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Hugo E Verdejo, Andrea Del Campo,
Rodrigo Troncoso,
Tomás Gutierrez,
Barbra Toro,
Clara Quiroga,
Zully Pedrozo,
Juan Pablo Munoz,
Lorena Garcia,
Pablo F Castro,
Sergio Lavandero
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ABSTRACT: The process of muscle remodeling lies at the core of most cardiovascular diseases. Cardiac adaptation to pressure or volume overload is associated with a complex molecular change in cardiomyocytes which leads to anatomic remodeling of the heart muscle. Although adaptive at its beginnings, the sustained cardiac hypertrophic remodeling almost unavoidably ends in progressive muscle dysfunction, heart failure and ultimately death. One of the features of cardiac remodeling is a progressive impairment in mitochondrial function. The heart has the highest oxygen uptake in the human body and accordingly it has a large number of mitochondria, which form a complex network under constant remodeling in order to sustain the high metabolic rate of cardiac cells and serve as Ca(2+) buffers acting together with the endoplasmic reticulum (ER). However, this high dependence on mitochondrial metabolism has its costs: when oxygen supply is threatened, high leak of electrons from the electron transport chain leads to oxidative stress and mitochondrial failure. These three aspects of mitochondrial function (Reactive oxygen species signaling, Ca(2+) handling and mitochondrial dynamics) are critical for normal muscle homeostasis. In this article, we will review the latest evidence linking mitochondrial morphology and function with the process of myocardial remodeling and cardiovascular disease.
Current Hypertension Reports 09/2012; · 2.50 Impact Factor
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Rodrigo Troncoso,
Jose Miguel Vicencio,
Valentina Parra,
Andriy Nemchenko,
Yuki Kawashima, Andrea Del Campo,
Barbra Toro,
Pavan K Battiprolu,
Pablo Aranguiz,
Mario Chiong,
Shoshana Yakar,
Thomas G Gillette,
Joseph A Hill,
Evan Dale Abel,
Derek Leroith,
Sergio Lavandero
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ABSTRACT: Insulin-like growth factor 1 (IGF-1) is known to exert cardioprotective actions. However, it remains unknown if autophagy, a major adaptive response to nutritional stress, contributes to IGF-1-mediated cardioprotection.
We subjected cultured neonatal rat cardiomyocytes, as well as live mice, to nutritional stress and assessed cell death and autophagic rates. Nutritional stress induced by serum/glucose deprivation strongly induced autophagy and cell death, and both responses were inhibited by IGF-1. The Akt/mammalian target of rapamycin (mTOR) pathway mediated the effects of IGF-1 upon autophagy. Importantly, starvation also decreased intracellular ATP levels and oxygen consumption leading to AMP-activated protein kinase (AMPK) activation; IGF-1 increased mitochondrial Ca(2+) uptake and mitochondrial respiration in nutrient-starved cells. IGF-1 also rescued ATP levels, reduced AMPK phosphorylation and increased p70(S6K) phosphorylation, which indicates that in addition to Akt/mTOR, IGF-1 inhibits autophagy by the AMPK/mTOR axis. In mice harbouring a liver-specific igf1 deletion, which dramatically reduces IGF-1 plasma levels, AMPK activity and autophagy were increased, and significant heart weight loss was observed in comparison with wild-type starved animals, revealing the importance of IGF-1 in maintaining cardiac adaptability to nutritional insults in vivo.
Our data support the cardioprotective actions of IGF-1, which, by rescuing the mitochondrial metabolism and the energetic state of cells, reduces cell death and controls the potentially harmful autophagic response to nutritional challenges. IGF-1, therefore, may prove beneficial to mitigate damage induced by excessive nutrient-related stress, including ischaemic disease in multiple tissues.
Cardiovascular research 12/2011; 93(2):320-9. · 5.80 Impact Factor
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Jovan Kuzmicic, Andrea Del Campo,
Camila López-Crisosto,
Pablo E Morales,
Christian Pennanen,
Roberto Bravo-Sagua,
Jonathan Hechenleitner,
Ramiro Zepeda,
Pablo F Castro,
Hugo E Verdejo,
Valentina Parra,
Mario Chiong,
Sergio Lavandero
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ABSTRACT: Mitochondria are dynamic organelles able to vary their morphology between elongated interconnected mitochondrial networks and fragmented disconnected arrays, through events of mitochondrial fusion and fission, respectively. These events allow the transmission of signaling messengers and exchange of metabolites within the cell. They have also been implicated in a variety of biological processes including embryonic development, metabolism, apoptosis, and autophagy. Although the majority of these studies have been confined to noncardiac cells, emerging evidence suggests that changes in mitochondrial morphology could participate in cardiac development, the response to ischemia-reperfusion injury, heart failure, and diabetes mellitus. In this article, we review how the mitochondrial dynamics are altered in different cardiac pathologies, with special emphasis on heart failure, and how this knowledge may provide new therapeutic targets for treating cardiovascular diseases.
Revista Espa de Cardiologia 08/2011; 64(10):916-23. · 2.53 Impact Factor
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ABSTRACT: Mitochondria are highly dynamic organelles, capable of undergoing constant fission and fusion events, forming networks. These dynamic events allow the transmission of chemical and physical messengers and the exchange of metabolites within the cell. In this article we review the signaling mechanisms controlling mitochondrial fission and fusion, and its relationship with cell bioenergetics, especially in the heart. Furthermore we also discuss how defects in mitochondrial dynamics might be involved in the pathogenesis of metabolic cardiac diseases.
Journal of Bioenergetics 01/2011; 43(1):47-51. · 2.81 Impact Factor
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Hugo Verdejo,
Juan Roldan,
Lorena Garcia, Andrea Del Campo,
Elia Becerra,
Mario Chiong,
Rosemarie Mellado,
Amalia Garcia,
Ricardo Zalaquett,
Sandra Braun,
Bernardita Garayar,
Sergio Gonzalez,
Sergio Lavandero,
Ramon Corbalan
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ABSTRACT: Post-operative atrial fibrillation occurs in 30% of patients after on-pump heart surgery and is associated to elevated inflammatory markers. We have evaluated if the systemic biomarkers of inflammation and endothelial damage, vascular cell adhesion molecule-1 (VCAM-1) and soluble thrombomodulin may help in identifying patients prone to development of post-operative atrial fibrillation.
One hundred and forty-four patients in sinus rhythm submitted to elective coronary artery bypass surgery. Systemic inflammatory, oxidative stress and endothelial damage markers were measured at baseline and 72 h after surgery. During the procedure, a sample of the right atrial appendage was obtained for histochemistry. Electrocardiogram was monitored for 72 h after surgery for event adjudication.
22% of the patients developed post-operative atrial fibrillation. Baseline systemic inflammatory markers did not differ between patients with or without post-operative atrial fibrillation. However, baseline plasma VCAM-1 and thrombomodulin levels were significantly higher in patients who developed post-operative atrial fibrillation. After adjustment for age, gender, comorbidities and concurrent medication, circulating VCAM-1 remained as an independent predictor for post-operative atrial fibrillation development. No association was observed between systemic plasma VCAM-1 and VCAM-1 tissue expression in the right atrial appendage.
In patients undergoing coronary artery bypass surgery, elevated VCAM-1 levels predict a higher risk for post-operative atrial fibrillation. Plasma VCAM-1 elevation is not related to its expression in the right atria, suggesting that systemic endothelial damage rather than local changes pre-exist in patients who develop the arrhythmia.
International journal of cardiology 05/2010; 150(3):270-6. · 7.08 Impact Factor
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Rodrigo Troncoso,
Francisco Moraga,
Mario Chiong,
Juan Roldán,
Roberto Bravo,
Rodrigo Valenzuela,
Guillermo Díaz-Araya, Andrea del Campo,
Carlos Sanhueza,
Andrea Rodriguez,
José Luis Vukasovic,
Rosemarie Mellado,
Douglas Greig,
Pablo F Castro,
Sergio Lavandero
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ABSTRACT: We investigated the clinical response of chronic heart failure patients with beta(2)-adrenergic receptor Gln(27)-->Glu polymorphism treated for 6 months with carvedilol, a alpha/beta-antagonist with antioxidant properties. The 6-min. walk test, the left ventricular ejection fraction, heart rate, plasma norepinephrine and malondialdehyde, a stress oxidative marker, concentrations were evaluated at baseline and after treatment for 6 months with carvedilol in 33 stable chronic heart failure patients with the Gln(27)-->Glubeta(2)-adrenergic receptor polymorphism. Carvedilol significantly increased the left ventricular ejection fraction, while decreasing the heart rate and malondialdehyde plasma concentrations in chronic heart failure patients with the Glu(27)beta(2)-adrenergic receptor allele. There were however, no significant changes in patients with the Gln(27)beta(2)-adrenergic receptor variant.
Basic & Clinical Pharmacology & Toxicology 05/2009; 104(5):374-8. · 2.18 Impact Factor
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Rodrigo Troncoso,
Francisco Moraga,
Mario Chiong,
Juan Roldán,
Roberto Bravo,
Rodrigo Valenzuela,
Guillermo Díaz-Araya, Andrea Del Campo,
Carlos Sanhueza,
Andrea Rodriguez,
José Luis Vukasovic,
Rosemarie Mellado,
Douglas Greig,
Pablo F. Castro,
Sergio Lavandero
[show abstract]
[hide abstract]
ABSTRACT: We investigated the clinical response of chronic heart failure patients with β2-adrenergic receptor Gln27→Glu polymorphism treated for 6 months with carvedilol, a /β-antagonist with antioxidant properties. The 6-min. walk test, the left ventricular ejection fraction, heart rate, plasma norepinephrine and malondialdehyde, a stress oxidative marker, concentrations were evaluated at baseline and after treatment for 6 months with carvedilol in 33 stable chronic heart failure patients with the Gln27→Gluβ2-adrenergic receptor polymorphism. Carvedilol significantly increased the left ventricular ejection fraction, while decreasing the heart rate and malondialdehyde plasma concentrations in chronic heart failure patients with the Glu27β2-adrenergic receptor allele. There were however, no significant changes in patients with the Gln27β2-adrenergic receptor variant.
Basic & Clinical Pharmacology & Toxicology 01/2009; 104(5):374 - 378. · 2.18 Impact Factor
