scholarly journals Knockdown of lncRNA ENST00000609755.1 Confers Protection Against Early oxLDL-Induced Coronary Heart Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi Sun ◽  
Shuna Huang ◽  
Chunyu Wan ◽  
Qishuang Ruan ◽  
Xiaoxu Xie ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Peripheral Blood ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Peripheral Blood Leukocyte ◽  
Loss Of Function ◽  
Human Coronary Artery ◽  
Injury Model

Background: This study investigated the association between long non-coding RNAs (lncRNAs) and coronary heart disease (CHD) and further elucidated the potential biological roles of lncRNAs in CHD pathogenesis.Methods: A case-control study (590 patients and 590 controls) was conducted from February 2017 and March 2019 in Fuzhou, China. Environmental factors were investigated using questionnaires and physical examinations. Five representative lncRNAs were screened using lncRNA microarray (peripheral blood in 5 cases and 5 controls) and further verified by quantitative real-time polymerase chain reaction (peripheral blood leukocyte in 100 cases and 100 controls). Oxidized low-density lipoprotein (oxLDL) was used to induce a human coronary artery endothelial cell (HCAECs) injury model, and loss of function was used to elucidate the role of lncRNA ENST00000609755.1 (lnc-MICALL2-2) in oxLDL-induced HCAECs injury.Results: A total of 320 lncRNAs were found dysregulated in CHD patients (fold change> 2, p < 0.05). The results of a discovery microarray, population verification and HCAEC experiments suggested the lnc-MICALL2-2 is upregulated in CHD subjects and in an oxLDL-induced HCAECs injury model. Conversely, lnc-MICALL2-2 inhibition in vitro attenuated the effects of oxLDL on HCAECs morphology, proliferation, and apoptosis.Conclusion: Elevated expression of lnc-MICALL2-2 is an independent risk factor for CHD, and knockdown subsequently confers protection against early pathological processes of oxLDL-induced CHD.

Abstract 9793: Pcsk9 Loss-of-function Variants, Low-density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data From the REGARDS Study and CHARGE Consortium

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Shia T Kent ◽  
Robert S Rosenson ◽  
Christy L Avery ◽  
Adolfo Correa ◽  
Steven R Cummings ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Association Studies ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Loss Of Function ◽  
Low Density Lipoprotein Cholesterol ◽  
Regards Study

Introduction: PCSK9 loss-of-function variants are associated with reduced low-density lipoprotein cholesterol (LDL-C) concentrations. Genetic association studies of PCSK9 loss-of-function variants allow for the examination of the effects of lifetime low LDL-C on cardiovascular outcomes. Hypothesis: PCSK9 loss-of-function variants are associated with lower concentrations of LDL-C and reduced risk of coronary heart disease (CHD) and stroke. Methods: We studied the association of PCSK9 loss-of-function Y142X and C679X nonsense variants (n=366; 2.1%) in 17,459 African Americans (AAs) and R46L missense variants (n=962; 3.1%) in 31,469 whites with LDL-C, CHD and stroke in the US-based REasons for Geographic And Racial Difference in Stroke (REGARDS) study and 8 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We combined multivariable adjusted differences in LDL-C between participants with and without PCSK9 variants across studies using inverse-variance weighted fixed-effects models. We calculated unadjusted odds ratios (ORs) for associations between PCSK9 variants and incident CHD (851 events in AAs and 2,662 events in whites) and stroke (523 events in AAs and 1,660 events in whites) using pooled Mantel-Haenszel estimates with continuity correction factors. Results: In the pooled cohorts, PCSK9 variants were associated with 36 mg/dL (95% confidence interval [CI]: 31, 40) lower LDL-C in AAs and 13 mg/dL (95% CI: 11, 16) lower LDL-C in whites. PCSK9 variants were associated with a pooled OR for CHD of 0.51 (95% CI: 0.28, 0.92) in AAs and 0.82 (95% CI: 0.63, 1.06) in whites. PCSK9 variants were not associated with incident stroke (OR=0.84 [95% CI: 0.48, 1.47] in AAs and OR=1.06 [95% CI: 0.80, 1.41] in whites). Conclusions: These results provide evidence that PCSK9 variants are associated with lifelong reduction in LDL-C and may lead to lower CHD risk, but no effect on stroke risk.

Clinical significance of lipoprotein size and risk for coronary atherosclerosis

1995 ◽  
Vol 41 (1) ◽  
pp. 147-152 ◽  
Author(s):  
P S Roheim ◽  
B F Asztalos
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Apo B ◽  
Ldl Particles ◽  
Increased Risk ◽  
Lipoprotein Size

Abstract Correlation between coronary heart disease and lipoprotein size and composition is well documented. Within the low-density lipoprotein (LDL) family the small LDL particles are associated with increased risk of coronary heart disease. These particles also have increased apolipoprotein (apo) B content. The appearance of these small LDL particles is the manifestation of complex alteration of plasma lipoprotein metabolism. The LDL size is influenced by genetic, endocrine, and environmental factors. Within the high-density lipoprotein (HDL) family the decrease of larger HDL2 particles is associated with coronary heart disease. HDLs can also be separated according to their apoprotein composition into particles containing lipoprotein (Lp)A-I only and particles containing LpA-I and LpA-II. Most studies have shown that the concentration of LpA-I-only particles decreases in coronary heart disease. HDLs are remodeled in the circulation and this remodeling continues in vitro after the blood is taken. Therefore adequate preservation of blood samples is necessary.

scholarly journals Liver X Receptor Nuclear Receptors Are Transcriptional Regulators of Dendritic Cell Chemotaxis

2018 ◽  
Vol 38 (10) ◽  
Author(s):  
Susana Beceiro ◽  
Attila Pap ◽  
Zsolt Czimmerer ◽  
Tamer Sallam ◽  
Jose A. Guillén ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Low Density Lipoprotein ◽  
Myeloid Cells ◽  
Density Lipoprotein ◽  
Loss Of Function ◽  
Transcriptional Responses ◽  
Cd38 Expression ◽  
The Impact

ABSTRACTThe liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DCs), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migrationin vitroandin vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished the LXR-dependent induction of DC chemotaxis. Using the low-density lipoprotein receptor-deficient (LDLR−/−) LDLR−/−mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for the efficient emigration of DCs in response to chemotactic signals during inflammation.

Isolation of plasma small-dense low-density lipoprotein using a simple air-driven ultracentrifuge and quantification using immunassay of apolipoprotein B

2004 ◽  
Vol 42 (1) ◽  
Author(s):  
Valentine C. Menys ◽  
Yifen Liu ◽  
Michael I. Mackness ◽  
See Kwok ◽  
Muriel J. Caslake ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Coronary Heart Disease Risk ◽  
Apolipoprotein B ◽  
Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Heart Disease Risk

AbstractSmall-dense low-density lipoprotein (SD-LDL) is associated with coronary heart disease risk. Current methods for its quantification are expensive, complex and time-consuming. Plasma was adjusted to a density (D) of 1.044 g/ml in a volume of 0.18 ml and centrifuged in a Beckman Airfuge at 160 000×

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