Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload

Ping Hu; Dongfang Zhang; LeAnne Swenson; Gopa Chakrabarti; E Dale Abel; Sheldon E Litwin

doi:10.1152/ajpheart.00108.2003

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Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload

Journal article

Peer reviewed

Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload

Ping Hu, Dongfang Zhang, LeAnne Swenson, Gopa Chakrabarti, E Dale Abel and Sheldon E Litwin

American journal of physiology. Heart and circulatory physiology, Vol.285(3), pp.H1261-1269

09/2003

DOI: 10.1152/ajpheart.00108.2003

PMID: 12738623

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Abstract

We developed a minimally invasive method for producing left ventricular (LV) pressure overload in mice. With the use of this technique, we quickly and reproducibly banded the transverse aorta with low surgical morbidity and mortality. Minimally invasive transverse aortic banding (MTAB) acutely and chronically increased LV systolic pressure, increased heart weight-to-body weight ratio, and induced myocardial fibrosis. We used this technique to determine whether reduced insulin signaling in the heart altered the cardiac response to pressure overload. Mice with cardiac myocyte-restricted knockout of the insulin receptor (CIRKO) have smaller hearts than wild-type (WT) controls. Four weeks after MTAB, WT and CIRKO mice had comparably increased LV systolic pressure, increased cardiac mass, and induction of mRNA for beta-myosin heavy chain and atrial natriuretic factor. However, CIRKO hearts were more dilated, had depressed LV systolic function by echocardiography, and had greater interstitial fibrosis than WT mice. Expression of connective tissue growth factor was increased in banded CIRKO hearts compared with WT hearts. Thus lack of insulin signaling in the heart accelerates the transition to a more decompensated state during cardiac pressure overload. The use of the MTAB approach should facilitate the study of the pathophysiology and treatment of pressure-overload hypertrophy.

Blood Pressure

Myocardial Contraction

Hypertrophy, Left Ventricular - metabolism

Mice, Inbred C57BL

Male

Myocytes, Cardiac - pathology

Insulin - metabolism

Animals

Hypertrophy, Left Ventricular - pathology

Aorta - surgery

Fibrosis

Myocytes, Cardiac - metabolism

Signal Transduction - physiology

Mice

Ventricular Pressure

Hypertrophy, Left Ventricular - physiopathology

Disease Models, Animal

Details

Title: Subtitle: Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload
Creators: Ping Hu - Division of Cardiology, University Hospital, The University of Utah, 50 N. Medical Drive, Salt Lake City, UT 84132, USA
Dongfang Zhang
LeAnne Swenson
Gopa Chakrabarti
E Dale Abel
Sheldon E Litwin
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.285(3), pp.H1261-1269
Publisher: United States
DOI: 10.1152/ajpheart.00108.2003
PMID: 12738623
ISSN: 0363-6135
eISSN: 1522-1539
Grant note: DK 58073 / NIDDK NIH HHS HL 52338-06 / NHLBI NIH HHS U01 70525 / PHS HHS T32 HL 7576 / NHLBI NIH HHS R01 DK092065 / NIDDK NIH HHS
Language: English
Date published: 09/2003
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024536202771

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