title: A diet supplemented with ALA-rich flaxseed prevents cardiomyocyte apoptosis by regulating caveolin-3 expression.
abstract: OBJECTIVE
  n-3 polyunsaturated fatty acids (PUFAs) induce beneficial effects on the heart, but the mechanisms through which these effects are operated are not completely clarified yet. Among others, cardiac diseases are often associated with increased levels of cytokines, such as tumour necrosis factor-α (TNF), that cause degeneration and death of cardiomyocytes. The present study has been carried out to investigate (i) the potential anti-apoptotic effects induced by the n-3 polyunsaturated α-linolenic acid (ALA) in experimental models of cardiac diseases characterized by high levels of TNF, and (ii) the potential role of caveolin-3 (Cav-3) in the mechanisms involved in this process.
  
  
  RESULTS
  An ALA-rich flaxseed diet, administered from weaning to hereditary cardiomyopathic hamsters, prevented the onset of myocardial apoptosis associated with high plasma and tissue levels of TNF preserving caveolin-3 expression. To confirm these findings, isolated neonatal mouse cardiomyocytes were exposed to TNF to induce apoptosis. ALA pre-treatment greatly enhanced Cav-3 expression hampering the internalization of the caveolar TNF receptor and, thus, determining the abortion of the apoptotic vs. survival cascade.
  
  
  CONCLUSIONS
  This study unveiled the Cav-3 pivotal role in defending cardiomyocytes against the TNF pro-apoptotic action and the ALA capacity to regulate this mechanism preventing cardiac degenerative diseases.
authors.affiliation: Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Scienze Cliniche e Medicina Traslazionale, Università di Roma Tor Vergata, Via Montpellier, 1, Roma 00133, Italy.
authors.forename: Felicia
authors.initials: F
authors.lastname: Carotenuto
authors.forename: Marilena
authors.initials: M
authors.lastname: Minieri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monego
authors.forename: Roberta
authors.initials: R
authors.lastname: Fiaccavento
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bertoni
authors.forename: Fabiola
authors.initials: F
authors.lastname: Sinigaglia
authors.forename: Alba
authors.initials: A
authors.lastname: Vecchini
authors.forename: Luciana
authors.initials: L
authors.lastname: Carosella
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Nardo
mesh_terms: D000367:Age Factors; D000821:Animal Feed; D000818:Animals; D017209:Apoptosis; D009202:Cardiomyopathies / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D004195:Disease Models, Animal; D019597:Flax / Q000378:metabolism*; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D012639:Seeds / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000378:metabolism*
chemical_list: C495548:Cav3 protein, mouse; D051244:Caveolin 3; D014409:Tumor Necrosis Factor-alpha; D017962:alpha-Linolenic Acid
keywords: Apoptosis; Cardiomyocytes; Caveolin-3; Tumour necrosis factor-α; α-Linolenic acid