Fu Sang Luk's research while affiliated with San Francisco VA Medical Center and other places

Publications (9)

Chapter
Plasma lipoproteins are essential vehicles of lipid distribution for cellular energy and structural requirements as well as for excretion of lipid excess. Imbalances in lipoprotein metabolism are known to contribute to metabolic diseases ranging from vascular inflammation and atherosclerosis to obesity and diabetes. The lipid and protein cargo carr...
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We recently reported that immunosuppression with FTY720 improves cardiac function and extends longevity in Hypomorphic ApoE mice deficient in scavenger receptor Type-BI expression, also known as the HypoE/SR-BI mouse model of diet-induced coronary atherosclerosis and myocardial infarction (MI). In this study we tested the impact of FTY720 on cardia...
Article
Apolipoprotein E (apoE) exerts anti-inflammatory properties that protect against atherosclerosis and other inflammatory diseases. However, mechanisms by which apoE suppresses the cellular activation of leukocytes commonly associated with atherosclerosis remain incompletely understood. To test the hypothesis that apoE suppresses inflammation and ath...
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: FTY720, an analogue of sphingosine-1-phosphate, is cardioprotective during acute injury. Whether long-term FTY720 affords cardioprotection is unknown. Here, we report the effects of oral FTY720 on ischemia/reperfusion injury and in hypomorphic apoE mice deficient in SR-BI receptor expression (ApoeR61/SRB1 mice), a model of diet-induced coronary a...
Article
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To study atherosclerosis regression in mice after plasma lipid reduction to moderately elevated apolipoprotein B (apoB)-lipoprotein levels. Chow-fed hypomorphic Apoe mice deficient in low-density lipoprotein receptor expression (Apoe(h/h)Ldlr(-/-)Mx1-cre mice) develop hyperlipidemia and atherosclerosis. These mice were studied before and after indu...
Article
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Apolipoprotein (apo) E4 is an established risk factor for atherosclerosis, but the structural components underlying this association remain unclear. ApoE4 is characterized by 2 biophysical properties: domain interaction and molten globule state. Substituting Arg-61 for Thr-61 in mouse apoE introduces domain interaction without molten globule state,...

Citations

... Ouimet et al. reported that miR-33 can regulate macrophage inflammation and reduce plaque inflammation by potentiating M2 macrophage polarization and Treg induction [21]. In addition, Li et al. found that apolipoprotein E promotes miR-146a in monocytes and macrophages to inhibit inflammation driven by NF-κB [22]. Furthermore, it was found by Tian et al. that miR-194 attenuated the generation of proinflammatory cytokine in palmitic acid-induced THP-1 Cells [23]. ...
... SR-B1 KO/ApoER61 h/h mice rapidly respond to the challenge of an atherogenic diet with plaque formation both in the aortic root and coronary arteries, recapitulating many features of human ASCVD [20]. SR-B1 KO/ApoER61 h/h mice fed with HFC-Control diet readily developed plaques in highly vulnerable regions along the arterial tree, in agreement with previously published data [12,28,29,50]. Supplementation with RWGP significantly reduced atherosclerotic lesion development. ...
... Additionally, attenuated atherosclerosis development was associated with reduced percentage of hearts exhibiting myocardial infarction and improvement in cardiac ejection fraction in the HFC-RWGP group. Recovery of heart function has also been reported in SR-B1 KO/ApoER61 h/h mice after the administration of the immunosuppressant FTY720 [50,53]. Our findings are interesting since the compositional analysis of HFC-RWGP diet showed an increase in total tocopherol content, more specifically in α-tocopherol, the most active member of vitamin E lipid-soluble antioxidant compounds. ...
... In cardiovascular disease, increased binding of APOE4 to VLDLs leads to LDL receptor downregulation and increased LDL plasma levels (i.e., 'bad cholesterol' that can build up in the arteries) 23 ; such an increase in LDL cholesterol is also a risk factor for dementia, which is thought to alter the deposition and/or clearance of Aβ, although the mechanism is not fully understood 24 . These key findings highlight that a specific domain interaction could be an important therapeutic target for ameliorating impairments in APOE4 in humans [25][26][27] . ...
... GAPDH rabbit polyclonal antibody (sc-25778) was purchased from Santa Cruz. Lipoprotein deficient serum (LPDS) was prepared as previously described (56). In brief, FBS was adjusted to 1.21 g/ml, then centrifuged to separate lipoprotein from sera. ...
... and atherosclerosis are regulated by the expression of cellular apolipoprotein e (14). a defect in the nf-κB/mir-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy (15). ...
... Furthermore, temporal Cre-mediated gene repair of the Apoe h/h locus revealed a role for apoE in promoting the regression of atherosclerosis beyond reducing plasma lipid levels [18]. Breeding Apoe h/h mice with mice deficient in LDL receptor gene expression led to new opportunities to study the process of apoE in atherosclerosis progression [7] and its regression [19]. Likewise, breeding Apoe h/h mice with mice deficient in the scavenger receptor class B type-1 (SRB1 −/− Apoe h/h mice) led to a model of diet-induced occlusive coronary atherosclerosis, myocardial infarction and fatal ischemic heart disease [20,21]. ...