Scientists are reporting the first-ever data to show that the enzyme1（酶） calcineurin（磷酸酶） is critical in controlling normal development and function of heart cells, and that loss of the protein leads to heart problems and death in genetically2 modified mice. Published Feb. 26 in the Journal of Biological Chemistry as the paper of the week, and posted online Feb. 19, the research was led by scientists at Cincinnati Children's Hospital Medical Center and the Howard Hughes Medical Institute.
The study demonstrates that calcineurin in hearts of mice is directly linked to proper cardiac muscle（心肌） contraction3, rhythm（节奏，韵律） and maintenance of heart activity. The near total absence of calcineurin in mice leads to heart arrhythmia（心律失常） , failure and death, according to the research team.
Scientists knew previously4 that calcineurin is important to heart function, but the extent of its role had not been defined prior to the current study. Although the research involved mice, it offers important insights for future studies that could lead to new approaches in diagnosis5 and treatment of heart patients, said Marjorie Maillet, Ph.D., the study's first author.
"We found that when you eliminate calcineurin, a pool of genes6 that regulates calcium7 in the heart went awry8（失败，出错） . This leads to defects（缺点，瑕疵） in the growth and proliferation（增殖，扩散） of heart cells, heart disease, arrhythmia, loss of contractility（收缩性，伸缩力） and heart failure and disease," said Dr. Maillet.
Calcium is also important to cardiac growth and the contraction of heart muscle. Previous studies have linked abnormalities in calcium handling to cardiac disease（心脏疾病） , especially in adults. In mice genetically bred for calcineurin deficiency, the researchers saw that this deficiency causes a dramatic reduction in the expression of genes that coordinately regulate calcium-handling and contraction.
The scientists also report a newly identified "feed-forward" mechanism9, in which the direct activation10 of calcineurin by calcium（钙） augments11（增加，增大） the expression of genes that regulate calcium-handling proteins in the heart.
Dr. Maillet works in the laboratory of the study's senior investigator12, Jeffery Molkentin, Ph.D., a researcher in the division of Molecular13 Cardiovascular（心血管的） Biology at Cincinnati Children's and a Howard Hughes Medical Institute Investigator. Dr. Molkentin's laboratory and division are also part of the Cincinnati Children's Heart Institute.
Also collaborating14 on the study were researchers from the University Paris-Sud, Châtenay-Malabry, France and the department of Molecular and Cellular15 Physiology16 at the University of Cincinnati College of Medicine.
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