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Probing compartment-specific sphingolipids with targeted bacterial sphingomyelinases and ceramidases Research Articles
Sphingolipids contribute to the regulation of cell and tissue homeostasis, and disorders of sphingolipid metabolism lead to diseases such as inflammation, stroke, diabetes, and cancer. Sphingolipid metabolic pathways involve an array of enzymes that reside in specific subcellular organelles, resulting in the formation of many diverse sphingolipids with distinct molecular species based on the diversity of the ceramide (Cer) structure. In order to probe compartment-specific metabolism of sphingolipids in this study, we analyzed the Cer and SM species preferentially produced in the inner plasma membrane (PM), Golgi apparatus,...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Sakamoto, W., Canals, D., Salamone, S., Allopenna, J., Clarke, C. J., Snider, J., Obeid, L. M., Hannun, Y. A. Tags: Research Articles Source Type: research

PCSK9 loss-of-function variants and Lp(a) phenotypes among black US adults Patient-Oriented and Epidemiological Research
The pharmacologic inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) lowers lipoprotein (a) [Lp(a)] concentrations. However, the impact of genetic PCSK9 loss-of-function variants (LOFVs) on Lp(a) is uncertain. We determined the association of PCSK9 LOFVs with Lp(a) measures among black adults. Genotyping for PCSK9 LOFVs was conducted in 10,196 black Reasons for Geographic and Racial Differences in Stroke study participants. Among 241 participants with and 723 randomly selected participants without PCSK9 LOFVs, Lp(a) concentations, apo(a) kringle IV (KIV) repeats (a proxy for isoform size), and oxidized pho...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Mefford, M. T., Marcovina, S. M., Bittner, V., Cushman, M., Brown, T. M., Farkouh, M. E., Tsimikas, S., Monda, K. L., Lopez, J. A. G., Muntner, P., Rosenson, R. S. Tags: Patient-Oriented and Epidemiological Research Source Type: research

Serum apolipoproteins and apolipoprotein-defined lipoprotein subclasses: a hypothesis-generating prospective study of cardiovascular events in T1D Patient-Oriented and Epidemiological Research
APOB, APOC3, and APOE and apolipoprotein-defined lipoprotein subclasses (ADLSs; based on qualitative apolipoprotein complement) have been associated with dyslipidemia and CVD. Our main objective was to define associations of serum apolipoproteins and ADLSs with "any CVD" and "major atherosclerotic cardiovascular events" (MACEs) in a prospective study of T1D. Serum apolipoproteins and ADLSs (14 biomarkers in total) were measured in sera (obtained between 1997 and 2000) from a subset (n = 465) of the Epidemiology of Diabetes Interventions and Complications cohort. Prospective associations of "any CVD" (myocardial infarction,...
Source: The Journal of Lipid Research - July 31, 2019 Category: Lipidology Authors: Basu, A., Bebu, I., Jenkins, A. J., Stoner, J. A., Zhang, Y., Klein, R. L., Lopes-Virella, M. F., Garvey, W. T., Budoff, M. J., Alaupovic, P., Lyons, T. J., the Diabetes Control Complications Trial/Epidemiology of Diabetes Interventions Complications Rese Tags: Patient-Oriented and Epidemiological Research Source Type: research

Diabetes adversely affects phospholipid profiles in human carotid artery endarterectomy plaques Patient-Oriented and Epidemiological Research
Patients with diabetes are at higher risk of developing carotid artery stenosis and resultant stroke. Arachidonoyl phospholipids affect plaque inflammation and vulnerability, but whether diabetic patients have unique carotid artery phospholipidomic profiles is unknown. We performed a comprehensive paired analysis of phospholipids in extracranial carotid endarterectomy (CEA) plaques of matched diabetic and nondiabetic patients and analyzed mass spectrometry-derived profiles of three phospholipids, plasmenyl-phosphatidylethanolamine (pPE), phosphatidylserine (PS), and phosphatidylinositol (PI), in maximally (MAX) and minimal...
Source: The Journal of Lipid Research - April 1, 2018 Category: Lipidology Authors: Zayed, M. A., Hsu, F.-F., Patterson, B. W., Yan, Y., Naim, U., Darwesh, M., De Silva, G., Yang, C., Semenkovich, C. F. Tags: Patient-Oriented and Epidemiological Research Source Type: research

Acid sphingomyelinase promotes mitochondrial dysfunction due to glutamate-induced regulated necrosis Research Articles
Inhibiting the glutamate/cystine antiporter system xc–, a key antioxidant defense machinery in the CNS, could trigger a novel form of regulated necrotic cell death, ferroptosis. The underlying mechanisms of system xc–-dependent cell demise were elucidated using primary oligodendrocytes (OLs) treated with glutamate to block system xc– function. Pharmacological analysis revealed ferroptosis as a major contributing factor to glutamate-initiated OL death. A sphingolipid profile showed elevations of ceramide species and sphingosine that were preventable by inhibiting of an acid sphingomyelinase (ASM) activity....
Source: The Journal of Lipid Research - February 1, 2018 Category: Lipidology Authors: Novgorodov, S. A., Voltin, J. R., Gooz, M. A., Li, L., Lemasters, J. J., Gudz, T. I. Tags: Research Articles Source Type: research

Association of peripheral differential leukocyte counts with dyslipidemia risk in Chinese patients with hypertension: insight from the China Stroke Primary Prevention Trial Patient-Oriented and Epidemiological Research
The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10,866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte, neutrophil, and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte counts were consistently and positively associated with serum total cholesterol (TC), LDL cholesterol (LDL-C), and TG levels (all ...
Source: The Journal of Lipid Research - December 31, 2016 Category: Lipidology Authors: Liu, Y., Kong, X., Wang, W., Fan, F., Zhang, Y., Zhao, M., Wang, Y., Wang, Y., Wang, Y., Qin, X., Tang, G., Wang, B., Xu, X., Hou, F. F., Gao, W., Sun, N., Li, J., Venners, S. A., Jiang, S., Huo, Y. Tags: Patient-Oriented and Epidemiological Research Source Type: research

Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans Thematic Reviews
Epidemiological, genetic association, and Mendelian randomization studies have provided strong evidence that lipoprotein (a) [Lp(a)] is an independent causal risk factor for CVD, including myocardial infarction, stroke, peripheral arterial disease, and calcific aortic valve stenosis. Lp(a) levels >50 mg/dl are highly prevalent (20% of the general population) and are overrepresented in patients with CVD and aortic stenosis. These data support the notion that Lp(a) should be a target of therapy for CVD event reduction and to reduce progression of aortic stenosis. However, effective therapies to specifically reduce plasma ...
Source: The Journal of Lipid Research - March 1, 2016 Category: Lipidology Authors: Graham, M. J., Viney, N., Crooke, R. M., Tsimikas, S. Tags: Thematic Reviews Source Type: research

Rare coding variation in paraoxonase-1 is associated with ischemic stroke in the NHLBI Exome Sequencing Project Patient-Oriented and Epidemiological Research
HDL-associated paraoxonase-1 (PON1) is an enzyme whose activity is associated with cerebrovascular disease. Common PON1 genetic variants have not been consistently associated with cerebrovascular disease. Rare coding variation that likely alters PON1 enzyme function may be more strongly associated with stroke. The National Heart, Lung, and Blood Institute Exome Sequencing Project sequenced the coding regions (exomes) of the genome for heart, lung, and blood-related phenotypes (including ischemic stroke). In this sample of 4,204 unrelated participants, 496 had verified, noncardioembolic ischemic stroke. After filtering, 28 ...
Source: The Journal of Lipid Research - May 28, 2014 Category: Lipidology Authors: Kim, D. S., Crosslin, D. R., Auer, P. L., Suzuki, S. M., Marsillach, J., Burt, A. A., Gordon, A. S., Meschia, J. F., Nalls, M. A., Worrall, B. B., Longstreth, W. T., Gottesman, R. F., Furlong, C. E., Peters, U., Rich, S. S., Nickerson, D. A., Jarvik, G. P Tags: Patient-Oriented and Epidemiological Research Source Type: research