Document Detail


Early heart failure in the SMNDelta7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery.
MedLine Citation:
PMID:  20639395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proximal spinal muscular atrophy (SMA) is a debilitating neurological disease marked by isolated lower motor neuron death and subsequent atrophy of skeletal muscle. Historically, SMA pathology was thought to be limited to lower motor neurons and the skeletal muscles they control, yet there are several reports describing the coincidence of cardiovascular abnormalities in SMA patients. As new therapies for SMA emerge, it is necessary to determine whether these non-neuromuscular systems need to be targeted. Therefore, we have characterized left ventricular (LV) function of SMA mice (SMN2+/+; SMNΔ7+/+; Smn-/-) and compared it with that of their unaffected littermates at 7 and 14 days of age. Anatomical and physiological measurements made by electrocardiogram and echocardiography show that affected mouse pups have a dramatic decrease in cardiac function. At 14 days of age, SMA mice have bradycardia and develop a marked dilated cardiomyopathy with a concomitant decrease in contractility. Signs of decreased cardiac function are also apparent as early as 7 days of age in SMA animals. Delivery of a survival motor neuron-1 transgene using a self-complementary adeno-associated virus serotype 9 abolished the symptom of bradycardia and significantly decreased the severity of the heart defect. We conclude that severe SMA animals have compromised cardiac function resulting at least partially from early bradycardia, which is likely attributable to aberrant autonomic signaling. Further cardiographic studies of human SMA patients are needed to clarify the clinical relevance of these findings from this SMA mouse.
Authors:
Adam K Bevan; Kirk R Hutchinson; Kevin D Foust; Lyndsey Braun; Vicki L McGovern; Leah Schmelzer; Jennifer G Ward; Jeffrey C Petruska; Pamela A Lucchesi; Arthur H M Burghes; Brian K Kaspar
Related Documents :
18285565 - The myoblast autologous grafting in ischemic cardiomyopathy (magic) trial: first random...
10024865 - Ventricular constraint in the fetus and newborn.
11090805 - Effect of left ventricular volume on results of coronary artery bypass grafting.
2978875 - Improved left ventricular function after short-term treatment with fructose-1,6-diphosp...
18981625 - Is chronic kidney disease associated with coronary artery stenosis or calcification as ...
9243325 - Chronic therapy with nipradilol, a beta-adrenergic blocker, attenuated left ventricular...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-16
Journal Detail:
Title:  Human molecular genetics     Volume:  19     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-30     Completed Date:  2011-03-01     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  3895-905     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Bradycardia* / genetics,  physiopathology,  therapy
Cardiomyopathy, Dilated / pathology,  physiopathology
Dependovirus / genetics*
Disease Models, Animal
Echocardiography
Electrocardiography
Gene Transfer Techniques*
Genetic Therapy
Heart Failure / pathology,  physiopathology*,  therapy
Mice
Mice, Transgenic
Motor Neurons / metabolism
Muscular Atrophy, Spinal / complications,  physiopathology*
Myocardial Contraction
Nerve Tissue Proteins
SMN Complex Proteins
Survival of Motor Neuron 1 Protein / genetics*
Ventricular Function, Left
Grant Support
ID/Acronym/Agency:
2R01-HL5604-12/HL/NHLBI NIH HHS; R01 NS038650/NS/NINDS NIH HHS; R01-NS038650/NS/NINDS NIH HHS; R21 NS064328/NS/NINDS NIH HHS; R21 NS064328-01/NS/NINDS NIH HHS; R21 NS064328-02/NS/NINDS NIH HHS; R21-NS064328/NS/NINDS NIH HHS; RC2 NS069476/NS/NINDS NIH HHS; RC2 NS069476-02/NS/NINDS NIH HHS; RC2-NS069476/NS/NINDS NIH HHS; UL1 RR025755/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Nerve Tissue Proteins; 0/SMN Complex Proteins; 0/Survival of Motor Neuron 1 Protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Genome-wide association of serum bilirubin levels in Korean population.
Next Document:  Mitochondrial GLUT10 facilitates dehydroascorbic acid import and protects cells against oxidative st...