Phenotype-genotype Correlation in CD36 Deficiency Types I and II

Yanai, Hidekatsu; Chiba, Hitoshi; Fujiwara, Hironobu; Morimoto, Mie; Abé, Keisuke; Yoshida, Shigeru; Takahashi, Yukihiro; Fuda, Hirotoshi; Hui, Shu‐Ping; Akita, Harukuni; Kobayashi, Kunihiko; Matsuno, Kōichirō

doi:10.1055/s-0037-1614041

Cited by 50 publications

(52 citation statements)

References 51 publications

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“…The results also raise the possibility that the absence of CD36 in 5% of the Asian population offers protection against the platelet-activation component of amyloid-based diseases, a result that has important implications. 34 Recent publications described the presence of amyloid-␤ in platelet-derived microparticles in healthy subjects 35 and in patients with atherosclerotic disease 36 and type 2 Diabetes Mellitus. 37 These particles are a source of tissue factor, which is the prime initiator of coagulation.…”

Section: Discussionmentioning

confidence: 99%

Activation of Human Platelets by Misfolded Proteins

Herczenik

Bouma

Korporaal

et al. 2007

ATVB

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Objective-Protein misfolding diseases result from the deposition of insoluble protein aggregates that often contain fibrils called amyloid. Amyloids are found in Alzheimer disease, atherosclerosis, diabetes mellitus, and systemic amyloidosis, which are diseases where platelet activation might be implicated. Methods and Results-We induced amyloid properties in 6 unrelated proteins and found that all induced platelet aggregation in contrast to fresh controls. Amyloid-induced platelet aggregation was independent of thromboxane A 2 formation and ADP secretion but enhanced by feedback stimulation through these pathways. Treatments that raised cAMP (iloprost), sequestered Ca 2ϩ (BAPTA-AM) or prevented amyloid-platelet interaction (sRAGE, tissue-type plasminogen activator [tPA]) induced almost complete inhibition. Modulation of the function of CD36 (CD36 Ϫ/Ϫ mice), p38 MAPK (SB203580), COX-1 (indomethacin), and glycoprotein Ib␣ (Nk-protease, 6D1 antibody) induced Ϸ50% inhibition. Interference with fibrinogen binding (RGDS) revealed a major contribution of ␣ IIb ␤ 3 -independent aggregation (agglutination). Conclusions-Protein misfolding resulting in the appearance of amyloid induces platelet aggregation. Amyloid activates platelets through 2 pathways: one is through CD36, p38 MAPK , thromboxane A 2 -mediated induction of aggregation; the other is through glycoprotein Ib␣-mediated aggregation and agglutination. The platelet stimulating properties of amyloid might explain the enhanced platelet activation observed in many diseases accompanied by the appearance of misfolded proteins with amyloid. Key Words: amyloid Ⅲ platelet activation Ⅲ sRAGE Ⅲ tissue plasminogen activator Ⅲ CD36 Ⅲ glycoprotein Ib␣ P roteins typically adopt a well-defined 3-dimensional structure. There is now an increasing amount of evidence that abnormalities in this process have far reaching consequences for human health. Certain mutations and posttranslational modifications such as glycation and oxidation interfere with proper folding, resulting in protein misfolding, aggregation, and ultimately polymerization into insoluble fibrils called amyloid. 1,2 The term amyloidosis defines a group of systemic and localized diseases associated with the deposition of amyloid in different tissues. Alzheimer disease is caused by abnormal folding of amyloid-␤ and formation of amyloid-rich plaques that obstruct neurons and microvessels of the brain. 3 One has argued that these plaques cause the hyperreactivity of platelets observed in these patients as illustrated by P-selectin positive platelets and increased levels of urinary thromboxane A 2 metabolite. 4,5 An environmental risk factor for Alzheimer disease is Herpes Simplex virus. It contains glycoprotein B, a protein fragment that assembles into fibrils that are ultrastructurally indistinguishable from amyloid-␤. 6 Protein misfolding is not restricted to Alzheimer disease but is a common feature in the pathology of atherosclerosis, diabetes mellitus, and systemic amyloidosis. 7-9 Atherosclerotic plaques contain ...

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Section: Discussionmentioning

confidence: 99%

Activation of Human Platelets by Misfolded Proteins

Herczenik

Bouma

Korporaal

et al. 2007

ATVB

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“…A lack of CD36 expression in platelets was first identified in a thrombocytopenic patient refractory to an HLA-matched platelet transfusion [9]. The incidence of types I and II CD36 deficiency among healthy Japanese volunteers were 1.0% and 5.8%, respectively [20]. From these two pieces of evidence, CD36-deficient individuals are thought to be apparently healthy without evidence of a hemostatic problem.…”

Section: Discussionmentioning

confidence: 99%

CD36 deficiency and absent myocardial iodine-123-(R,S)-15-(p-iodophenyl)-3-methylpentadecanoic acid uptake in a girl with cardiomyopathy

et al. 2003

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“…16 Genetic polymorphisms have been identified in Asian and African populations, which can lead to deficient or absent expression of CD36. 17,18 Monocyte-derived macrophages isolated from homozygous mutant patients bound 40% less OxLDL and accumulated 40% less cholesterol ester than cells derived from normal controls. 19 More recently, using macrophages derived from mice lacking both CD36 and the class A scavenger receptors, we demonstrated that the predominant receptor involved in recognition of pro-atherogenic LDL (either mildly oxidized by copper sulfate or oxidized by the myeloperoxide/hydrogen peroxide/nitrite system) was CD36; the combined effect of absence of both scavenger receptors was not significantly greater than absence of CD36 alone.…”

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confidence: 99%

Stem Cell Transplantation Reveals That Absence of Macrophage CD36 Is Protective Against Atherosclerosis

Febbraio

Guy

Silverstein

2004

ATVB

155

109

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Objective-CD36 is expressed on multiple cell types and has numerous functions, a subset of which can impact on atherogenesis.In previous work, we demonstrated that CD36 absence was protective against lesion formation. The current objective was to determine whether absence of macrophage CD36 alone was protective. Methods and Results-Lethal irradiation and stem cell transfer were used to create chimeric mice that did or did not express macrophage CD36 in the context of the Apo E-null model of atherosclerosis. After engraftment, mice were fed a Western diet for 12 weeks. White cell counts, plasma levels of lipoproteins, triacylglycerol, and nonesterified fatty acids were determined, and glucose tolerance tests were preformed. Lesion area was assessed quantitatively after oil red O staining. Mice lacking CD36 in macrophages alone were profoundly protected against atherosclerosis (88.1% reduction of lesion area throughout the aortic tree). Re-introduction of macrophage CD36 resulted in a 2.11-fold increase in lesion area. There were no differences in engraftment, macrophage recruitment, glucose tolerance, weight, and total, low-density lipoprotein, and high-density lipoprotein cholesterol among the groups. Lesions contained similar percent macrophage antigen-positive area. Key Words: CD36 Ⅲ atherosclerosis Ⅲ Apo E-null mice Ⅲ scavenger receptor Ⅲ macrophages C ellular cholesterol homeostasis is tightly regulated such that cells have an adequate supply under varying dietary conditions. 1 For most cell types, excessive accumulation of cholesterol does not occur and would have toxic implications. 2 Macrophages, by virtue of their scavenger function, internalize cholesterol-laden modified lipoproteins. Uncontrolled cholesterol accumulation in macrophages may result as an adaptive mechanism in response to excessive lipid load and lead to foam cell formation. These appear grossly as the initial lesion in atherosclerosis, the fatty streak. 3 Oxidative modification of low-density lipoprotein (LDL) has been hypothesized to be a key event in the conversion of LDL to a pro-atherogenic form recognized by macrophage scavenger receptors. 4,5 Thus, internalization of oxidized LDL (OxLDL) by macrophages is an early and potentially pivotal event which, if inhibited through intervention at the level of the scavenger receptor, may delay the atherosclerotic process. Conclusion-ProtectionPrevious in vitro work has supported a significant role for the class B scavenger receptor, CD36, in atherogenesis. 6,7 We and others demonstrated that CD36 bound OxLDL in a saturable manner; binding, internalization, and degradation of OxLDL were increased substantially in CD36 transfected cells. 6 -8 Regulation of CD36 expression was also highly suggestive of an important role in atherosclerosis. 9 -15 Unlike the LDL receptor, which is downregulated by cellular cholesterol/cholesterol ester, expression of CD36 was enhanced by cellular cholesterol/cholesterol ester content and downregulated by its depletion. 10 We also showed that IL-4 and macrophage-c...

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Phenotype-genotype Correlation in CD36 Deficiency Types I and II

Cited by 50 publications

References 51 publications

Activation of Human Platelets by Misfolded Proteins

Activation of Human Platelets by Misfolded Proteins

CD36 deficiency and absent myocardial iodine-123-(R,S)-15-(p-iodophenyl)-3-methylpentadecanoic acid uptake in a girl with cardiomyopathy

Stem Cell Transplantation Reveals That Absence of Macrophage CD36 Is Protective Against Atherosclerosis

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