Altered phospholipid metabolism in pressure-overload hypertrophied hearts

Reibel, Diane K.; O’Rourke, Brian; Foster, Karen; Hutchinson, Howard G.; Uboh, Cornelius E.; Kent, Robert L.

doi:10.1152/ajpheart.1986.250.1.h1

Cited by 47 publications

(37 citation statements)

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“…The mass of the other major phospholipids, including PA, were not significantly different between groups. The relative composition of different phospholipids in our study was similar to that reported previously ( 57 ).…”

Section: Cardiac Function and Metabolism In Ex Vivo Perfused Working supporting

confidence: 92%

Relationship of glucose and oleate metabolism to cardiac function in lipin-1 deficient (fld) mice

Kok

Kienesberger

Dyck

et al. 2012

Journal of Lipid Research

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of cardiac ATP production ( 1 ). FAs are also incorporated into triacylglycerol (TG), which is stored in lipid droplets. Cardiac TG turnover is rapid ( 2 ) and FAs released from TG can contribute up to 10-20% of ATP production ( 3 ). Plasma FA and TG levels rise in insulin resistance and diabetes ( 4, 5 ), and cardiac FA utilization can increase to supply as much as 90% of ATP ( 6, 7 ). Despite this increase in FAO, FA uptake can exceed the ability of the heart to utilize FAs, leading to excess accumulation of TG in cardiomyocytes ( 6-9 ). The compensatory changes that occur in response to excessive FA availability eventually become maladaptive, and the heart is locked in a pathological and infl exible metabolic state that contributes to cardiac dysfunction ( 6, 7, 10 ). As such, maintenance of metabolic fl exibility is essential for normal cardiac function. Whereas many proteins have been identifi ed to contribute to cardiac FA uptake and metabolism ( 1, 10 ), relatively little information is available about the role of lipin-1 in the heart. Lipin-1 is an important protein involved in regulating both TG synthesis and FAO in other organs ( 11 ).Instead of being considered as mutually antagonistic processes, FAO and TG synthesis are now widely viewed as being companion pathways because augmenting cardiac TG synthesis increases FAO ( 12 ). Moreover, FAs released through lipolysis of endogenous TG stores contribute signifi cantly to FAO ( 3,13 ). Lipin-1 could play a prominent role in this regulation as it is a bifunctional protein involved in regulating both TG synthesis and FAO in the The constant requirement for ATP in the beating heart is satisfi ed by the utilization of diverse substrates, such as fatty acids (FA), glucose, lactate, ketones, and amino acids, with FA oxidation (FAO) providing the majority (50-75%)

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Section: Cardiac Function and Metabolism In Ex Vivo Perfused Working supporting

confidence: 92%

Relationship of glucose and oleate metabolism to cardiac function in lipin-1 deficient (fld) mice

Kok

Kienesberger

Dyck

et al. 2012

Journal of Lipid Research

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“…Early evidence of CL alterations in the failing heart come from studies conducted by O'Rourke, Reibel, and colleagues (42,43), who reported a reduction in the BW, final body weight; sham, animals euthanized at 4 weeks after sham TAB surgery; TAB, animals euthanized at 1 week after thoracic aortic banding surgery; TAB1HS, animals fed an 8% NaCl diet for 3 weeks after a 1 week recovery from TAB surgery. Data are presented as means 6 SEM.…”

Section: Discussionmentioning

confidence: 99%

Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure

Sparagna

Chicco

Murphy

et al. 2007

Journal of Lipid Research

232

202

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The mitochondrial phospholipid cardiolipin is required for optimal mitochondrial respiration. In this study, cardiolipin molecular species and cytochrome oxidase (COx) activity were studied in interfibrillar (IF) and subsarcolemmal (SSL) cardiac mitochondria from Spontaneously Hypertensive Heart Failure (SHHF) and SpragueDawley (SD) rats throughout their natural life span. Fisher Brown Norway (FBN) and young aortic-constricted SHHF rats were also studied to investigate cardiolipin alterations in aging versus pathology. Additionally, cardiolipin was analyzed in human hearts explanted from patients with dilated cardiomyopathy. A loss of tetralinoleoyl cardiolipin (L 4 CL), the predominant species in the healthy mammalian heart, occurred during the natural or accelerated development of heart failure in SHHF rats and humans. L 4 CL decreases correlated with reduced COx activity (no decrease in protein levels) in SHHF cardiac mitochondria, but with no change in citrate synthase (a matrix enzyme) activity. The fraction of cardiac cardiolipin containing L 4 CL became much lower with age in SHHF than in SD or FBN mitochondria. In summary, a progressive loss of cardiac L 4 CL, possibly attributable to decreased remodeling, occurs in response to chronic cardiac overload, but not aging alone, in both IF and SSL mitochondria. This may contribute to mitochondrial respiratory dysfunction during the pathogenesis of heart failure.-Sparagna, G.

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“…45 In the healthy mammalian heart, Ϸ77% of CLs contain 4 linoleoyl acyl chains (L 4 CL), 22 which appears to be important for optimal support of COx activity. 14,25 Decreases in the content or linoleoyl enrichment of CL have been reported in failing hearts from humans and experimental models 13,20,23,46 and have been implicated as the primary causative factor in the lethal x-linked cardioskeletal myopathy known as Barth syndrome. 47 CL deficiency has been specifically associated with impaired mitochondrial enzyme function in a variety of cardiac pathologies, 15 including a progressive decline in COx activity observed during the pathogenesis of HF in the SHHF rat heart.…”

Section: Discussionmentioning

confidence: 99%

Low-Intensity Exercise Training Delays Heart Failure and Improves Survival in Female Hypertensive Heart Failure Rats

et al. 2008

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Abstract-Exercise training improves functional capacity and quality of life in patients with heart failure. However, the long-term effects of exercise on mortality associated with hypertensive heart disease have not been well defined. In the present study, we investigated the effect of low-intensity exercise training on disease progression and survival in female spontaneously hypertensive heart failure rats. Animals with severe hypertension (16 months old) were treadmill trained (14.5 m/min, 45 min/d, 3 d/wk) until they developed terminal heart failure or were euthanized because of age-related complications. Exercise delayed mortality resulting from heart failure (PϽ0.001) and all causes (PϽ0.05) and transiently attenuated the systolic hypertension and contractile dysfunction observed in the sedentary animals but had no effect on cardiac morphology or contractile function in end-stage heart failure. Training had no effect on terminal myocardial protein expression of antioxidant enzymes, calcium handling proteins, or myosin heavy chain isoforms but was associated with higher cytochrome oxidase activity in cardiac mitochondria (PϽ0.05) and a greater mitochondrial content of cardiolipin, a phospholipid that is essential for optimal mitochondrial energy metabolism. In conclusion, low-intensity exercise training significantly delays the onset of heart failure and improves survival in female hypertensive heart failure rats without eliciting sustained improvements in blood pressure, cardiac function, or expression of several myocardial proteins associated with the cardiovascular benefits of exercise. The effects of exercise on cytochrome oxidase and cardiolipin provide novel evidence that training may improve prognosis in hypertensive heart disease by preserving mitochondrial energy metabolism. Key Words: exercise Ⅲ heart failure Ⅲ hypertrophy Ⅲ mortality Ⅲ rats D espite long-standing concern over its safety and use in the treatment of heart failure (HF), accumulating evidence suggests that exercise training is a useful adjuvant therapy in stable HF patients, capable of improving functional capacity, attenuating or reversing pathologic remodeling of the heart, and enhancing quality of life. 1,2 Although a lack of physical activity has been associated with poor prognosis in HF patients, 3,4 whether chronic exercise is an effective means of improving survival has not been clearly established. 5 Several studies indicate that exercise training elicits favorable effects on the myocardium in stable HF patients receiving concomitant pharmacotherapy 1,6 and in various animal models of genetic and surgically induced cardiac hypertrophy and failure. 7-9 However, few studies have examined the independent effect of exercise training on disease progression and mortality in a clinically relevant model of hypertensive HF. The spontaneously hypertensive-HF (SHHF) rat represents a well-characterized congenital model of chronic hypertension progressing to decompensated HF that shares many of the hallmark biochemical and pathophysiologic...

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Altered phospholipid metabolism in pressure-overload hypertrophied hearts

Cited by 47 publications

References 0 publications

Relationship of glucose and oleate metabolism to cardiac function in lipin-1 deficient (fld) mice

Relationship of glucose and oleate metabolism to cardiac function in lipin-1 deficient (fld) mice

Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure

Low-Intensity Exercise Training Delays Heart Failure and Improves Survival in Female Hypertensive Heart Failure Rats

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