Document Detail

The Na+/Ca2+ exchanger-1 mediates left ventricular dysfunction in mice with chronic intermittent hypoxia.
MedLine Citation:
PMID:  20947716     Owner:  NLM     Status:  MEDLINE    
Chronic intermittent hypoxia (CIH) and cardiovascular dysfunction occur in patients with obstructive sleep apnea. We hypothesized that the Na(+)/Ca(2+) exchanger-1 (NCX1) mediates, at least partially, left ventricular (LV) dysfunction in CIH. Four groups of mice (N = 15-17 per group), either cardiac-specific NCX1 knockouts (KO) or wild types (WT), were exposed to either CIH or normoxia [i.e., handled controls (HC)] 10 h/day for 8 wk. As expected, myocardial expression of NCX1 was greater in WT than in KO animals, both in HC and CIH-exposed groups. In both CIH groups (WT or KO), but not the HC groups, blood pressure increased by 10% at week 1 over their baseline and remained elevated for all 8 wk, with no differences between WT and KO. LV dilation (increased diastolic and systolic dimension) and hypertrophy (increased left heart weight), along with LV dysfunction (greater end-diastolic pressure and lower ejection fraction), were observed in the WT animals compared with the KO following CIH exposure. Compared with HC, CIH exposure was associated with apoptosis (terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling and caspase-3) in WT, but not KO, mice. We conclude that myocardial NCX1 does not mediate changes in blood pressure, but is one of the mediators for LV global dysfunction and cardiomyocyte injury in CIH.
Ling Chen; Jin Zhang; Xuejiao Hu; Kenneth D Philipson; Steven M Scharf
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-14
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  109     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-03-25     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1675-85     Citation Subset:  IM    
Department of Medicine, University of Maryland, Baltimore, Maryland, USA.
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MeSH Terms
Anoxia / complications,  diagnosis,  metabolism*,  pathology,  physiopathology
Blood Pressure
Body Weight
Cardiac Catheterization
Cardiomegaly / etiology,  metabolism
Caspase 3 / metabolism
Chronic Disease
Disease Models, Animal
Gene Expression Regulation
Mice, Inbred C57BL
Mice, Knockout
Myocardium / metabolism*
RNA, Messenger / metabolism
Sodium-Calcium Exchanger / genetics,  metabolism*
Stroke Volume
Time Factors
Ventricular Dysfunction, Left / diagnosis,  etiology,  metabolism*,  pathology,  physiopathology
Ventricular Function, Left*
Grant Support
Reg. No./Substance:
0/NCX1 protein, mouse; 0/RNA, Messenger; 0/Sodium-Calcium Exchanger; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3

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