title: The roles of mediator complex in cardiovascular diseases.
abstract: Despite recent treatment advances, an increase in cardiovascular diseases (CVD) mortality is expected for the next years. Mediator (MED) complex plays key roles in eukaryotic gene transcription. Currently, while numerous studies have correlated MED alterations with several diseases, like cancer or neurological disorders, fewer studies have investigated MED role in CVD initiation and progression. The first finding of MED involvement in these pathologies was the correlation of missense mutations in MED13L gene with transposition of the great arteries. Nowadays, also MED13 and MED15 have been associated with human congenital heart diseases and others could be added, like MED12 that is involved in early mouse development and heart formation. Interestingly, a missense mutation in MED30 gene causes a progressive cardiomyopathy in homozygous mice suggesting a potential role for this subunit also in human CVDs. Moreover, several subunits like MED1, MED13, MED14, MED15, MED23, MED25 and CDK8 exert important roles in glucose and lipid metabolism. Although these evidences derive from in vitro and animal model studies, they indicate that their deregulation may have a significant role in human CVD-related metabolic disorders. Finally, alternative transcripts of MED12, MED19 and MED30 are differently expressed in circulating endothelial progenitor cells thus suggesting they can play a role in the field of regenerative medicine. Overall, further functional studies exploring MED role in human CVD are warranted. The results could allow identifying novel biomarkers to use in combination with imaging techniques for early diagnosis; otherwise, they could be useful to develop targets for novel therapeutic approaches.
authors.affiliation: Institute of Diagnostic and Nuclear Development (SDN), IRCCS, Via E. Gianturco 113, 80143 Naples, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Schiano
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. Electronic address: amelia.casamassimi@unina2.it.
authors.forename: Amelia
authors.initials: A
authors.lastname: Casamassimi
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Vietri
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Rienzo
authors.affiliation: Institute of Diagnostic and Nuclear Development (SDN), IRCCS, Via E. Gianturco 113, 80143 Naples, Italy; Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy; U.O.C. Immunohematology, Transfusion Medicine and Transplant Immunology [SIMT], Regional Reference Laboratory of Transplant Immunology [LIT], Azienda Universitaria Policlinico (AOU), 1st School of Medicine, Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D056892:Mediator Complex / Q000378:metabolism*; D051379:Mice
chemical_list: D056892:Mediator Complex
keywords: Cardiovascular diseases; Congenital heart diseases; Endothelial progenitor cells; Energy homeostasis; Mediator complex; Pluripotency