Possible Involvement of Mitochondrial Energy-Producing Ability in the Development of Right Ventricular Failure in Monocrotaline-Induced Pulmonary Hypertensive Rats

Daicho, Takuya; Yagi, T.; Abe, Yohei; Ohara, Meiko; Marunouchi, Tetsuro; Takeo, Satoshi; Tanonaka, Kouichi

doi:10.1254/jphs.08322fp

Cited by 36 publications

(41 citation statements)

References 27 publications

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“…83 In contrast, in monocrotaline-induced RVH, decreases in both phosphocreatine and ATP levels were observed. 82 Right ventricular dysfunction is associated with increased glycolysis Takeyama et al 85 observed that glucose uptake was increased in the right ventricle of conscious rats 4 weeks after pulmonary constriction (using 14 C-2 deoxyglucose [2DG]). There was no difference in 14 C β-methylheptadecanoic acid (BMHDA) accumulation, suggesting no differences in fatty acid uptake between sham and hypertrophied right ventricles.…”

Section: Cardiac Metabolism In Right Heart Failurementioning

confidence: 99%

Cardiac Energy Metabolic Alterations in Pressure Overload–Induced Left and Right Heart Failure (2013 Grover Conference Series)

Sankaralingam

Lopaschuk

2015

Pulm. circ.

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Pressure overload of the heart, such as seen with pulmonary hypertension and/or systemic hypertension, can result in cardiac hypertrophy and the eventual development of heart failure. The development of hypertrophy and heart failure is accompanied by numerous molecular changes in the heart, including alterations in cardiac energy metabolism. Under normal conditions, the high energy (adenosine triphosphate [ATP]) demands of the heart are primarily provided by the mitochondrial oxidation of fatty acids, carbohydrates (glucose and lactate), and ketones. In contrast, the hypertrophied failing heart is energy deficient because of its inability to produce adequate amounts of ATP. This can be attributed to a reduction in mitochondrial oxidative metabolism, with the heart becoming more reliant on glycolysis as a source of ATP production. If glycolysis is uncoupled from glucose oxidation, a decrease in cardiac efficiency can occur, which can contribute to the severity of heart failure due to pressure-overload hypertrophy. These metabolic changes are accompanied by alterations in the enzymes that are involved in the regulation of fatty acid and carbohydrate metabolism. It is now becoming clear that optimizing both energy production and the source of energy production are potential targets for pharmacological intervention aimed at improving cardiac function in the hypertrophied failing heart. In this review, we will focus on what alterations in energy metabolism occur in pressure overload induced left and right heart failure. We will also discuss potential targets and pharmacological approaches that can be used to treat heart failure occurring secondary to pulmonary hypertension and/or systemic hypertension.

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Section: Cardiac Metabolism In Right Heart Failurementioning

confidence: 99%

Cardiac Energy Metabolic Alterations in Pressure Overload–Induced Left and Right Heart Failure (2013 Grover Conference Series)

Sankaralingam

Lopaschuk

2015

Pulm. circ.

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“…Impairment of oxygen consumption and energy production was shown to correlate with exacerbation of heart function in pulmonary arterial hypertension (PAH)-induced right ventricular (RV) failure [24]. A more detailed examination of energetic dysfunction in a pressureoverloaded rat heart suggested that the transition into heart failure correlates closely with decreases in mitochondrial respiratory capacity [10•].…”

Section: Mitochondrial Dysfunction and Hypertensionmentioning

confidence: 99%

Mitochondrial Dysfunction and Oxidative Damage to Sarcomeric Proteins

Bayeva

Ardehali

2010

Curr Hypertens Rep

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Hypertension is an important risk factor for the development of heart failure. Increased production of reactive oxygen species (ROS) contributes to cardiac dysfunction by activating numerous pro-hypertrophic signaling cascades and damaging the mitochondria, thus setting off a vicious cycle of ROS generation. The way in which oxidative stress leads to exacerbation of systolic and diastolic dysfunction is still unclear, however. In skeletal muscle and ischemic myocardium, increased ROS production causes preferential oxidation of myofibrillar proteins and provides a mechanistic link between oxidative damage and impaired contractility through disruption of actin-myosin interactions, enzymatic functions, calcium sensitivity, and efficiency of cross-bridge cycling. In this review, we summarize recent findings in the fields of heart failure and sarcomere biology and speculate that oxidative damage to myofibrils may contribute to the development of heart failure.

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“…Although it is acutely toxic to mitochondria, MCT has no longstanding actions after a single administration and mitochondrial disturbances only develop with PH progression (20).…”

Section: Discussionmentioning

confidence: 99%

A Western-Type Diet Attenuates Pulmonary Hypertension with Heart Failure and Cardiac Cachexia in Rats

Lourenço

Vasques‐Nóvoa

Fontoura

et al. 2011

The Journal of Nutrition

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Western-type diets (WD) constitute risk factors for disease but may have distinct effects in heart failure (HF) with cardiac cachexia (CC). We evaluated hemodynamic, metabolic, and inflammatory effects of short-term WD intake in pulmonary hypertension (PH) with CC. Male Wistar rats randomly received 60 mg · kg(-1) monocrotaline (M) or vehicle (C) and consumed either a 5.4-kcal · g(-1) WD (35% animal fat, 35% simple carbohydrate, 20% protein, 0.4% Na(+)) or a 2.9-kcal · g(-1) (3% vegetable fat, 60% complex carbohydrate, 16% protein, 0.25% Na(+)) normal diet (ND) for 5 wk. Mortality, energy intake, body weight (BW), metabolism, hemodynamics, histology, apoptosis, gene expression, transcription factors, and plasma cytokines were evaluated. Compared with the C-ND group, the M-ND group had PH, HF, and mortality that were significantly attenuated in M-WD. The extent of myocardial remodeling and apoptosis was higher in M-ND than in C-ND but lower in M-WD than in M-ND, while conversely, energy intake, BW, cholesterol, and TG plasma concentrations were lower in M-ND than in C-ND but higher in M-WD than in M-ND. M-ND had increased myocardial NF-κB transcription factor activity, endothelin-1, and cytokine overexpression and higher circulating cytokine concentrations than C-ND, which were lower in M-WD than in M-ND. PPARα activity, however, was lower in M-ND, but not in M-WD, compared with the respective C groups. WD attenuated PH and CC, ameliorating survival, myocardial function, metabolism, and inflammation, through transcription factor modulation, suggesting a beneficial role in CC.

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Possible Involvement of Mitochondrial Energy-Producing Ability in the Development of Right Ventricular Failure in Monocrotaline-Induced Pulmonary Hypertensive Rats

Cited by 36 publications

References 27 publications

Cardiac Energy Metabolic Alterations in Pressure Overload–Induced Left and Right Heart Failure (2013 Grover Conference Series)

Cardiac Energy Metabolic Alterations in Pressure Overload–Induced Left and Right Heart Failure (2013 Grover Conference Series)

Mitochondrial Dysfunction and Oxidative Damage to Sarcomeric Proteins

A Western-Type Diet Attenuates Pulmonary Hypertension with Heart Failure and Cardiac Cachexia in Rats

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