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At least 289 records · Page 16

All sources NASA NTRS DOE OSTI

DOE OSTI2021

De-ubiquitination of p300 by USP12 Critically Enhances METTL3 Expression and Ang II-induced cardiac hypertrophy

Highlights: • The expression of USP12 is increased in Ang II-induced cardiac hypertrophy in vitro and in vivo. • USP12 aggravates Ang II-induced cardiomyocyte hypertrophy via upregulating METTL3. • USP12 promoted METTL3 expression via modulating p300. • USP12 suppresses the ubiquitination of p300 to block its degradation. Stresses, such as neurohumoral activation, induced pathological cardiac hypertrophy is the main risk factor for heart failure. The ubiquitin-proteasome system (UPS) plays a key role in maintaining protein homeostasis and cardiac function. However, research on the role and mechanism of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is limited. Here, we observe that the deubiquitinating enzyme ubiquitin-specific protease 12(USP12) is upregulated in Ang II-induced hypertrophic hearts and primary neonatal rat cardiomyocytes (NRCMs). Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy, while overexpression of USP12 have the opposite effect. USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo. Moreover, we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3, a methyltransferase which catalyze N{sup 6}-methyladenosine (m{sup 6}A) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy. Upregulation of METTL3 reverse the reduction of myocardial hypertrophy induced by USP12 silencing in NRCMs. In contrast, knockdown of METTL3 attenuate the aggravation of myocardial hypertrophy in USP12-overexpressing NRCMs. Furthermore, we discover that USP12 promote the expression of METTL3 via upregulating p300. Mechanistically, USP12 binds and stabilizes p300, thereby activating the transcription of its downstream gene METTL3. Finally, our data show that USP12 is partially dependent on the stabilization of p300 to activate METTL3 expression and promote myocardial hypertrophy. Taken together, our results demonstrate that USP12 acts as a pro-hypertrophic deubiquitinating enzyme via enhancing p300/METTL3 axis, indicating that targeting USP12 could be a potential treatment strategy for pathological cardiac hypertrophy.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2001

[Measurement of left atrial and ventricular volumes in real-time 3D echocardiography. Validation by nuclear magnetic resonance]

The measurement of the left ventricular ejection fraction is important for the evaluation of cardiomyopathy and depends on the measurement of left ventricular volumes. There are no existing conventional echocardiographic means of measuring the true left atrial and ventricular volumes without mathematical approximations. The aim of this study was to test anew real time 3-dimensional echocardiographic system of calculating left atrial and ventricular volumes in 40 patients after in vitro validation. The volumes of the left atrium and ventricle acquired from real time 3-D echocardiography in the apical view, were calculated in 7 sections parallel to the surface of the probe and compared with atrial (10 patients) and ventricular (30 patients) volumes calculated by nuclear magnetic resonance with the simpson method and with volumes of water in balloons placed in a cistern. Linear regression analysis showed an excellent correlation between the real volume of water in the balloons and volumes given in real time 3-dimensional echocardiography (y = 0.94x + 5.5, r = 0.99, p < 0.001, D = -10 +/- 4.5 ml). A good correlation was observed between real time 3-dimensional echocardiography and nuclear magnetic resonance for the measurement of left atrial and ventricular volumes (y = 0.95x - 10, r = 0.91, p < 0.001, D = -14.8 +/- 19.5 ml and y = 0.87x + 10, r = 0.98, P < 0.001, D = -8.3 +/- 18.7 ml, respectively. The authors conclude that real time three-dimensional echocardiography allows accurate measurement of left heart volumes underlying the clinical potential of this new 3-D method.

Non-NASA Center↗

NASA NTRS2001

Left ventricular, systemic arterial, and baroreflex responses to ketamine and TEE in chronically instrumented monkeys

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

Non-NASA Center↗

DOE OSTI2016

Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats

Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, and improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

Cardiac Function After Multimodal Breast Cancer Therapy Assessed With Functional Magnetic Resonance Imaging and Echocardiography Imaging

Purpose: Breast intensity modulated radiation therapy (IMRT) reduces high-dose heart volumes but increases low-dose volumes. We prospectively assessed heart changes after 3D conformal RT (3DCRT) and IMRT for left-sided breast cancer. Heart dose was analyzed individually, 3DCRT patients were moderately exposed, and IMRT was performed only in patients with unacceptably high heart doses upon 3DCRT planning. Methods and Materials: In 49 patients (38 patients received 3DCRT; 11 patients received IMRT; and 20 patients received neoadjuvant or adjuvant chemotherapy) magnetic resonance imaging (MRI) and echocardiography were performed before and at 6, 12, and 24 months after treatment. Results: Mean heart dose for IMRT was 12.9 ± 3.9 Gy versus 4.5 ± 2.4 Gy for 3DCRT. Heart volumes receiving >40 Gy were 2.6% (3DCRT) versus 1.3% (IMRT); doses were >50 Gy only with 3DCRT. Temporary ejection fraction (EF) decrease was observed on MRI after 6 months (63%-59%, P=.005) resolving at 24 months. Only 3 patients had pronounced largely transient changes of EF and left ventricular enddiastolic diameter (LVEDD). Mitral (M) and tricuspid (T) annular plane systolic excursion (MAPSE and TAPSE) were reduced over the whole cohort (still within normal range). After 24 months left ventricular remodeling index decreased in patients receiving chemotherapy (0.80 vs 0.70, P=.028). Neither wall motion abnormalities nor late enhancements were found. On echocardiography, in addition to EF findings that were similar to those on MRI, global strain was unchanged over the whole cohort at 24 months after a transient decrease at 6 and 12 months. Longitudinal strain decreased in the whole cohort after 24 months in some segments, whereas it increased in others. Conclusions: Until 24 months after risk-adapted modern multimodal adjuvant therapy, only subclinical cardiac changes were observed in both 3DCRT patients with inclusion of small to moderate amounts of heart volume in RT tangents and in the patients treated with IMRT and reduced high-dose heart exposure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Specific Anatomic Considerations for Tricuspid Interventions

Purpose of Review: This review discusses the normal anatomy and pathology of the tricuspid valve (TV) and right side of the heart. Emphasis is on those anatomic and pathologic features relevant to interventions intended to restore normal function to the TV in disease states. Recent Findings: TV pathology is less common than aortic and mitral valve pathology, and treatment and outcomes for interventions face considerable hurdles. New innovations and early data showing safety and efficacy in transcatheter interventions have transformed TV interventions into the next frontier in cardiac valve disease treatment. Certain features of the TV and right heart have presented themselves as potential targets, as well as impediments, for TV intervention. Summary: The causes of TV pathology and the anatomy of the TV and right heart bring unique challenges to intervention. Approaches to intervention will continue to progress and change the way we view and treat TV pathology.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NASA NTRS2000

Fractal correlation properties of R-R interval dynamics and mortality in patients with depressed left ventricular function after an acute myocardial infarction

BACKGROUND: Preliminary data suggest that the analysis of R-R interval variability by fractal analysis methods may provide clinically useful information on patients with heart failure. The purpose of this study was to compare the prognostic power of new fractal and traditional measures of R-R interval variability as predictors of death after acute myocardial infarction. METHODS AND RESULTS: Time and frequency domain heart rate (HR) variability measures, along with short- and long-term correlation (fractal) properties of R-R intervals (exponents alpha(1) and alpha(2)) and power-law scaling of the power spectra (exponent beta), were assessed from 24-hour Holter recordings in 446 survivors of acute myocardial infarction with a depressed left ventricular function (ejection fraction </=35%). During a mean+/-SD follow-up period of 685+/-360 days, 114 patients died (25.6%), with 75 deaths classified as arrhythmic (17.0%) and 28 as nonarrhythmic (6.3%) cardiac deaths. Several traditional and fractal measures of R-R interval variability were significant univariate predictors of all-cause mortality. Reduced short-term scaling exponent alpha(1) was the most powerful R-R interval variability measure as a predictor of all-cause mortality (alpha(1) <0.75, relative risk 3.0, 95% confidence interval 2.5 to 4.2, P<0.001). It remained an independent predictor of death (P<0.001) after adjustment for other postinfarction risk markers, such as age, ejection fraction, NYHA class, and medication. Reduced alpha(1) predicted both arrhythmic death (P<0.001) and nonarrhythmic cardiac death (P<0.001). CONCLUSIONS: Analysis of the fractal characteristics of short-term R-R interval dynamics yields more powerful prognostic information than the traditional measures of HR variability among patients with depressed left ventricular function after an acute myocardial infarction.

Non-NASA Center↗

NASA NTRS2000

Physiological basis for human autonomic rhythms

Oscillations of arterial pressures, heart periods, and muscle sympathetic nerve activity have been studied intensively in recent years to explore otherwise obscure human neurophysiological mechanisms. The best-studied rhythms are those occurring at breathing frequencies. Published evidence indicates that respiratory fluctuations of muscle sympathetic nerve activity and electrocardiographic R-R intervals result primarily from the action of a central 'gate' that opens during expiration and closes during inspiration. Parallel respiratory fluctuations of arterial pressures and R-R intervals are thought to be secondary to arterial baroreflex physiology: changes in systolic pressure provoke changes in the R-R interval. However, growing evidence suggests that these parallel oscillations result from the influence of respiration on sympathetic and vagal-cardiac motoneurones rather than from baroreflex physiology. There is a rapidly growing literature on the use of mathematical models of low- and high-frequency (respiratory) R-R interval fluctuations in characterizing instantaneous 'sympathovagal balance'. The case for this approach is based primarily on measurements made with patients in upright tilt. However, the strong linear relation between such measures as the ratio of low- to high-frequency R-R interval oscillations and the angle of the tilt reflects exclusively the reductions of the vagal (high-frequency) component. As the sympathetic component does not change in tilt, the low- to high-frequency R-R interval ratio provides no proof that sympathetic activity increases. Moreover, the validity of extrapolating from measurements performed during upright tilt to measurements during supine rest has not been established. Nonetheless, it is clear that measures of heart rate variability provide important prognostic information in patients with cardiovascular diseases. It is not known whether reduced heart rate variability is merely a marker for the severity of disease or a measurement that identifies functional reflex abnormalities contributing to terminal dysrhythmias.

Review, Tutorial↗

DOE OSTI2017

Fast myocardial perfusion imaging with {sup 99m}Tc in challenging patients using conventional SPECT cameras

Background: We attempted to validate the performance of a fast myocardial perfusion imaging (MPI) protocol in diagnostically challenging patients. Methods: 78 patients with ΒΜΙ > 24.9, LVH or three vessels disease underwent two sequential gated-MPI studies. The first at 15 (Early Imaging, EI) and the second at 45 (Late Imaging, LI) minutes post {sup 99m}Tc-injection, at both stress and rest. Counts over heart (H), liver (Liv) and subdiaphragmatic space (Sub) and image quality, and myocardial perfusion and function parameters were compared between the two protocols. Coronary angiography was performed within 2 months from MPI, and ROC analysis was used to compare the diagnostic accuracy for the detection of ≥50% diameter luminal stenosis. Results: Quality was optimal-good in 93% of EI and 98% of LI studies (P = .12), H/Liv and stress H/Sub ratios were similar, but rest H/Sub ratio was lower in EI (P = .009). SSS [10 (0 to 46) vs 9 (0 to 36), P = .006] and SDS [3 (0 to 35) vs 2 (0 to 34), P = .02] were higher in EI protocol. LVEF, motion and thickening scores did not differ between the two protocols. A highly significant (P < .001) linear relationship with clinically negligible mean differences in Bland-Altman analysis was observed for all perfusion and function-related data. Sensitivity (EI 81%, LI 80%) and specificity (65% for both) did not differ (P = .23) between the two protocols. Conclusion: The fast protocol is technically feasible and diagnostically accurate compared to the established protocol in diagnostically challenging patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2024

Generalized Quantum Signal Processing

Quantum signal processing (QSP) and quantum singular value transformation (QSVT) currently stand as the most efficient techniques for implementing functions of block-encoded matrices, a central task that lies at the heart of most prominent quantum algorithms. However, current QSP approaches face several challenges, such as the restrictions imposed on the family of achievable polynomials and the difficulty of calculating the required phase angles for specific transformations. In this paper, we present a generalized quantum signal processing (GQSP) approach, employing general SU(2) rotations as our signal-processing operators, rather than relying solely on rotations in a single basis. Our approach lifts all practical restrictions on the family of achievable transformations, with the sole remaining condition being that | P | ≤ 1 , a restriction necessary due to the unitary nature of quantum computation. Furthermore, GQSP provides a straightforward recursive formula for determining the rotation angles needed to construct the polynomials in cases where P and Q are known. In cases where only P is known, we provide an efficient optimization algorithm capable of identifying in under a minute of GPU time, a corresponding Q for polynomials of degree on the order of 10 7 . We further illustrate GQSP simplifies QSP-based strategies for Hamiltonian simulation, offer an optimal solution to the ϵ -approximate fractional query problem that requires O ( ( 1 / δ ) + log ( 1 / ϵ ) ) queries to perform where O ( 1 / δ ) is a proved lower bound, and introduces novel approaches for implementing bosonic operators. Moreover, we propose a novel framework for the implementation of normal matrices, demonstrating its applicability through synthesis of diagonal matrices, as well as the development of a new algorithm for convolution through synthesis of circulant matrices using only O ( d log N + log 2 N ) 1 and 2-qubit gates for a filter of lengths d . Published by the American Physical Society 2024

Motlagh, Danial↗

NASA NTRS1992

Oxygen transport and cardiovascular function at extreme altitude: lessons from Operation Everest II

Operation Everest II was designed to examine the physiological responses to gradual decompression simulating an ascent of Mt Everest (8,848 m) to an inspired PO2 of 43 mmHg. The principal studies conducted were cardiovascular, respiratory, muscular-skeletal and metabolic responses to exercise. Eight healthy males aged 21-31 years began the "ascent" and six successfully reached the "summit", where their resting arterial blood gases were PO2 = 30 mmHg and PCO2 = 11 mmHg, pH = 7.56. Their maximal oxygen uptake decreased from 3.98 +/- 0.2 L/min at sea level to 1.17 +/- 0.08 L/min at PIO2 43 mmHg. The principal factors responsible for oxygen transport from the atmosphere to tissues were (1) Alveolar ventilation--a four fold increase. (2) Diffusion from the alveolus to end capillary blood--unchanged. (3) Cardiac function (assessed by hemodynamics, echocardiography and electrocardiography)--normal--although maximum cardiac output and heart rate were reduced. (4) Oxygen extraction--maximal with PvO2 14.8 +/- 1 mmHg. With increasing altitude maximal blood and muscle lactate progressively declined although at any submaximal intensity blood and muscle lactate was higher at higher altitudes.

Non-NASA Center↗

NASA NTRS2014

Contributions of Astronauts Aerobic Exercise Intensity and Time on Change in VO2peak during Spaceflight

There is considerable variability among astronauts with respect to changes in maximal aerobic capacity (VO2peak) during International Space Station (ISS) missions, ranging from a 5% increase to 30% decline. Individual differences may be due to in-flight aerobic exercise time and intensity. PURPOSE: To evaluate the effects of in-flight aerobic exercise time and intensity on change in VO2peak during ISS missions. METHODS: Astronauts (N=11) performed peak cycle tests approx 60 days before flight (L-60), on flight day (FD) approx 14, and every approx 30 days thereafter. Metabolic gas analysis and heart rate (HR) were measured continuously during the test using the portable pulmonary function system. HR and duration of each in-flight cycle ergometer and treadmill (TM) session were recorded and averaged in time segments corresponding to each peak test. Mixed effects linear regression with exercise mode (TM or cycle) as a categorical variable was used to assess the contributions of exercise intensity (%time >70% peak HR or %time >90% peak HR) and time (min/wk), adjusted for body weight, on %change in VO2peak during the mission, and incorporating the repeated-measures experimental design. RESULTS: 110 observations were included in the model (4-6 peak cycle tests per astronaut, 2 exercise devices). VO2peak was reduced from preflight throughout the mission (FD14: 13+/-13% and FD 105: 8+/-10%). Exercise intensity (%peak HR: FD14=66+/-14; FD105=75+/-8) and time (min/wk: FD14=82+/-46; FD105=158+/-40) increased during flight. The models showed main effects for exercise time and intensity with no interactions between time, intensity, and device (70% peak HR: time [z-score=2.39; P=0.017], intensity [z-score=3.51; P=0.000]; 90% peak HR: time [zscore= 3.31; P=0.001], intensity [z-score=2.24; P=0.025]). CONCLUSION: Exercise time and intensity independently contribute to %change in VO2peak during ISS missions, indicating that there are minimal values for exercise time and intensity required to maintain VO2peak. As the FD105 average exercise intensity and time did not prevent a decline in VO2peak from preflight, astronauts' exercise prescriptions should target at least 160 min of weekly aerobic exercise at an average above 75% peak HR with increased time at intensities above 90% of peak HR starting early in the mission.

Downs, Meghan E.↗

DOE OSTI2019

Is there a role for cardiac positron emission tomography in hypertrophic cardiomyopathy?

Coronary microvascular dysfunction and, its functional consequence, myocardial ischemia are common pathologic features in patients with hypertrophic cardiomyopathy (HCM). Both have been commonly invoked as potential triggers of and/or contributors to the underlying pathophysiological processes leading to heart failure, and malignant ventricular arrhythmias. Positron emission tomography (PET) with myocardial blood flow quantification provides a unique opportunity to evaluate the integrity and function of the coronary microcirculation in HCM. The purpose of the present review is to summarize all the pertinent literature and future perspectives of the role of PET in the evaluation and risk stratification of patients with HCM.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Emerging imaging targets for infiltrative cardiomyopathy: Inflammation and fibrosis

Molecular imaging in infiltrative cardiomyopathies is increasingly penetrating the clinical arena. Current approaches target the infiltrate directly, or its metabolic, physiologic, or functional consequences. Inflammation may not just play a role as the infiltrative mechanism itself. It is also thought to play a key role in the development and progression of heart failure in general, because it promotes the development of tissue fibrosis. The cascade leading from tissue damage to inflammation and further to fibrosis and loss of function has emerged as a therapeutic target. This review focuses (1) on novel tracers of inflammation, which are on the brink of clinical applicability and may be more specific than the gross metabolic marker F-18 deoxyglucose; and (2) on novel biologic imaging targets in fibrosis, which may be exploited for interrogation of the crosstalk between inflammation and loss of contractile function. Ultimately, the success of any novel molecular imaging assay will depend on whether it can be used for successful guidance of novel, targeted therapies aiming at tissue regeneration.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NASA NTRS1972

The use of computer graphic techniques for the determination of ventricular function.

Description of computer techniques employed to increase the speed, accuracy, reliability, and scope of angiocardiographic analyses determining human heart dimensions. Chamber margins are traced with a Calma 303 digitizer from projections of the angiographic films. The digitized margins of the ventricular images are filed in a computer for subsequent analysis. The margins can be displayed on the television screen of a graphics unit for individual study or they can be viewed in real time (or at any selected speed) to study dynamic changes in the chamber outline. The construction of three dimensional images of the ventricle is described.

Sandler, H.↗

NASA NTRS1972

Coronary flow and left ventricular function during environmental stress.

A canine model was used to study the effects of different environmental stresses on the heart and coronary circulation. The heart was surgically instrumented to measure coronary blood flow, left ventricular pressure, and other cardiovascular variables. Coronary flow was recorded by telemetry. Physiologic data were processed and analyzed by analog and digital computers. By these methods the physiologic response to altitude hypoxia, carbon monoxide, hypercapnia, acceleration, exercise, and the interaction of altitude hypoxia and carbon monoxide were described. The effects of some of these stresses on the heart and coronary circulation are discussed.

Erickson, H. H.↗

DOE OSTI2019

Hybrid anatomo-functional imaging of coronary artery disease: Beneficial irrespective of its core components

Coronary artery disease (CAD) is the most common and important cause of ischemic heart disease, with major implications on global morbidity and mortality. Non-invasive testing is crucial in the diagnostic and prognostic work-up of patients with or at risk of CAD, and also to guide decision making in terms of pharmacologic and revascularization therapy. The traditional paradigm is to view anatomic (i.e., coronary computed tomography) and functional imaging (e.g., myocardial perfusion scintigraphy) tests as opposing alternatives. Such approach is too reductionist and does not capitalize on the strengths of each type of test while risking to overlook the inherent limitations. The combination of anatomic and functional tests in a logic of hybrid imaging holds the promise of overcoming the limitations inherent to anatomic and functional testing, enabling more accurate diagnosis, prognosis, and guidance for revascularization in patients with CAD.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NASA NTRS2000

Identification of genes regulated during mechanical load-induced cardiac hypertrophy

Cardiac hypertrophy is associated with both adaptive and adverse changes in gene expression. To identify genes regulated by pressure overload, we performed suppressive subtractive hybridization between cDNA from the hearts of aortic-banded (7-day) and sham-operated mice. In parallel, we performed a subtraction between an adult and a neonatal heart, for the purpose of comparing different forms of cardiac hypertrophy. Sequencing more than 100 clones led to the identification of an array of functionally known (70%) and unknown genes (30%) that are upregulated during cardiac growth. At least nine of those genes were preferentially expressed in both the neonatal and pressure over-load hearts alike. Using Northern blot analysis to investigate whether some of the identified genes were upregulated in the load-independent calcineurin-induced cardiac hypertrophy mouse model, revealed its incomplete similarity with the former models of cardiac growth. Copyright 2000 Academic Press.

NASA Discipline Cardiopulmonary↗