Variations in Energy Metabolism Precede Alterations in Cardiac Structure and Function in Hypertrophic Preconditioning

Recent studies have unveiled that myocardial hypertrophic preconditioning (HP), which is produced by de-banding (De-TAC) of short-term transverse aortic constriction (TAC), protects the heart against hypertrophic responses caused by subsequent re-constriction (Re-TAC) in mice. Although cardiac substrate metabolism is impaired in heart failure, it remains unclear about the role of HP-driven energetics in the development of cardiac hypertrophy. Here, we investigated energy metabolism, cardiac hypertrophy, and function following variational loading conditions, as well as their relationships in HP. Male C57BL/6J mice (10–12 weeks old) were randomly subjected to Sham, HP [TAC for 3days (TAC 3d), de-banding the aorta for 4 days (De-TAC 4d), and then re-banding the aorta for 4 weeks (Re-TAC 4W)], and TAC (TAC for 4 weeks without de-banding). Cardiac echocardiography, hemodynamics, and histology were utilized to evaluate cardiac remodeling and function. The mRNA expression levels of fetal genes (ANP and BNP), glucose metabolism-related genes (glut4, pdk4), and fatty acid oxidation-related genes (mcad, pgc1α, mcd, pparα) were quantitated by real-time quantitative PCR. Activation of hypertrophy regulators ERK1/2, a metabolic stress kinase AMP-activated protein kinase (AMPK), and its downstream target acetyl-coA carboxylase (ACC) were explored by western blot. Compared with TAC 4W mice, Re-TAC 4W mice showed less impairment in glucose and fatty acid metabolism, as well as less cardiac hypertrophy and dysfunction. Moreover, no significant difference was found in myocardial hypertrophy, fibrosis, and cardiac function in TAC 3d and De-TAC 4d groups compared with Sham group. However, glut4, pdk4, mcad, pgc1α, mcd, and pparα were all decreased, while AMPK and ACC were activated in TAC 3d and returned to Sham level in De-TAC 4d, suggesting that the change in myocardial energy metabolism in HP mice was earlier than that in cardiac structure and function. Collectively, HP improves energy metabolism and delays cardiac remodeling, highlighting that early metabolic improvements drive a potential beneficial effect on structural and functional restoration in cardiac hypertrophy.

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Kashmiri Wazwan: Are We Listening to Our Endothelium?

JMS SKIMS ◽

10.33883/jms.v16i2.213 ◽

2013 ◽

Vol 16 (2) ◽

pp. 72-74

Author(s):

M Fuad Jan ◽

Suhail Allaqband

Keyword(s):

Insulin Resistance ◽

Cardiac Remodeling ◽

Experimental Models ◽

Structure And Function ◽

Cardiac Structure ◽

Unsaturated Lipid ◽

Diet Induced Obesity ◽

Blood Pressure Homeostasis ◽

Cardiac Structure And Function ◽

And Function

In animal models of diet-induced obesity, hypercaloric (4.6 Kcal/g) diets have been shown to have metabolic hormonal effects, including hyperglycemia, insulin resistance and changes in leptin profiles 1, as well as undesirable effects on blood pressure homeostasis and even cardiac remodeling. Such effects have been directly and inversely correlated with saturated and unsaturated lipid consumption, respectively. In these experimental models, it also has been elegantly demonstrated that a variety of alterations in cardiac structure and function occur due to reduced myofilament Ca2+ sensitivity, alterations in Ca2+ handling proteins and beta-adrenergic receptors2-5. JMS 2013;16(2):72-74

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Abstract P138: Alterations in Cardiac Structure and Function in Young Adults Born Extremely Preterm: Impact of Neonatal Bronchopulmonary Dysplasia

Hypertension ◽

10.1161/hyp.70.suppl_1.p138 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Muhammad Oneeb Rehman Mian ◽

Jean-Luc Bigras ◽

Rafael Fernandes ◽

Mariane Bertagnolli ◽

Li Feng Xie ◽

...

Keyword(s):

Young Adults ◽

Preterm Birth ◽

Cardiac Remodeling ◽

Structure And Function ◽

Cardiac Structure ◽

Lv Mass ◽

Extremely Preterm ◽

Cardiac Structure And Function ◽

And Function

Objective: Studies support a causal association between preterm birth and increased risk of cardiovascular diseases. Increased left and right ventricular mass and impaired systolic and diastolic function has been reported in young adults born preterm. However, the impact of extreme preterm birth and prematurity-specific complications on adult cardiac structure and function has not been evaluated. We assessed cardiac structure and function in young adults born extremely preterm (EPT) versus term, and correlated long term cardiac remodeling with neonatal bronchopulmonary dysplasia (BPD). Methods: Eighty five EPT (gest. age = 27.1±1.4 weeks) were recruited along with term-born controls matched for age, sex and socioeconomic status. Birth and neonatal data (gestational age, birth weight, BPD indicated by O 2 requirements at 36 weeks postmenstrual age) was collected. Ambulatory blood pressure (Spacelabs) and echocardiographic measurements (Phillips) were taken. Comparisons were performed using ANOVA or T-test. Results: EPT presented with increased systolic (119±9 vs 116±8 mmHg, P<0.05) and diastolic (68±5 vs 66±6 mmHg, P<0.05) blood pressures. EPT exhibited reduced septal thickness (IVS, 6.8±0.8 vs 7.1±1.1 mm, P<0.05), left ventricular internal dimension (LVID, 46±4 vs 48±5 mm, P<0.05), LV end-diastolic (98±20 vs 106±24 ml, P<0.05) and end-systolic (36±9 vs 40±11 ml, P<0.01) volumes, right ventricular internal dimension (RVID, 22±3 vs 24±4 mm, P<0.05), and LV mass (104±27 vs 115±30 g, P<0.05), but similar LV mass and volume indexes. EPT exhibited increased LV myocardial performance index (0.41±0.04 vs 0.39±0.04, P<0.01), reduced mitral lateral e’ (17.6±2.8 vs 19.1±2.6 cm/s, P<0.01), mitral s’ (10.7±2.3 vs 11.6±2.3 cm/s, P<0.01), tricuspid E’ (15.8±2.7 vs 16.8±2.1 cm/s, P<0.05), and tricuspid S’ (13.1±2.0 vs 14.0±2.0 cm/s, P<0.01) waves, and a trend in reduced mitral E wave (81±14 vs 85±15 cm/s, P=0.09). EPT with neonatal BPD exhibited greater reduction in IVS (6.5±0.8 mm, P<0.05 vs terms), LVID (45±4 mm, P<0.05), LV Mass (98±22 g, P<0.05), and RVID (20±3 mm, P<0.01). Conclusions: EPT exhibit cardiac structural and functional alterations compared to term-born individuals. Neonatal BPD in EPT is a key contributor to long term cardiac remodeling.

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Abstract 193: Multiple Prior Live Births Are Associated With Cardiac Remodeling and Heart Failure in Women

Circulation ◽

10.1161/circ.142.suppl_3.193 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Amy Sarma ◽

Samantha Paniagua ◽

Elizabeth Liu ◽

Emily Lau ◽

Martin Larson ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Remodeling ◽

Structure And Function ◽

Cardiovascular Health Study ◽

Cardiac Structure ◽

Live Births ◽

Nulliparous Women ◽

Increased Risk ◽

Cardiac Structure And Function ◽

And Function

Introduction: Greater parity has been associated with increased risk of cardiovascular disease, though effects on cardiac remodeling and heart failure risk remain unclear. Hypothesis: We hypothesized that multiple prior live births are associated with (1) structural and functional cardiac remodeling and (2) risk of future heart failure. Methods: We examined the association of number of live births and echocardiographic measures of cardiac structure and function in women participants of the Framingham Heart Study (FHS) using multivariable linear regression. We next examined the association of parity with incident heart failure (HFpEF, HFrEF) using Cox models in a pooled analysis of n=10,431 participants of FHS, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis. Results: Among n=3931 FHS participants (mean age 48 ± 13 years), higher number of live births was associated with worse LV fractional shortening (multivariable β -1.11 (0.31), p= 0.0005 in ≥ 5 live births vs nulliparous women, p trend= 0.02, Figure ). In addition, greater parity was associated with worse cardiac mechanics including global circumferential strain and longitudinal and radial dyssynchrony (p< 0.01 for all comparing ≥ 5 live births vs nulliparity). Over a mean follow-up of 11.7 ± 3.2 years, 298 HFpEF and 225 HFrEF events occurred. Women with ≥5 live births were at higher risk of developing future HFrEF compared with nulliparous women (HR 1.93, 95% CI 1.19-3.12, p=0.008); by contrast, a lower risk of HFpEF was observed (HR 0.58, 95% CI 0.37-0.91, p=0.02, p trend= 0.04). Conclusions: Greater number of live births are associated with worse cardiac structure and function, as well as increased risk of incident HFrEF. Further studies are needed to better understand mechanisms by which repeated pregnancies portend adverse cardiovascular risk.

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Normalization of cardiac structure and function after regression of cardiac hypertrophy

American Heart Journal ◽

10.1016/0002-8703(94)90487-1 ◽

1994 ◽

Vol 128 (2) ◽

pp. 333-343 ◽

Cited By ~ 16

Author(s):

Gabriel B. Habib ◽

Douglas L. Mann ◽

William A. Zoghbi

Keyword(s):

Cardiac Hypertrophy ◽

Structure And Function ◽

Cardiac Structure ◽

Cardiac Structure And Function ◽

Regression Of Cardiac Hypertrophy ◽

And Function

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Omega-3 fatty acid prevents the development of heart failure by changing fatty acid composition in the heart

Scientific Reports ◽

10.1038/s41598-020-72686-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Haruhiro Toko ◽

Hiroyuki Morita ◽

Masanori Katakura ◽

Michio Hashimoto ◽

Toshiyuki Ko ◽

...

Keyword(s):

Fatty Acid ◽

Pressure Overload ◽

Structure And Function ◽

Free Form ◽

Cardiac Structure ◽

Omega 3 ◽

Omega 3 Fatty Acid ◽

Beneficial Effects ◽

Cardiac Structure And Function ◽

And Function

Abstract Some clinical trials showed that omega-3 fatty acid (FA) reduced cardiovascular events, but it remains unknown whether omega-3 FA supplementation changes the composition of FAs and their metabolites in the heart and how the changes, if any, exert beneficial effects on cardiac structure and function. To clarify these issues, we supplied omega-3 FA to mice exposed to pressure overload, and examined cardiac structure and function by echocardiography and a proportion of FAs and their metabolites by gas chromatography and liquid chromatography-tandem mass spectrometry, respectively. Pressure overload induced cardiac hypertrophy and dysfunction, and reduced concentration of all FAs’ components and increased free form arachidonic acid and its metabolites, precursors of pro-inflammatory mediators in the heart. Omega-3 FA supplementation increased both total and free form of eicosapentaenoic acid, a precursor of pro-resolution mediators and reduced free form arachidonic acid in the heart. Omega-3 FA supplementation suppressed expressions of pro-inflammatory cytokines and the infiltration of inflammatory cells into the heart and ameliorated cardiac dysfunction and fibrosis. These results suggest that omega-3 FA-induced changes of FAs composition in the heart have beneficial effects on cardiac function via regulating inflammation.

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Temporal Measures in Cardiac Structure and Function During the Development of Obesity Induced by Different Types of Western Diet in a Rat Model

Nutrients ◽

10.3390/nu12010068 ◽

2019 ◽

Vol 12 (1) ◽

pp. 68 ◽

Cited By ~ 1

Author(s):

Danielle Fernandes Vileigas ◽

Cecília Lume de Carvalho Marciano ◽

Gustavo Augusto Ferreira Mota ◽

Sérgio Luiz Borges de Souza ◽

Paula Grippa Sant’Ana ◽

...

Keyword(s):

Cardiac Remodeling ◽

Systolic Function ◽

Control Diet ◽

Structure And Function ◽

Western Diet ◽

Cardiac Structure ◽

Different Types ◽

Cardiac Structure And Function ◽

And Function

Obesity is recognized worldwide as a complex metabolic disorder that has reached epidemic proportions and is often associated with a high incidence of cardiovascular diseases. To study this pathology and evaluate cardiac function, several models of diet-induced obesity (DIO) have been developed. The Western diet (WD) is one of the most widely used models; however, variations in diet composition and time period of the experimental protocol make comparisons challenging. Thus, this study aimed to evaluate the effects of two different types of Western diet on cardiac remodeling in obese rats with sequential analyses during a long-term follow-up. Male Wistar rats were distributed into three groups fed with control diet (CD), Western diet fat (WDF), and Western diet sugar (WDS) for 41 weeks. The animal nutritional profile and cardiac histology were assessed at the 41st week. Cardiac structure and function were evaluated by echocardiogram at four different moments: 17, 25, 33, and 41 weeks. A noninvasive method was performed to assess systolic blood pressure at the 33rd and 41st week. The animals fed with WD (WDF and WDS) developed pronounced obesity with an average increase of 86.5% in adiposity index at the end of the experiment. WDF and WDS groups also presented hypertension. The echocardiographic data showed no structural differences among the three groups, but WDF animals presented decreased endocardial fractional shortening and ejection fraction at the 33rd and 41st week, suggesting altered systolic function. Moreover, WDF and WFS animals did not present hypertrophy and interstitial collagen accumulation in the left ventricle. In conclusion, both WD were effective in triggering severe obesity in rats; however, only the WDF induced mild cardiac dysfunction after long-term diet exposure. Further studies are needed to search for an appropriate DIO model with relevant cardiac remodeling.

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Changes in cardiac structure and function with aging

10.20517/jca.2021.40 ◽

2022 ◽

Author(s):

Tanushree Agrawal ◽

Sherif F. Nagueh

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Cardiac Remodeling ◽

Structure And Function ◽

Cardiac Structure ◽

Physiological Changes ◽

Age Related ◽

Cardiac Structure And Function ◽

And Function

Aging is associated with progressive changes in cardiac structure and function. The prevalence of cardiovascular risk factors and disease also increases profoundly with advancing age. Therefore, understanding the spectrum of physiological changes in the aging heart is crucial for the identification and risk stratification of cardiovascular disease. In this review, we discuss echocardiographic features of age-related cardiac remodeling.

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Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00852.2006 ◽

2007 ◽

Vol 292 (5) ◽

pp. H2138-H2143 ◽

Cited By ~ 87

Author(s):

Danijel Juric ◽

Peter Wojciechowski ◽

Dipak K. Das ◽

Thomas Netticadan

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Cardiac Hypertrophy ◽

Wall Thickness ◽

Structure And Function ◽

Cardiac Structure ◽

Aortic Banding ◽

Cardiac Structure And Function ◽

And Function ◽

Oxide Synthase

This study was designed to examine the effects of the antioxidant resveratrol on cardiac structure and function in pressure overload (PO)-induced cardiac hypertrophy. Male Sprague-Dawley rats were subjected to sham operation and the aortic banding procedure. A subgroup of sham control and aortic-banded rats were treated with resveratrol for 2 wk after surgery. Echocardiographic analysis of cardiac structure and function along with Western blot analysis of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and redox factor-1 (ref-1) were performed in all groups after 4 wk of surgery. Banded rats showed significantly increased left ventricle-to-body weight ratio. Echocardiographic analysis showed that the interventricular septal wall thickness and left ventricular posterior wall thickness at systole and diastole were significantly increased in banded rats. Also, a significant increase in isovolumic relaxation time was observed in banded rats. Measured eNOS, iNOS, and ref-1 protein levels were significantly reduced in banded rats. Resveratrol treatment prevented the above changes in cardiac structure, function, and protein expression in banded rats. Aortic banding after 4 wk resulted in concentric remodeling and impaired contractile function due to PO on the heart. The 2-wk treatment with resveratrol was found to abolish PO-induced cardiac hypertrophy. Resveratrol may therefore be beneficial against PO-induced cardiac hypertrophy found in clinical settings of hypertension and aortic valve stenosis.

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Abstract P094: Association of Body Mass Index (BMI) with Abnormalities of Cardiac Structure and Function: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.129.suppl_1.p094 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Natalie Bello ◽

Amil M Shah ◽

Angela B Santos ◽

Gabriela Querejeta Roca ◽

Orly Vardeny ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Left Ventricular ◽

Structure And Function ◽

Overweight And Obesity ◽

Cardiac Structure ◽

Significant Difference ◽

Cardiac Structure And Function ◽

And Function ◽

Rv Function

Aim: Obesity is a prevalent condition associated with a heightened risk of cardiovascular disease. We assessed the association between normal weight, overweight, and obesity defined by body mass index (BMI) and cardiac structure and function in a sample of 4,845 older adults, aged 66-90 years. Methods: We performed a cross-sectional analysis of ARIC cohort participants during visit 5 (2011-2013), excluding those with prevalent coronary heart disease, heart failure, or prior myocardial infarction, or race other than black or white. The sample was grouped into 3 categories: normal (n=1326, BMI <25 kg/m 2 ), overweight (n=1881, BMI 25-30 kg/m 2 ), and obese (n=1638, BMI ≥30 kg/m 2 ). Cardiac structure and function were assessed by 2D echocardiography by a core lab. Non-parametric trend, χ 2 tests, linear, and logistic regression were used for this analysis. A two-sided p-value <0.05 was considered significant. Results: Participants who were obese were younger, more likely to be black, and had higher rates of diabetes and hypertension than those who were overweight or had a normal BMI (table). Participants with obesity had larger biventricular cavity sizes, higher left ventricular (LV) mass index, more diastolic dysfunction, and more abnormal geometry (concentric/eccentric hypertrophy or concentric remodeling) than those who were overweight or normal (all p <0.0001). After adjustment (table), right ventricular (RV) function was lowest in obese participants, but there was no significant difference observed in LV ejection fraction. Conclusion: In ARIC, obesity is associated with increased LV remodeling, impaired diastolic function, and decreased RV function even after adjustment for significant covariates. The relationship of these findings to subsequent clinical events and whether they can be mitigated by weight loss or maintenance warrants further study.

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