of Cardiology, University of Rome "Tor Vergata", Rome, Italy (F.M., F.R.).
authors.forename: Francesco
authors.initials: F
authors.lastname: Romeo
authors.affiliation: From the Central Arkansas Veterans Healthcare System, Little Rock (S.A., F.M., X.W., R.J.S.R., J.L.M.); Department of Geriatrics (S.A., R.J.S.R.), Division of Cardiology (F.M., X.W., S.V.S.P., J.L.M.), and Department of Biochemistry and Molecular Biology (S.G.M., A.J.T., R.J.S.R.), University of Arkansas for Medical Sciences (UAMS), Little Rock; and Department of Cardiology, University of Rome "Tor Vergata", Rome, Italy (F.M., F.R.). AyyadevaraSrinivas@uams.edu rjsr@uams.edu mehtajl@uams.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Shmookler Reis
authors.affiliation: From the Central Arkansas Veterans Healthcare System, Little Rock (S.A., F.M., X.W., R.J.S.R., J.L.M.); Department of Geriatrics (S.A., R.J.S.R.), Division of Cardiology (F.M., X.W., S.V.S.P., J.L.M.), and Department of Biochemistry and Molecular Biology (S.G.M., A.J.T., R.J.S.R.), University of Arkansas for Medical Sciences (UAMS), Little Rock; and Department of Cardiology, University of Rome "Tor Vergata", Rome, Italy (F.M., F.R.). AyyadevaraSrinivas@uams.edu rjsr@uams.edu mehtajl@uams.edu.
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics / Q000503:physiopathology*; D002478:Cells, Cultured; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D058628:Myofibroblasts / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000503:physiopathology; D066329:Protein Aggregates / Q000235:genetics / Q000502:physiology; D066263:Protein Aggregation, Pathological / Q000235:genetics*; D040901:Proteomics / Q000379:methods*; D012016:Reference Values; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D066329:Protein Aggregates
keywords: aging (cardiac); cardiovascular diseases; hypertension; neurodegenerative diseases; protein aggregates