Publication Date:
1998-09-11
Description:
Hypertrophic cardiomyopathy (HCM) is an inherited form of heart disease that affects 1 in 500 individuals. Here it is shown that calcineurin, a calcium-regulated phosphatase, plays a critical role in the pathogenesis of HCM. Administration of the calcineurin inhibitors cyclosporin and FK506 prevented disease in mice that were genetically predisposed to develop HCM as a result of aberrant expression of tropomodulin, myosin light chain-2, or fetal beta-tropomyosin in the heart. Cyclosporin had a similar effect in a rat model of pressure-overload hypertrophy. These results suggest that calcineurin inhibitors merit investigation as potential therapeutics for certain forms of human heart disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sussman, M A -- Lim, H W -- Gude, N -- Taigen, T -- Olson, E N -- Robbins, J -- Colbert, M C -- Gualberto, A -- Wieczorek, D F -- Molkentin, J D -- HL58224-01/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1998 Sep 11;281(5383):1690-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9733519" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcineurin/metabolism
;
*Calcineurin Inhibitors
;
Calcium/metabolism
;
*Cardiac Myosins
;
Cardiomegaly/metabolism/pathology/*prevention & control
;
Cardiomyopathy, Dilated/pathology/*prevention & control
;
Cardiomyopathy, Hypertrophic/genetics/metabolism/pathology/*prevention & control
;
Carrier Proteins/genetics
;
Cyclosporine/*pharmacology
;
Female
;
Mice
;
Mice, Transgenic
;
*Microfilament Proteins
;
Models, Cardiovascular
;
Myocardium/*metabolism/pathology
;
Myosin Light Chains/genetics/metabolism
;
Rats
;
Signal Transduction
;
Tacrolimus/*pharmacology
;
Tropomodulin
;
Tropomyosin/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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