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

Abstract

imally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload. Am J Physiol Heart Circ Physiol 285: H1261-H1269, 2003. First published May 8, 2003 10.1152/ajpheart.00108. 2003.-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 ␤-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 pressureoverload hypertrophy.hypertrophy; contractility; fibrosis THE ABILITY TO MANIPULATE gene expression in mice has contributed greatly to the study of many diseases. In terms of the heart, the response of genetically altered animals to increased cardiac work (e.g., pressure overload) is of particular interest. Rockman and colleagues (33) pioneered a model of transverse aortic constriction in the mouse. The use of this model has provided significant insight into the cellular and molecular pathways responsible for the development of left ventricular (LV) hypertrophy (LVH). Although transverse aortic constriction in mice is now done routinely by a number of groups, the technical difficulty of the surgical procedure has limited the availability of this model.Previously published methods for the creation of transverse aortic constriction in mice require microsurgical skills and the ability to provide mechanical ventilation when the thorax is entered. The requirement for tracheal intubation and low-volume, high-rate mechanical ventilation mandates additional time and expense associated with these procedures. Moreover, inflammatory reactions within the chest may complicate the analyses of cardiac function and pathology. Herein, we report a minimally invasive transverse aortic banding (MTAB) procedure in mice that obviates the need for providing mechanical ventilation because the pleural space is not entered. The procedure can be performed rapidly and...

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Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway

“…Cardiomyocyte-restricted insulin receptor (IR) KO mice exhibit a decrease in heart size and impaired contractile function (Belke et al 2002), and this small heart phenotype is mediated by attenuated Akt signaling in the heart of IR KO mice . However, in response to pathological hypertrophic stimuli such as pressure overload or isoproterenol infusion, heart size increases in both wild-type and KO mice with similar final heart weight, although the heart size of IR KO mice at baseline is smaller than that of wild-type animals (Hu et al 2003). Thus, intrinsic insulin signaling in the heart is required for normal physiological cardiac growth during postnatal development, but is dispensable for, and may attenuate the development of, pathological hypertrophy.…”

Insulin Resistance and Cardiomyopathy

“…In experimental rodent models, myocardial contractile dysfunction independent of coronary artery disease has also been demonstrated in db/db, ob/ob, and Zucker rodent models, supporting the existence of an obesity-related cardiomyopathy and a diabetic cardiomyopathy (3,22). In addition, mice with a selective cardiomyocyte only deletion of the insulin receptor (CIRKO mice) have reduced insulinstimulated glucose uptake and also have a modest decrease in contractile function, thereby implicating insulin resistance as a contributing factor in the development of contractile dysfunction in the metabolic syndrome (23,24).…”