Noninvasive Cardiovascular Phenotyping in Mice

Hartley, Craig J.; Taffet, George E.; Reddy, Anilkumar K.; Entman, Mark L.; Michael, Lloyd H.

doi:10.1093/ilar.43.3.147

Cited by 64 publications

(48 citation statements)

References 60 publications

(88 reference statements)

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“…Transverse aortic banding was conducted in 12-week-old adult WT and ROCK-1 Ϫ/Ϫ mice, N Ն 6 mice for each group (39). Briefly, both ROCK-1 Ϫ/Ϫ and WT mice received a comparable load, based on the right-to-left carotid artery flow velocity ratio (from 5:1 to 10:1) after constricting the transverse aorta.…”

Section: Methodsmentioning

confidence: 99%

Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis

Chang

Xie²,

Shah

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

204

200

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Rho-associated coiled-coil protein kinase 1 (ROCK-1) is a direct cleavage substrate of activated caspase-3, which is associated with heart failure. In the course of human heart failure, we found marked cleavage of ROCK-1 resulting in a 130-kDa subspecies, which was absent in normal hearts and in an equivalent cohort of patients with left ventricular assist devices. Murine cardiomyocytes treated with doxorubicin led to enhanced ROCK-1 cleavage and apoptosis, all of which was blocked by a caspase-3 inhibitor. In addition, a bitransgenic mouse model of severe cardiomyopathy, which overexpresses Gq protein and hematopoietic progenitor kinase-͞germinal center kinase-like kinase, revealed the robust accumulation of the 130-kDa ROCK-1 cleaved fragment. This constitutively active ROCK-1 subspecies, when expressed in cardiomyocytes, led to caspase-3 activation, indicating a positive feedforward regulatory loop. ROCK-1-dependent caspase-3 activation was coupled with the activation of PTEN and the subsequent inhibition of protein kinase B (Akt) activity, all of which was attenuated by siRNA directed against ROCK-1 expression. Similarly, ROCK-1-null mice (Rock-1 ؊/؊ ) showed a marked reduction in myocyte apoptosis associated with pressure overload. These data suggest an obligatory role for ROCK-1 cleavage in promoting apoptotic signals in myocardial hypertrophy and͞or failure.heart failure ͉ left ventricle assist device ͉ phosphatase and tensin homolog deleted on chromosome ten H eart failure is an eventual outcome for diverse cardiovascular disorders and the leading cause of combined morbidity and mortality in the United States and other developed industrial nations (1). Diverse signal transduction pathways, G proteins and protein kinases among them, likely contribute to heart failure, and the identification of essential control points have both fundamental and translational importance (2, 3). Recent findings suggest a role for the activation of the apoptotic cascade in heart failure, which may involve the activation of proteolytic caspase-3 and cardiomyocyte loss (1, 4). Although the level of apoptosis detected in the failing heart are variable (4-6), a low prevalence of apoptosis is sufficient to cause cardiac contractile depression (7). Accounting for the most conservative rate of cardiomyocyte death, the normal heart would lose most of its mass in a few decades, but the senile and failing heart lose myocytes in a matter of several months to a few years (8). This dilemma raised the issue of the imbalance between the continual loss of cardiomyocytes and the long interval for the chronic progression in heart failure. There are critical deficiencies in the available information regarding the relationship between apoptosis in the failing heart and depressed contractile function. Other mechanisms might contribute to heart failure besides cell loss. For example, we showed that activated caspase-3 mediated the cleavage of serum response factor (SRF). Cleaved SRF became a dominant negative factor that down-regulated SRF target ...

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Section: Methodsmentioning

confidence: 99%

Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis

Chang

Xie²,

Shah

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

204

200

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“…Noninvasive methods are used to study the effects of thyroid hormone on cardiac function and morphology (540,545,546). These methods are ideally suited for longitudinal analyses of individual animals.…”

Section: And Recommendation 49mentioning

confidence: 99%

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Bianco

Anderson

Forrest

et al. 2014

Thyroid

176

106

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“…For noninvasive measurements (including before banding) mice were anesthetized in a closed chamber with 3% isoflurane in oxygen for 2 to 5 minutes until immobile. Each mouse was then removed, weighed, and taped supine to ECG electrodes on a heated procedure board (MousePad, Indus Instruments, Houston, TX, USA) (Hartley et al, 2002) with isoflurane (initially at 2%) supplied by a nose cone connected to an anesthesia machine (Model V-1 with Isoflurane Vaporizer, VetEquip, Pleasanton, CA, USA). The board temperature was maintained at 35-37 °C.…”

Section: Animal Protocolmentioning

confidence: 99%

Doppler Estimation of Reduced Coronary Flow Reserve in Mice with Pressure Overload Cardiac Hypertrophy

Hartley

Reddy

Madala

et al. 2008

Ultrasound in Medicine & Biology

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Aortic banding produces pressure overload cardiac hypertrophy in mice leading to decompensated heart failure in 4-8 wks, but the effects on coronary blood flow velocity and reserve are unknown. To determine whether coronary flow reserve (CFR) was reduced, we used noninvasive 20 MHz Doppler ultrasound to measure left main coronary flow velocity at baseline (B) and at hyperemia (H) induced by low (1%) and high (2.5%) concentrations of isoflurane gas anesthesia. Ten mice were studied before (Pre) and at 1d, 7d, 14d, and 21d after constricting the aortic arch to 0.4 mm diameter distal to the innominate artery. We also measured cardiac inflow and outflow velocities at the mitral and aortic valves and velocity at the jet distal to the aortic constriction. The pressure drop as estimated by 4V 2 at the jet was 51 ± 5.1 (mean ± SE) mmHg at 1d increasing progressively to 74 ± 5.2 mmHg at 21d. Aortic and mitral blood velocities were not significantly different after banding (p = NS), but CFR, as estimated by H/B, dropped progressively from 3.2 ± 0.3 before banding to 2.2 ± 0.4, 1.7 ± 0.3, 1.4 ± 0.2, and 1.1 ± 0.1 at 1d, 7d, 14d, and 21d respectively (all P < 0.01 vs Pre). There was also a significant and progressive increase the systolic/diastolic velocity ratio (0.17 Pre to 0.92 at 21d, all P < 0.01 vs Pre) suggesting a redistribution of perfusion from subendocardium to subepicardium. We show for the first time that CFR, as estimated by the hyperemic response to isoflurane and Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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Noninvasive Cardiovascular Phenotyping in Mice

Cited by 64 publications

References 60 publications

Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis

Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Doppler Estimation of Reduced Coronary Flow Reserve in Mice with Pressure Overload Cardiac Hypertrophy

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