title: Abnormalities in Alternative Splicing of Apoptotic Genes and Cardiovascular Diseases.
abstract: Apoptosis is required for normal heart development in the embryo, but has also been shown to be an important factor in the occurrence of heart disease. Alternative splicing of apoptotic genes is currently emerging as a diagnostic and therapeutic target for heart disease. This review addresses the involvement of abnormalities in alternative splicing of apoptotic genes in cardiac disorders including cardiomyopathy, myocardial ischemia and heart failure. Many pro-apoptotic members of the Bcl-2 family have alternatively spliced isoforms that lack important active domains. These isoforms can play a negative regulatory role by binding to and inhibiting the pro-apoptotic forms. Alternative splicing is observed to be increased in various cardiovascular diseases with the level of alternate transcripts increasing elevated in diseased hearts compared to healthy subjects. In many cases these isoforms appear to be the underlying cause of the disease, while in others they may be induced in response to cardiovascular pathologies. Regardless of this, the detection of alternate splicing events in the heart can serve as useful diagnostic or prognostic tools, while those splicing events that seem to play a causative role in cardiovascular disease make attractive future drug targets.
authors.affiliation: Research, Innovation and Engagements, Mangosuthu University of Technology, Durban 4026, South Africa. dlaminiz@mut.ac.za.
authors.forename: Zodwa
authors.initials: Z
authors.lastname: Dlamini
authors.affiliation: Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Polokwane 0727, South Africa. shonisani.tshidino@ul.ac.za.
authors.forename: Shonisani C
authors.initials: SC
authors.lastname: Tshidino
authors.affiliation: College of Agriculture and Environmental Sciences, Department of Life and Consumer Sciences, Florida Science Campus, University of South Africa, Johannesburg 1709, South Africa. hullr@unisa.ac.za.
authors.forename: Rodney
authors.initials: R
authors.lastname: Hull
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D005786:Gene Expression Regulation; D006801:Humans; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins
keywords: Bcl-2; Bnip3; Nix; PUMA; alternative splicing; apoptosis; cardiomyopathies; therapeutic strategies for targeting heart disease associated abnormal splicing