scholarly journals A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload

2008 ◽  
Vol 295 (6) ◽  
pp. H2495-H2502 ◽  
Author(s):  
Michael J. Raher ◽  
Helene B. Thibault ◽  
Emmanuel S. Buys ◽  
Darshini Kuruppu ◽  
Nobuyuki Shimizu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Myocardial Perfusion ◽  
Short Duration ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Systemic Hypertension ◽  
High Fat ◽  
Lv Remodeling ◽  
And Function ◽  
The Impact

Insulin resistance is an increasingly prevalent condition in humans that frequently clusters with disorders characterized by left ventricular (LV) pressure overload, such as systemic hypertension. To investigate the impact of insulin resistance on LV remodeling and functional response to pressure overload, C57BL6 male mice were fed a high-fat (HFD) or a standard diet (SD) for 9 days and then underwent transverse aortic constriction (TAC). LV size and function were assessed in SD- and HFD-fed mice using serial echocardiography before and 7, 21, and 28 days after TAC. Serial echocardiography was also performed on nonoperated SD- and HFD-fed mice over a period of 6 wk. LV perfusion was assessed before and 7 and 28 days after TAC. Nine days of HFD induced systemic and myocardial insulin resistance (assessed by myocardial 18F-fluorodeoxyglucose uptake), and myocardial perfusion response to acetylcholine was impaired. High-fat feeding for 28 days did not change LV size and function in nonbanded mice; however, TAC induced greater hypertrophy, more marked LV systolic and diastolic dysfunction, and decreased survival in HFD-fed compared with SD-fed mice. Compared with SD-fed mice, myocardial perfusion reserve was decreased 7 days after TAC, and capillary density was decreased 28 days after TAC in HFD-fed mice. A short duration of HFD induces insulin resistance in mice. These metabolic changes are accompanied by increased LV remodeling and dysfunction after TAC, highlighting the impact of insulin resistance in the development of pressure-overload-induced heart failure.

scholarly journals Nitric oxide synthase 3 deficiency limits adverse ventricular remodeling after pressure overload in insulin resistance

2011 ◽  
Vol 301 (5) ◽  
pp. H2093-H2101 ◽  
Author(s):  
Baptiste Kurtz ◽  
Helene B. Thibault ◽  
Michael J. Raher ◽  
John R. Popovich ◽  
Sharon Cawley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Insulin Resistance ◽  
Mitochondrial Respiration ◽  
Pressure Overload ◽  
Lv Remodeling ◽  
Stress Levels ◽  
Nitric Oxide Synthase 3 ◽  
And Function ◽  
Oxide Synthase

Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3−/−) mice were fed either a standard diet (SD) or a high-fat diet (HFD) to induce IR. After 9 days of diet, mice underwent transverse aortic constriction (TAC). LV structure and function were assessed serially using echocardiography. Cardiomyocytes were isolated, and levels of oxidative stress were evaluated using 2′,7′-dichlorodihydrofluorescein diacetate. Cardiac mitochondria were isolated, and mitochondrial respiration and ATP production were measured. TAC induced LV remodeling and dysfunction in all mice. The TAC-induced decrease in LV function was greater in SD-fed NOS3−/− mice than in SD-fed WT mice. In contrast, HFD-fed NOS3−/− developed less LV remodeling and dysfunction and had better survival than did HFD-fed WT mice. Seven days after TAC, oxidative stress levels were lower in cardiomyocytes from HFD-fed NOS3−/− than in those from HFD-fed WT. Nω-nitro-l-arginine methyl ester and mitochondrial inhibitors (rotenone and 2-thenoyltrifluoroacetone) decreased oxidative stress levels in cardiomyocytes from HFD-fed WT mice. Mitochondrial respiration was altered in NOS3−/− mice but did not worsen after HFD and TAC. In contrast with its protective role in SD, NOS3 increases LV adverse remodeling after pressure overload in HFD-fed, insulin resistant mice. Interactions between NOS3 and mitochondria may be responsible for increased oxidative stress levels in HFD-fed WT mice hearts.

Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency

2004 ◽  
Vol 286 (3) ◽  
pp. H1070-H1075 ◽  
Author(s):  
Fumito Ichinose ◽  
Kenneth D. Bloch ◽  
Justina C. Wu ◽  
Ryuji Hataishi ◽  
H. Thomas Aretz ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Maximum Rate ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Mouse Strains ◽  
Term Administration ◽  
And Function ◽  
The Impact ◽  
Fractional Shortening

To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling induced by chronic pressure overload, the impact of transverse aortic constriction (TAC) on LV structure and function was compared in wild-type (WT) and NOS3-deficient (NOS3–/–) mice. Before TAC, LV wall thickness, mass, and fractional shortening were similar in the two mouse strains. Twenty-eight days after TAC, both WT and NOS3–/– mice had increased LV wall thickness and mass as well as decreased fractional shortening. Although the pressure gradient across the TAC was similar in both strains of mice 28 days after TAC, LV mass and posterior wall thickness were greater in NOS3–/– than in WT mice, whereas fractional shortening and the maximum rate of developed LV pressure were less. Diastolic function, as measured by the time constant of isovolumic relaxation and the maximum rate of LV pressure decay, was impaired to a greater extent in NOS3–/– than in WT mice. The degree of myocyte hypertrophy and LV fibrosis was greater in NOS3–/– than in WT mice at 28 days after TAC. Mortality was greater in NOS3–/– than in WT mice 28 days after TAC. Long-term administration of hydralazine normalized the blood pressure and prevented the LV dilation in NOS3–/– mice but did not prevent the LV hypertrophy, dysfunction, and fibrosis associated with NOS3 deficiency after TAC. These results suggest that the absence of NOS3 augments LV dysfunction and remodeling in a murine model of chronic pressure overload.

Impact of mitral regurgitation on left ventricular anatomic and molecular remodeling and systolic function: implication for outcome

2009 ◽  
Vol 296 (6) ◽  
pp. H1727-H1732 ◽  
Author(s):  
Min Pu ◽  
Zhaohui Gao ◽  
Xueqian Zhang ◽  
Duanping Liao ◽  
Daniel K. Pu ◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Time Course ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Sham Operation ◽  
Proportional Hazard ◽  
Long Term Outcome ◽  
Lv Remodeling ◽  
And Function ◽  
The Impact

The aim of the study was to assess the impact of mitral regurgitation (MR) on left ventricular (LV) anatomic and molecular remodeling and function and to determine whether early LV remodeling and function predict long-term outcome in experimental organic MR. A new rodent model of chronic MR was created. Twenty-eight rats had surgically induced MR, twelve rats had a sham operation, and twelve rats had no operation. LV diameters, volume, and mass and LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were assessed using echocardiography in the early stage of MR (6 and 12 wk after induction of MR). LV hemodynamics was assessed invasively. Cardiac α- and β-myosin heavy chains and sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) were measured to assess molecular remodeling and contractility. Cox's proportional hazard ratios (HR) were used to identify outcome predictors. Early LV dilation was demonstrated in rats with MR when LVEF and LVFS were still normal. LV remodeling was associated with an increase in LV end-diastolic pressure and decrease in maximal change in pressure over time. Shifting of α- to β-myosin and reduced SERCA2 were observed in rats with MR. Cox's proportional hazard analysis showed that LV end-diastolic diameters (HR, 1.2–2.4; P = 0.007) and LV end-diastolic volume (HR, 1.1–1.4; P = 0.005) at 6 wk and LV mass index (HR, 1.1–2.0; P = 0.004) at 12 wk after induction of MR were significantly associated with 1-yr mortality. However, LVEF (HR, 0.7–6.8 for the 6 wk, P > 0.05; and HR, 0.4–3.2 for the 12 wk, P > 0.05) and LVFS (HR, 0.4–1.4 for the 6 wk; and 0.4–3.1 for the 12 wk, P > 0.05) did not predict late death. Chronic MR leads to LV anatomic and cellular remodeling and impaired contractility. The time course of LV remodeling and function changes in the rat model of MR is similar to humans. Prediction of outcome may be achieved by assessments of early LV remodeling.

Sex-Related Differences in the Impact of Systemic Hypertension on Left Ventricular Remodeling in Patients with Hypertrophic Obstructive Cardiomyopathy

Cardiology ◽  
2020 ◽  
Vol 145 (4) ◽  
pp. 203-214 ◽  
Author(s):  
Yue Zhou ◽  
Miao Yu ◽  
Jiansong Yuan ◽  
Fenghuan Hu ◽  
Shengwen Liu ◽  
...  
Keyword(s):  
Troponin I ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Hypertrophic Obstructive Cardiomyopathy ◽  
Left Ventricular ◽  
Systemic Hypertension ◽  
Logistic Analysis ◽  
Lv Remodeling ◽  
Sudden Cardiac Death Risk ◽  
The Impact

Background: The clinical condition of hypertrophic obstructive cardiomyopathy (HOCM) and concomitant systemic hypertension is growing more and more prevalent, and it brings about a challenging diagnostic and therapeutic dilemma. However, whether systemic hypertension has an impact on HOCM, and whether sex-related differences exist in this impact, remains unclear. Methods: A total of 453 HOCM patients (age 48.7 ± 12.8 years, 252 [55.6%] males) were recruited in this study. There were 150 patients (33.1%, 81 males and 69 females) with a history of controlled systemic hypertension. Cardiac magnetic resonance (CMR) imaging was performed in all patients. Left ventricular (LV) remodeling index (LVRI) was determined by CMR. LVRI >1.3 g/mL was defined as pathological LV remodeling. Results: Men had significantly greater LVRI (1.40 ± 0.54 vs. 1.15 ± 0.38 g/mL, p < 0.001) and LVRI >1.3 g/mL (p = 0.002), compared with women. The incidence of syncope and 5-year sudden cardiac death risk score were significantly lower in HOCM with hypertension than those without hypertension. LVRI (p = 0.003) and LVRI >1.3 g/mL (p = 0.007) were significantly smaller in males with hypertension, but not in females with hypertension. However, log cardiac troponin I and log N-terminal pro-B-type natriuretic peptide were positively correlated with LVRI in men and women. On multivariable logistic analysis, hypertension (OR 0.172, 95% CI 0.056–0.528, p = 0.002) remained an independent determinant of pathological LV remodeling in males, whereas not in females. Conclusions: There were significant sex differences in the impact of systemic hypertension on LV remodeling in patients with HOCM. Controlled systemic hypertension may contribute to improving LV remodeling in male patients with HOCM, but not in females.

Cardiomyocyte-restricted restoration of nitric oxide synthase 3 attenuates left ventricular remodeling after chronic pressure overload

2007 ◽  
Vol 293 (1) ◽  
pp. H620-H627 ◽  
Author(s):  
Emmanuel S. Buys ◽  
Michael J. Raher ◽  
Sarah L. Blake ◽  
Tomas G. Neilan ◽  
Amanda R. Graveline ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Ventricular Remodeling ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Lv Remodeling ◽  
And Function ◽  
Oxide Synthase ◽  
Deficient Mice

Although nitric oxide synthase (NOS)3 is implicated as an important modulator of left ventricular (LV) remodeling, its role in the cardiac response to chronic pressure overload is controversial. We examined whether selective restoration of NOS3 to the hearts of NOS3-deficient mice would modulate the LV remodeling response to transverse aortic constriction (TAC). LV structure and function were compared at baseline and after TAC in NOS3-deficient (NOS3−/−) mice and NOS3−/− mice carrying a transgene directing NOS3 expression specifically in cardiomyocytes (NOS3−/−TG mice). At baseline, echocardiographic assessment of LV dimensions and function, invasive hemodynamic measurements, LV mass, and myocyte width did not differ between the two genotypes. Four weeks after TAC, echocardiographic and hemodynamic indexes of LV systolic function indicated that contractile performance was better preserved in NOS3−/−TG mice than in NOS3−/− mice. Echocardiographic LV wall thickness and cardiomyocyte width were greater in NOS3−/− mice than in NOS3−/−TG mice. TAC-induced cardiac fibrosis did not differ between these genotypes. TAC increased cardiac superoxide generation in NOS3−/−TG but not NOS3−/− mice. The ratio of NOS3 dimers to monomers did not differ before and after TAC in NOS3−/−TG mice. Restoration of NOS3 to the heart of NOS3-deficient mice attenuates LV hypertrophy and dysfunction after TAC, suggesting that NOS3 protects against the adverse LV remodeling induced by prolonged pressure overload.

scholarly journals Lack of Contribution of p66shc to Pressure Overload-Induced Right Heart Hypertrophy

2020 ◽  
Vol 21 (24) ◽  
pp. 9339
Author(s):  
Christine Hirschhäuser ◽  
Akylbek Sydykov ◽  
Annemarie Wolf ◽  
Azadeh Esfandiary ◽  
Julia Bornbaum ◽  
...  
Keyword(s):  
Pressure Overload ◽  
Left Ventricular ◽  
Sham Operation ◽  
Ros Production ◽  
Mitochondrial Ros ◽  
Ros Formation ◽  
Pulmonary Arterial ◽  
Genetic Deletion ◽  
And Function ◽  
The Impact

The leading cause of death in pulmonary arterial hypertension (PAH) is right ventricular (RV) failure (RVF). Reactive oxygen species (ROS) have been suggested to play a role in the development of RV hypertrophy (RVH) and the transition to RVF. The hydrogen peroxide-generating protein p66shc has been associated with left ventricular (LV) hypertrophy but its role in RVH is unclear. The purpose of this study was to determine whether genetic deletion of p66shc affects the development and/or progression of RVH and RVF in the pulmonary artery banding (PAB) model of RV pressure overload. The impact of p66shc on mitochondrial ROS formation, RV cardiomyocyte function, as well as on RV morphology and function were studied three weeks after PAB or sham operation. PAB in wild type mice did not affect mitochondrial ROS production or RV cardiomyocyte function, but induced RVH and impaired cardiac function. Genetic deletion of p66shc did also not alter basal mitochondrial ROS production or RV cardiomyocyte function, but impaired RV cardiomyocyte shortening was observed following PAB. The development of RVH and RVF following PAB was not affected by p66shc deletion. Thus, our data suggest that p66shc-derived ROS are not involved in the development and progression of RVH or RVF in PAH.

scholarly journals Inheritable testicular metabolic memory of high-fat diet causes transgenerational sperm defects in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luís Crisóstomo ◽  
Ivana Jarak ◽  
Luís P. Rato ◽  
João F. Raposo ◽  
Rachel L. Batterham ◽  
...  
Keyword(s):  
Sperm Quality ◽  
Feeding Habits ◽  
Reproductive Function ◽  
Principal Component ◽  
Testicular Tissue ◽  
Sperm Parameters ◽  
Metabolic Memory ◽  
High Fat ◽  
And Function ◽  
The Impact

AbstractThe consumption of energy-dense diets has contributed to an increase in the prevalence of obesity and its comorbidities worldwide. The adoption of unhealthy feeding habits often occurs at early age, prompting the early onset of metabolic disease with unknown consequences for reproductive function later in life. Recently, evidence has emerged regarding the intergenerational and transgenerational effects of high-fat diets (HFD) on sperm parameters and testicular metabolism. Hereby, we study the impact of high-fat feeding male mice (F0) on the testicular metabolome and function of their sons (F1) and grandsons (F2). Testicular content of metabolites related to insulin resistance, cell membrane remodeling, nutritional support and antioxidative stress (leucine, acetate, glycine, glutamine, inosine) were altered in sons and grandsons of mice fed with HFD, comparing to descendants of chow-fed mice. Sperm counts were lower in the grandsons of mice fed with HFD, even if transient. Sperm quality was correlated to testicular metabolite content in all generations. Principal Component Analysis of sperm parameters and testicular metabolites revealed an HFD-related phenotype, especially in the diet-challenged generation and their grandsons. Ancestral HFD, even if transient, causes transgenerational “inherited metabolic memory” in the testicular tissue, characterized by changes in testicular metabolome and function.

Abstract 18922: Radiofrequency Catheter Ablation Reduces Diffuse Myocardial Fibrosis in Atrial Fibrillation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Promporn Suksaranjit ◽  
Brent D Wilson ◽  
Christopher J McGann ◽  
Eugene G Kholmovski ◽  
Imran Haider ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Myocardial Fibrosis ◽  
Radiofrequency Catheter Ablation ◽  
T1 Mapping ◽  
Left Ventricular ◽  
Diffuse Myocardial Fibrosis ◽  
T1 Relaxation ◽  
Lv Remodeling ◽  
The Impact

Introduction: Atrial fibrillation (AF) is associated with diffuse myocardial fibrosis as quantified by cardiac magnetic resonance (CMR) using T1 mapping methods. Radiofrequency catheter ablation (RFCA) is evolving, and the role in rhythm control may be ideal for reversing left ventricular (LV) remodeling. Hypothesis: We aimed to study the impact of RFCA on diffuse myocardial fibrosis in AF patients. Methods: We retrospectively collected data from consecutive AF patients who underwent RFCA with modified Look-Locker Inversion recovery T1 mapping sequences on pre/post procedural CMR at 3.0-Tesla. Precontrast T1 relaxation time of the mid-LV short-axis view was used as an index of diffuse LV fibrosis. Primary outcome was the change in diffuse LV fibrosis after RFCA. Results: A total of 11 patients (mean age 67 years, 72% male, 67% paroxysmal AF) were enrolled. Median AF duration was 24.6 months [Interquartile range (IQR): 13.3-45.3)] and median CHA2DS2-VASc was 2 [IQR: 1-3]. Post RFCA CMR was obtained 99.5±18.1 days after the RFCA procedure. Mean precontrast T1 time was significantly lower after RFCA (1182ms vs 1158ms; p=0.0157). Conclusions: Based on our preliminary results, RFCA in AF reduces diffuse myocardial fibrosis and may play a role in reverse LV remodeling.

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