Echocardiographic assessment of age-associated changes in systolic and diastolic function of the female F344 rat heart

Boluyt, Marvin O.; Converso, Kimber; Hwang, Hyun Seok; Mikkor, Agdas; Russell, Mark W.

doi:10.1152/japplphysiol.01026.2003

Cited by 81 publications

(84 citation statements)

References 13 publications

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“…However, in the current study, the effect of aging per se on myocardial structure, function, and protein metabolism under basal conditions in female F344 rats was nominal. These data differ from those reported by Boluyt et al (5) in which female F344 rats showed a more marked age-associated increase in LV end-diastolic and end-systolic volume and dimension and decrease in fractional shortening and ejection fraction. There are two major differences between this and the current study.…”

Section: Discussioncontrasting

confidence: 99%

“…First, in Boluyt et al (5), changes were detected when aged rats were compared with 4-mo-old animals, whereas our comparison group of adult rats were 4 mo of age when placed on the alcohol-containing diet but 8 mo of age when cardiovascular and metabolic endpoints were assessed. Moreover, the cardiac dysfunction noted by Boluyt et al (5) was more pronounced at 30 mo compared with 22 mo, the time point used in our current study. Hence, the conclusion reached may depend not only on the absolute age of the old animals, but also on the age of the adult rats to which they are compared.…”

Section: Discussionsupporting

confidence: 45%

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Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats

Lang

2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Lang CH, Korzick DH. Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats. Am J Physiol Regul Integr Comp Physiol 306: R23-R33, 2014. First published November 13, 2013 doi:10.1152/ajpregu.00414.2013.-The purpose of this study was to assess whether the deleterious effect of chronic alcohol consumption differs in adult and aged female rats. To address this aim, adult (4 mo) and aged (18 mo) F344 rats were fed a nutritionally complete liquid diet containing alcohol (36% total calories) or an isocaloric isonitrogenous control diet for 20 wk. Cardiac structure and function, assessed by echocardiography, as well as myocardial protein synthesis and proteolysis did not differ in either alcohol-versus control-fed adult rats or in adult versus aged controlfed rats. In contrast, cardiac function was impaired in alcohol-fed aged rats compared with age-matched control rats. Additionally, alcohol feeding decreased cardiac protein synthesis that was associated with decreased phosphorylation of 4E-BP1 and S6K1. This reduction in mammalian target of rapamycin (mTOR) kinase activity was associated with reduced eIF3f and binding of both Raptor and eIF4G to eIF3. Proteasome activity was increased in alcohol-fed aged rats with a coordinate elevation in the E3 ligases atrogin-1 and muscle RINGfinger protein-1 (MuRF1). These changes were associated with increased regulated in development and DNA damage response 1 (REDD1) and phosphorylation of AMP-activated protein kinase (AMPK) but no increase in AKT or forkhead transcription factor (FOXO)3 phosphorylation. Finally, markers of autophagy (e.g., LC3B, Atg7, Atg12) and TNF-␣ were increased to a greater extent in alcohol-fed aged rats. These data demonstrate that aged female rats exhibit an enhanced sensitivity to alcohol compared with adult animals. Our data are consistent with a model whereby alcohol increases proteolysis via FOXO-independent increase in atrogin-1, which degrades eIF3f and therefore impairs formation of a functional preinitiation complex and protein synthesis.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 45%

Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats

Lang

2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Mice were sedated with 1.5% isoflurane and placed in a supine position. Two-dimensionally guided M-mode recordings were obtained by an experienced operator as previously described (4). Scans were from a short-axis view at the level of the papillary muscles with either an Acuson Sequoia system with an Acuson 15-MHz linear-array transducer or a GE Vivid 7 system with a GE S10-MHz phased-array transducer (General Electric).…”

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Pleiotropic Phenotype of a Genomic Knock-In of an RGS-Insensitive G184S Gnai2 Allele

Huang

Charbeneau

et al. 2006

Molecular and Cellular Biology

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101

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Signal transduction via guanine nucleotide binding proteins (G proteins) is involved in cardiovascular, neural, endocrine, and immune cell function. Regulators of G protein signaling (RGS proteins) speed the turn-off of G protein signals and inhibit signal transduction, but the in vivo roles of RGS proteins remain poorly defined. To overcome the redundancy of RGS functions and reveal the total contribution of RGS regulation at the G␣ i2 subunit, we prepared a genomic knock-in of the RGS-insensitive G184S Gnai2 allele. The G␣ i2 G184S knock-in mice show a dramatic and complex phenotype affecting multiple organ systems (heart, myeloid, skeletal, and central nervous system). Both homozygotes and heterozygotes demonstrate reduced viability and decreased body weight. Other phenotypes include shortened long bones, a markedly enlarged spleen, elevated neutrophil counts, an enlarged heart, and behavioral hyperactivity. Heterozygous G␣ i2 ؉/G184S mice show some but not all of these abnormalities. Thus, loss of RGS actions at G␣ i2 produces a dramatic and pleiotropic phenotype which is more evident than the phenotype seen for individual RGS protein knockouts.Cell-cell communication is fundamental to the maintenance of homeostasis. The G protein-coupled receptor superfamily is arguably the most abundant and diverse protein family in cellular signaling and is tightly regulated. A novel family of Ͼ20 proteins termed regulators of G protein signaling, or RGS proteins, both tonically inhibit G protein function and also serve as signal control points (2,22,34,39,69). RGS-mediated inhibition of G protein signaling occurs through direct binding of the RGS protein to the G␣ subunit, with subsequent GTPase-accelerating protein (GAP) actions to rapidly deactivate G␣ (2). Deactivation may be accelerated up to 1,000-fold and shuts down both G␣ and G␤␥ signals (42, 48). RGS proteins may also competitively inhibit G␣ binding to effectors such as phospholipase C (32). Most of the currently known RGS proteins interact with either Gi or Gq family G proteins and influence cyclic AMP (cAMP), Ca 2ϩ , mitogen-activated protein kinase, and ion channel signaling. There is strong evidence implicating them in the subsecond kinetics of G i -and G o -mediated ion channel activation and deactivation in the heart (10, 21, 36) and neurons (36). In addition, the conserved RGS domain has been found to serve as a multifunctional protein adapter which can recruit many effectors or regulators to the vicinity of activated G proteins (31,53,62). Notable examples include p115rhoGEF (30, 40) and GRK2 (44). There is also emerging interest in RGS proteins as drug targets (9,20,53,72).However, the physiological functions of RGS proteins remain poorly defined. A number of RGS knockouts have been reported (for example, RGS1, -2, -4, and -9). The RGS9-1 knockout shows prolonged visual potentials (7), and RGS9-2 disruption results in markedly enhanced responses to drugs of abuse, such as cocaine, amphetamines, and opiates (56, 71). A human disorder, bradyopsia, with r...

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“…The efficacy of echocardiography in the rat model has been confirmed (10,40,41), and it has been used to evaluate treatment effects on cardiac function (34), to assess cardiac structural and functional characteristics of rats with surgically induced myocardial infarct (30) and hypertension (24,32), and in genetic models of hypertrophic heart failure (37). Only recently has there been a report on baseline echocardiographic values for normal adult rats (51) and age-associated changes in the female F344 rat heart (9).Although several studies have characterized the cardiovascular system in older rats (1,5,8,9,14,21,23,33,37), no study has examined functional and structural alterations over 30 mo of age. In this study we determined standard reference values for adult (12 mo) and aging (18 to 39 mo in 3-mo intervals) FBN male rat cardiovascular structure and function by using echocardiographic, hemodynamic, and histological measures.…”

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Age-related changes in cardiac structure and function in Fischer 344 × Brown Norway hybrid rats

Hacker¹,

McKiernan²,

Douglas³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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The effects of aging on cardiovascular function and cardiac structure were determined in a rat model recommended for gerontological studies. A cross-sectional analysis assessed cardiac changes in male Fischer 344 ϫ Brown Norway F1 hybrid rats (FBN) from adulthood to the very aged (n ϭ 6 per 12-, 18-, 21-, 24-, 27-, 30-, 33-, 36-, and 39-mo-old group). Rats underwent echocardiographic and hemodynamic analyses to determine standard values for left ventricular (LV) mass, LV wall thickness, LV chamber diameter, heart rate, LV fractional shortening, mitral inflow velocity, LV relaxation time, and aortic/LV pressures. Histological analyses were used to assess LV fibrotic infiltration and cardiomyocyte volume density over time. Aged rats had an increased LV mass-to-body weight ratio and deteriorated systolic function. LV systolic pressure declined with age. Histological analysis demonstrated a gradual increase in fibrosis and a decrease in cardiomyocyte volume density with age. We conclude that, although significant physiological and morphological changes occurred in heart function and structure between 12 and 39 mo of age, these changes did not likely contribute to mortality. We report reference values for cardiac function and structure in adult FBN male rats through very old age at 3-mo intervals. hybrid rat; echocardiography CARDIAC STRUCTURE AND FUNCTION are remarkably similar among mammalian species, and the use of animal models has been extremely helpful in developing treatment strategies for alleviating heart disease in humans. Extending animal studies beyond young adult ages to very old ages may provide similar benefits to cardiovascular health of the growing aged population. In mammalian tissues, aging manifests as detrimental alterations in structure and function. Structural changes in the aging heart extend from cardiomyocyte cell loss, left ventricular (LV) hypertrophy, changes in ventricle chamber diameter, and collagen deposition (3, 13, 14), leading to overt functional changes such as lengthening of contraction and relaxation times and thus a decrease in heart rate (15), decreases in fractional shortening, decreased LV end-systolic pressure (15, 33), and reduced cardiac output. These normal aging changes do not necessarily contribute to morbidity but are clearly associated with the general decline observed with aging.The Fischer 344 (F344) rat has been a standard model of aging with an extensive database on this genotype (29). Even though the F344 rat has been widely used in research, concerns have been raised whether this specific strain is appropriate for all gerontological studies because of its overuse and some severe age-related pathologies (53). The National Institute on Aging and the National Center for Toxicological Research responded to these concerns and found that, among others, the Fischer 344 ϫ Brown Norway F1 hybrid rat (FBN) would complement the F344 aging studies (53). The FBN rat had significantly fewer pathological lesions compared with the F344 and a greater mean age for 50% mortality...

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Echocardiographic assessment of age-associated changes in systolic and diastolic function of the female F344 rat heart

Cited by 81 publications

References 13 publications

Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats

Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats

Pleiotropic Phenotype of a Genomic Knock-In of an RGS-Insensitive G184S Gnai2 Allele

Age-related changes in cardiac structure and function in Fischer 344 × Brown Norway hybrid rats

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