Age and hypertrophy alter the contribution of sarcoplasmic reticulum and Na+/Ca2+ exchange to Ca2+ removal in rat left ventricular myocytes

Fowler, Mark R.; Naz, James R.; Graham, Mark; Orchard, Clive H.; Harrison, Simon

doi:10.1016/j.yjmcc.2006.12.003

Cited by 12 publications

(4 citation statements)

References 24 publications

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“…It has been proposed that a decline in SR proteins that participate in calcium removal plays a causative role (41), although other studies found no changes in the decay of calcium transient in aging, suggesting normal SERCA activity (39). Some studies describe changes in relaxation times compatible with reduced SERCA participation and compensatory increase in sarcolemmal Na + /Ca 2+ exchanger activity (42), while others advocate post-translational modifications, like increased oxidation of SERCA and phospholamban (43) or changes in the phosphorylation status of SR cycling proteins secondary to reduced CaM kinase II expression (44). To our knowledge, this is the first evidence indicating that depressed mitochondrial calcium uptake during ischaemia and reperfusion can be causally involved in the aggravation of cytosolic calcium overload of senescent cardiomyocytes.…”

Section: Mitochondrial Calcium Handling During Ischaemiareperfusionmentioning

confidence: 99%

Altered FoF1 ATP synthase and susceptibility to mitochondrial permeability transition pore during ischaemia and reperfusion in aging cardiomyocytes

Fernandez-Sanz¹,

Ruiz‐Meana²,

Castellano³

et al. 2015

Thromb Haemost

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Aging is a major determinant of the incidence and severity of ischaemic heart disease. Preclinical information suggests the existence of intrinsic cellular alterations that contribute to ischaemic susceptibility in senescent myocardium, by mechanisms not well established. We investigated the role of altered mitochondrial function in the adverse effect of aging. Isolated perfused hearts from old mice (> 20 months) displayed increased ischaemia-reperfusion injury as compared to hearts from adult mice (6 months) despite delayed onset of ischaemic rigor contracture. In cardiomyocytes from aging hearts there was a more rapid decline of mitochondrial membrane potential (Δψm) as compared to young ones, but ischaemic rigor shortening was also delayed. Transient recovery of Δψm observed during ischaemia, secondary to the reversal of mitochondrial FoF1 ATP synthase to ATPase mode, was markedly reduced in aging cardiomyocytes. Proteomic analysis demonstrated increased oxidation of different subunits of ATP synthase. Altered bionergetics in aging cells was associated with reduced mitochondrial calcium uptake and more severe cytosolic calcium overload during ischaemia-reperfusion. Despite attenuated ROS burst and mitochondrial calcium overload, mitochondrial permeability transition pore (mPTP) opening and cell death was increased in reperfused aged cells. In vitro studies demonstrated a significantly reduced calcium retention capacity in interfibrillar mitochondria from aging hearts. Our results identify altered FoF1 ATP synthase and increased sensitivity of mitochondria to undergo mPTP opening as important determinants of the reduced tolerance to ischaemia-reperfusion in aging hearts. Because ATP synthase has been proposed to conform mPTP, it is tempting to hypothesise that oxidation of ATP synthase underlie both phenomena.

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Section: Mitochondrial Calcium Handling During Ischaemiareperfusionmentioning

confidence: 99%

Altered FoF1 ATP synthase and susceptibility to mitochondrial permeability transition pore during ischaemia and reperfusion in aging cardiomyocytes

Fernandez-Sanz¹,

Ruiz‐Meana²,

Castellano³

et al. 2015

Thromb Haemost

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“…-Ca 2? exchanger, although both young and old animals exhibited cardiac hypertrophy [134]. Differences for changes in contractile parameters, action potential and Ca 2?…”

Section: Modification Of Age-induced Cardiac Dysfunction and Subcellumentioning

confidence: 96%

Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging

et al. 2011

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Although several risk factors including hypertension, cardiac hypertrophy, coronary artery disease, and diabetes are known to result in heart failure, elderly subjects are more susceptible to myocardial infarction and more likely to develop heart failure. This article is intended to discuss that cardiac dysfunction in hearts failing due to myocardial infarction and aging is associated with cardiac remodeling and defects in the subcellular organelles such as sarcolemma (SL), sarcoplasmic reticulum (SR), and myofibrils. Despite some differences in the pattern of heart failure due to myocardial infarction and aging with respect to their etiology and sequence of events, evidence has been presented to show that subcellular remodeling plays a critical role in the occurrence of intracellular Ca(2+)-overload and development of cardiac dysfunction in both types of failing heart. In particular, alterations in gene expression for SL and SR proteins induce Ca(2+)-handling abnormalities in cardiomyocytes, whereas those for myofibrillar proteins impair the interaction of Ca(2+) with myofibrils in hearts failing due to myocardial infarction and aging. In addition, different phosphorylation mechanisms, which regulate the activities of Ca(2+)-cycling proteins in SL and SR membranes as well as Ca(2+)-binding proteins in myofibrils, become defective in the failing heart. Accordingly, it is suggested that subcellular remodeling involving defects in Ca(2+)-handling and Ca(2+)-binding proteins as well as their regulatory mechanisms is intimately associated with cardiac remodeling and heart failure due to myocardial infarction and aging.

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“…Cardiac aging involves a number of senile changes associated with the cardiovascular system and other organs, which affect the structure and function of the cardiovascular system in a similar manner to hypertension, with symptoms including cardiac hypertrophy, reduced ventricular compliance and increased vascular stiffness (4–6). …”

Section: Introductionmentioning

confidence: 99%

Effects of long-term atorvastatin treatment on cardiac aging

Han

Liu

2013

Experimental and Therapeutic Medicine

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A number of studies have reported that atorvastatin (AVT) may have an important role in the delay of cardiac aging. However, the mechanism by which AVT affects cardiac aging has not been established. In this study, a series of experiments were performed to investigate the effects of AVT treatment on the cardiovascular system and the associated mechanism. Wistar rats were administered AVT or saline for 4 months. Age-related changes in the hearts were measured at the end of the experiment. The results showed that compared with young rats, the aged rats had significant changes indicative of myocardial aging, including increased blood lipid 1evelss, increased body weight, cardiac hypertrophy, larger myocardial cells, irregular muscle fibers, fewer deeply stained nuclei, smaller intercellular spaces, a larger number of apoptotic cells and increased levels of lipofuscin in myocardial tissue. However, long-term AVT treatment was able to significantly delay or even reverse these aging-related changes. In addition, these effects showed a certain dose-dependence. In general, long-term AVT treatment reduces blood lipids, inhibits cardiac hypertrophy, suppresses cardiomyocyte apoptosis and lowers the level of oxidative stress to protect the heart from aging.

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Age and hypertrophy alter the contribution of sarcoplasmic reticulum and Na+/Ca2+ exchange to Ca2+ removal in rat left ventricular myocytes

Cited by 12 publications

References 24 publications

Altered FoF1 ATP synthase and susceptibility to mitochondrial permeability transition pore during ischaemia and reperfusion in aging cardiomyocytes

Altered FoF1 ATP synthase and susceptibility to mitochondrial permeability transition pore during ischaemia and reperfusion in aging cardiomyocytes

Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging

Effects of long-term atorvastatin treatment on cardiac aging

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