title: SERCA2a in heart failure: role and therapeutic prospects.
abstract: Ca(2+) is a key molecule controlling several cellular processes, from fertilization to cell death, in all cell types. In excitable and contracting cells, such as cardiac myocytes, Ca(2+) controls muscle contractility. The spatial and temporal segregation of Ca(2+) concentrations are central to maintain its concentration gradients across the cells and the cellular compartments for proper function. SERCA2a is a cornerstone molecule for maintaining a balanced concentration of Ca(2+) during the cardiac cycle, since it controls the transport of Ca(2+) to the sarcoplasmic reticulum (SR) during relaxation. Alterations of the activity of this pump have been widely investigated, emphasizing its central role in the control of Ca(2+) homeostasis and consequently in the pathogenesis of the contractile defect seen with heart failure. This review focuses on the molecular characteristics of the pump, its role during the cardiac cycle and the prospects derived from the manipulation of SERCA2a for heart failure treatment.
authors.affiliation: Cardiovascular Research Centre, Heart Failure Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Gianni
authors.forename: Joachim
authors.initials: J
authors.lastname: Chan
authors.forename: Judith K
authors.initials: JK
authors.lastname: Gwathmey
authors.forename: Federica
authors.initials: F
authors.lastname: del Monte
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000502:physiology* / Q000627:therapeutic use; D015316:Genetic Therapy; D006333:Heart Failure / Q000209:etiology* / Q000628:therapy; D006706:Homeostasis; D006801:Humans; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium