Is CD36 Deficiency an Etiology of Hereditary Hypertrophic Cardiomyopathy?

Tanaka, Takao; Sohmiya, Koichi; Kawamura, Keishiro

doi:10.1006/jmcc.1996.0257

Cited by 127 publications

(97 citation statements)

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“…Consistent with this observation, a large compensatory increase in myocardial glucose utilization has been measured in both species (16). In addition, the CD36-deficient murine heart exhibits signs of hypertrophy (Table 1), and association of CD36 deficiency with hypertrophic cardiomyopathy has been reported in humans (15,17,27,55).…”

Section: Discussionmentioning

confidence: 90%

Myocardial recovery from ischemia is impaired in CD36-null mice and restored by myocyte CD36 expression or medium-chain fatty acids

Irie

Krukenkamp

Brinkmann

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Long-chain fatty acid uptake, which provides a large part of myocardial energy, is impaired in human and murine hearts deficient in the membrane fatty acid translocase, FAT͞CD36. We examined myocardial function in CD36-null mice using the working heart. Fatty acid oxidation and stores of glycogen, triglycerides, and ATP were reduced in CD36-deficient hearts and were restored to WT levels by rescue of myocyte CD36. Under normal perfusion conditions, CD36-null hearts had similar cardiac outputs and end-diastolic pressures as WT or transgenic hearts. After 6 min of ischemia, cardiac output decreased by 41% and end diastolic pressure tripled for CD36-null hearts, with no significant changes in WT or transgenic hearts. Null hearts also failed more frequently after ischemia as compared with WT or transgenics. To dissect out contribution of fatty acid uptake, a perfusate-lacking fatty acids was used. This decreased cardiac output after ischemia by 30% in WT hearts as compared with 50% for CD36-deficient hearts. End diastolic pressure, a negative index of myocardial performance, increased after ischemia in all heart types. Addition to the perfusate of a medium-chain fatty acid (caprylic acid) that does not require CD36 for uptake alleviated poor ischemic tolerance of CD36-null hearts. In summary, recovery from ischemia is compromised in CD36-deficient hearts and can be restored by CD36 rescue or by supplying medium-chain fatty acids. It would be important to determine whether the findings apply to the human situation where polymorphisms of the CD36 gene are relatively common.CD36 rescue ͉ working heart ͉ fatty acid oxidation F atty acid (FA) uptake consists of two components, passive diffusion and carrier-mediated transport specific for FA with Ͼ8-10 carbons (1). An 88-kDa glycoprotein, FAT (2), a homolog of human CD36 (3, 4) was implicated in FA transport by labeling with the transport inhibitor sulfo-N-succinimidyl oleate (1, 5). The role of FAT͞CD36 in FA uptake was confirmed by studies of mice with CD36 deficiency or overexpression (6, 7). CD36 is abundant in the heart (2, 8), and its deficiency is associated with a 60-80% decrease in myocardial FA uptake (9, 10) and with a severalfold compensatory increase in glucose utilization (11).There is strong evidence for a critical role of CD36-facilitated FA uptake during muscle contraction, which was shown to recruit the protein to the plasma membrane (12). Muscle-targeted overexpression of CD36 enhanced FA oxidation in response to contraction severalfold (7). In line with this, CD36-null mice (6) perform poorly on treadmill and swimming tests (A.I., unpublished observations). However the impact of CD36 deficiency on the performance of the heart, which relies on FA for energy, remains unknown. Such information may have clinical relevance because incidence of CD36 deficiency in humans ranges between 0.3% and 18.5% depending on the population (13). CD36-deficient humans have a defect in myocardial FA uptake (14, 15) that is similar in magnitude to that observed in the CD36-...

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Section: Discussionmentioning

confidence: 90%

Myocardial recovery from ischemia is impaired in CD36-null mice and restored by myocyte CD36 expression or medium-chain fatty acids

Irie

Krukenkamp

Brinkmann

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…On the other hand, a CD36 abnormality may be associated with some form of cardiac hypertrophy. 5,16,19 Two previous reports 5, 16 demonstrated a correlation between impaired cardiac BMIPP uptake and CD36 expression deficiency in 11 patients with hypertrophic cardiomyopathy; 3 patients with type I CD36 deficiency showed no cardiac uptake of BMIPP and 4 out of 8 patients with type II CD36 deficiency showed reduced BMIPP uptake. In these studies, however, CD36-related genes were not investigated.…”

Section: Discussionmentioning

confidence: 93%

“…However, the presence or absence of a cardiac defect of long-chain fatty acid (BMIPP or 9-MPA) uptake in these healthy subjects showing CD36 deficiency is unclear. Although CD36 expression was not investigated in the aortic stenosis patient who showed cardiac hypertrophy but normal uptakes of BMIPP and 9MPA, previous reports 5, 16 have demonstrated that all patients showing a global BMIPP defect have type I CD36 deficiency. Our recent observations (unpublished data) showed that all of 4 hypertrophic cardiomyopathy patients showing no cardiac BMIPP uptake were type I CD36 deficiency and that 12 (29%) of 41 hypertrophic cardiomyopathy patients who showed regional BMIPP defect were type II CD36 deficiency, indicating a close correlation between CD36 molecule expression and impaired cardiac uptake of long-chain free fatty acids.…”

Section: Discussionmentioning

confidence: 94%

Scintigraphic Evidence for a Specific Long-Chain Fatty Acid Transporting System Deficit and the Genetic Background in a Patient With Hypertrophic Cardiomyopathy

et al. 1999

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“…Studies utilizing a nonmetabolizable fatty acid analogue, BMIPP, suggest that FAT/CD36 accounts for 50% to 80% of the total fatty acid uptake by the heart. 6 Polymorphisms in human FAT/CD36 occur in Asian and African populations at a relatively high frequency, and there have been reports that these deficient individuals have reduced cardiac fatty acid uptake [7][8][9][10][11][12][13][14] and cardiac abnormalities. However, considerable controversy exists with regard to the potential involvement of FAT/CD36 deficiency in the development of hypertrophic cardiomyopathy, 7,[15][16][17][18][19] and it has not been directly proven whether patients with FAT/ CD36 deficiency have reduced cardiac fatty acid oxidation rates or energetically compromised hearts.…”

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confidence: 99%

Fatty Acid Translocase/CD36 Deficiency Does Not Energetically or Functionally Compromise Hearts Before or After Ischemia

et al. 2004

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Background-Evidence from humans suggests that fatty acid translocase (FAT)/CD36 deficiency can lead to functionally and/or energetically compromised hearts, but the data are equivocal, and the subject remains controversial. In this report we assessed the contribution of FAT/CD36 to overall fatty acid oxidation rates in the intact heart and determined the effect of FAT/CD36 on energy metabolism during reperfusion of ischemic hearts. Methods and Results-Isolated working hearts from wild-type and FAT/CD36-knockout (KO) mice were perfused with Krebs-Henseleit solution containing 0..5 mmol/L calcium, and 100 U/mL insulin at a preload pressure of 11.5 mm Hg and afterload pressure of 50 mm Hg. Hearts were aerobically perfused for 30 minutes or aerobically perfused for 30 minutes, followed by 18 minutes of global no-flow ischemia and 40 minutes of aerobic reperfusion. Rates of fatty acid oxidation in FAT/CD36-KO hearts were significantly lower than in wild-type hearts at both concentrations of palmitate (0.4 or 1.2 mmol/L). In addition, hearts from FAT/CD36-KO mice displayed a compensatory increase in glucose oxidation rates. On aerobic reperfusion after ischemia, cardiac work of FAT/CD36-KO hearts recovered to the same extent as wild-type hearts. Conclusions-FAT/CD36-deficient

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Is CD36 Deficiency an Etiology of Hereditary Hypertrophic Cardiomyopathy?

Cited by 127 publications

References 0 publications

Myocardial recovery from ischemia is impaired in CD36-null mice and restored by myocyte CD36 expression or medium-chain fatty acids

Myocardial recovery from ischemia is impaired in CD36-null mice and restored by myocyte CD36 expression or medium-chain fatty acids

Scintigraphic Evidence for a Specific Long-Chain Fatty Acid Transporting System Deficit and the Genetic Background in a Patient With Hypertrophic Cardiomyopathy

Fatty Acid Translocase/CD36 Deficiency Does Not Energetically or Functionally Compromise Hearts Before or After Ischemia

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