Heart failure and the aging myocardium: Possible role of cardiac mitochondria

Odiet, Jeff A.; Wei, Jeanne Y.

doi:10.1007/bf00126378

Cited by 9 publications

(3 citation statements)

References 87 publications

(111 reference statements)

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“…In that sense, decreased fl uidity of the inner mitochondrial membrane negatively affects the activity of lipid-dependent enzymes and can contribute to an impairment of mitochondrial function. Changes in inner mitochondrial membrane composition, characterized by a decrease in unsaturated fatty acyls with a reciprocal increase in saturated acyls, have been proposed as a possible mechanism for heart failure in the aging myocardium ( 52 ). Defi ning a possible cause-effect relationship among the changes in cardiac fatty acid composition, mitochondrial membrane fl uidity, and cardiac function deserves further investigation.…”

Section: Discussionmentioning

confidence: 99%

Western diet changes cardiac acyl-CoA composition in obese rats: a potential role for hepatic lipogenesis

Harmancey¹,

Wilson²,

Wright³

et al. 2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org coronary artery disease ( 3,4 ). An imbalance between myocardial substrate uptake and fatty acid oxidative capacity of the heart is thought to induce lipotoxicity, namely, an accumulation of lipid byproducts that give rise to noxious intermediates in the cardiomyocytes. However, the exact mechanism for lipotoxicity is still not known. A consistent fi nding is that myocardial triglycerides are increased in hearts of obese or type 2 diabetic patients ( 5, 6 ), which is associated with impaired left-ventricular diastolic function ( 7 ).Genetically modifi ed rodent models have been used extensively to investigate the pathophysiology of "lipotoxic cardiomyopathy" ( 8 ). Increased lipid infl ux in the heart ( 9, 10 ), decreased mobilization of triacylglycerol reserves ( 11 ), or increased fatty acid metabolism (12)(13)(14) all are associated with metabolic alterations that mimic those of diabetes, including hypertrophy of the heart and contractile dysfunction. These animal studies have led to the identifi cation of the lipid molecules that are potential culprits for impaired cardiac function. Increased reliance of the heart on ␤ -oxidation of fatty acids leads to increased reactive oxygen species generation, which promotes lipid peroxidation and alters mitochondrial function ( 15,16 ). In addition, intracellular saturated acyl-CoA species, ceramide and diacylglycerol, are linked to changes in membrane composition, endoplasmic reticulum stress, altered lipid signaling, and ultimately, apoptosis ( 17,18 ). These lipid species may also impair insulin signaling through increased serine phosphorylation of the insulin receptor and insulin receptor substrate 1 and/or reduced serine phosphorylation of PKB/Akt ( 19,20 ).However, there is controversy over whether myocardial lipids contribute to contractile dysfunction and heart Abstract The "lipotoxic footprint" of cardiac maladaptation in diet-induced obesity is poorly defi ned. We investigated how manipulation of dietary lipid and carbohydrate infl uenced potential lipotoxic species in the failing heart. In Wistar rats, contractile dysfunction develops at 48 weeks on a high-fat/high-carbohydrate "Western" diet, but not on low-fat/high-carbohydrate or high-fat diets. Cardiac content of the lipotoxic candidates-diacylglycerol, ceramide, lipid peroxide, and long-chain acyl-CoA species-was measured at different time points by high-performance liquid chromatography and biochemical assays, as was lipogenic capacity in the heart and liver by qRT-PCR and radiometric assays. Changes in membranes fl uidity were also monitored using fl uorescence polarization. We report that Western feeding induced a 40% decrease in myocardial palmitoleoyl-CoA content and a similar decrease in the unsaturated-to-saturated fatty acid ratio. These changes were associated with impaired cardiac mitochondrial membrane fl uidity. At the same time, hepatic lipogenic capacity was increased in animals fed Western diet (+270% fatty acid elongase activity comp...

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Section: Discussionmentioning

confidence: 99%

Western diet changes cardiac acyl-CoA composition in obese rats: a potential role for hepatic lipogenesis

Harmancey¹,

Wilson²,

Wright³

et al. 2010

Journal of Lipid Research

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“…Dietary restriction has been shown in several animal models to prolong lifespan and reduce oxidative stress 56 . Altered mitochondrial function may also contribute to many observed age‐related changes 39,57 . One study in aging rats has shown that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril attenuated the age‐associated loss of the antioxidant defense enzyme superoxide dismutase in senescent cardiomyocytes, and there were greater numbers of mitochondria and less apoptosis of these cells 58 …”

Section: Functional Changesmentioning

confidence: 99%

Understanding the aging cardiovascular system

Wei

2004

Geriatrics Gerontology Int

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“…Impaired mitochondrial function, altered transcriptional regulation and changes in gene and protein expression are among the major factors that contribute to cellular senescence and adult aging (Khrapko et al, 1999; Nekhaeva et al, 2002; Odiet and Wei, 1996; Sun et al, 2016). Mitochondria are mobile intracellular organelles that exist in dynamic networks.…”

Section: Introductionmentioning

confidence: 99%

Does p49/STRAP, a SRF-binding protein (SRFBP1), modulate cardiac mitochondrial function in aging?

Zhang

Williams

Azhar

et al. 2016

Experimental Gerontology

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p49/STRAP (SRFBP1) is a transcriptional regulator that has been implicated in cardiac aging. p49/STRAP has a SRF binding domain and a BUD22 domain (which modulates cellular growth rate and cell size). We have observed that p49/STRAP alters the intracellular NAD/NADH ratio and induces protein deacetylation. Here we report that p49/STRAP overexpression caused the deacetylation of histone H4 on lysine 16 (H4K16) and suppressed the expression of PGC-1α as well as mitofusin-1 and mitofusin-2 at both the mRNA and protein levels. P49/STRAP also reduced mitochondrial size, mitochondrial membrane potential and the mitochondrial oxygen consumption rate. We noted that P49/STRAP expression was increased in the old versus young adult mouse hearts and also increased with advancing population doubling levels in cultured human umbilical vein endothelial cells (HUVECs). It is therefore very plausible that increased expression of p49/STRAP in late life may alter the status of histone acetylation and impact mitochondrial dynamics and thereby reduce mitochondrial function and cardiac performance during mammalian senescence.

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Heart failure and the aging myocardium: Possible role of cardiac mitochondria

Cited by 9 publications

References 87 publications

Western diet changes cardiac acyl-CoA composition in obese rats: a potential role for hepatic lipogenesis

Western diet changes cardiac acyl-CoA composition in obese rats: a potential role for hepatic lipogenesis

Understanding the aging cardiovascular system

Does p49/STRAP, a SRF-binding protein (SRFBP1), modulate cardiac mitochondrial function in aging?

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