scholarly journals Plasma exosome-derived microRNAs expression profiling and bioinformatics analysis under cross-talk between increased low-density lipoprotein cholesterol level and ATP-sensitive potassium channels variant rs1799858

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Cheng Liu ◽  
Yanxian Lai ◽  
Songsong Ying ◽  
Junfang Zhan ◽  
Yan Shen
Keyword(s):  
Potassium Channels ◽  
Expression Profile ◽  
Cross Talk ◽  
Target Genes ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Abstract Background Exosome-derived microRNAs (exo-miRs) as messengers play important roles, in the cross-talk between genetic [ATP-sensitive potassium channels (KATP) genetic variant rs1799858] and environmental [elevated serum low-density lipoprotein cholesterol (LDL-C) level] factors, but the plasma exo-miRs expression profile and its role in biological processes from genotype to phenotype remain unclear. Methods A total of 14 subjects with increased LDL-C serum levels (≥ 1.8 mmol/L) were enrolled in the study. The KATP rs1799858 was genotyped by the Sequenom MassARRAY system. The plasma exo-miRs expression profile was identified by next-generation sequencing. Results 64 exo-miRs were significantly differentially expressed (DE), among which 44 exo-miRs were up-regulated and 20 exo-miRs were down-regulated in those subjects carrying T-allele (TT + CT) of rs1799858 compared to those carrying CC genotype. The top 20 up-regulated DE-exo-miRs were miR-378 family, miR-320 family, miR-208 family, miR-483-5p, miR-22-3p, miR-490-3p, miR-6515-5p, miR-31-5p, miR-210-3p, miR-17-3p, miR-6807-5p, miR-497-5p, miR-33a-5p, miR-3611 and miR-126-5p. The top 20 down-regulated DE-exo-miRs were let-7 family, miR-221/222 family, miR-619-5p, miR-6780a-5p, miR-641, miR-200a-5p, miR-581, miR-605-3p, miR-548ar-3p, miR-135a-3p, miR-451b, miR-509-3-5p, miR-4664-3p and miR-224-5p. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently implemented to identify the top 10 DE-exo-miRs related specific target genes and signaling pathways. Only 5 DE-exo-miRs were validated by qRT-PCR as follows: miR-31-5p, miR-378d, miR-619-5p, miR-320a-3p and let-7a-5p (all P < 0.05). Conclusion These results firstly indicated the plasma exo-miRs expression profile bridging the link between genotype (KATP rs1799858) and phenotype (higher LDL-C serum level), these 5 DE-exo-miRs may be potential target intermediates for molecular intervention points.

scholarly journals Coronary Microvascular Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Artery Disease Is Associated With Elevated Serum Homocysteine Levels

2020 ◽  
Vol 9 (19) ◽  
Author(s):  
Ali Ahmad ◽  
Michel T. Corban ◽  
Takumi Toya ◽  
Jaskanwal D. Sara ◽  
Ben Lerman ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Nonobstructive Coronary Artery Disease ◽  
Serum Homocysteine ◽  
Artery Disease

Background Elevated levels of serum homocysteine, via impaired nitric oxide production, and coronary microvascular dysfunction are associated with increased risk of major adverse cardiovascular events. However, whether serum homocysteine levels and coronary microvascular endothelial dysfunction (CMED) are linked remains unknown. Methods and Results This study included 1418 patients with chest pain or an abnormal functional stress test and with nonobstructive coronary artery disease (<40% angiographic stenosis), who underwent CMED evaluation with functional angiography and had serum homocysteine levels measured. Patients were classified as having normal microvascular function versus CMED. Patients in the CMED group (n=743; 52%) had higher mean age (52.1±12.2 versus 50.0±12.4 years; P <0.0001), higher body mass index (29.1 [25.0–32.8] versus 27.5 [24.2–32.4]; P =0.001), diabetes mellitus (12.5% versus 9.4%; P =0.03), and fewer women (63.5% versus 68.7%; P =0.04) compared with patients in the normal microvascular function group. However, they had lower rates of smoking history, and mildly lower low‐density lipoprotein cholesterol levels. Serum homocysteine levels were significantly higher in patients with CMED, and the highest quartile of serum homocysteine level (>9 µmol/L) was an independent predictor of CMED (odds ratio, 1.34 [95% CI, 1.03–1.75]; P =0.03) after adjustment for age; sex; body mass index; chronic kidney disease (CKD); diabetes mellitus; smoking exposure; low‐density lipoprotein cholesterol; high‐density lipoprotein cholesterol and triglycerides; and aspirin, statin, and B vitamin use. Conclusions Patients with CMED have significantly higher levels of serum homocysteine. Elevated serum homocysteine levels were associated with a significantly increased odds of an invasive diagnosis of CMED. The current study supports a potential role for homocysteine for diagnosis and target treatment in the patients with early coronary atherosclerosis.

Niacin Treatment of Hypercholesterolemia in Children

PEDIATRICS ◽  
1993 ◽  
Vol 92 (1) ◽  
pp. 78-82
Author(s):  
Richard B. Colletti ◽  
Nancy K. Roff ◽  
Ellis J. Neufeld ◽  
Annette L. Baker ◽  
Jane W. Newburger ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Total Serum ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Serum Aminotransferase ◽  
Hospital Referral

Objective. To determine the efficacy and adverse effects of niacin treatment of hypercholesterolemia in children. Design. Retrospective review. Setting. Two university hospital referral clinics. Patients. All children who received single-drug niacin treatment for severe hypercholesterolemia between 1980 and 1991. Results. Twenty-one children, aged 4 to 14 years, were treated with niacin, 500 to 2250 mg daily. Pretreatment total serum cholesterol value (mean ± SD) was 7.84 ± 1.14 mmol/L (303 ± 44 mg/dL), and low-density lipoprotein cholesterol value was 6.28 ± 1.16 mmol/L (243 ± 45 mg/dL). Niacin treatment in daily doses &gt;1000 mg reduced total cholesterol by 23% and low-density lipoprotein cholesterol by 30% (P &lt; .001) but had no effect on highdensity lipoprotein cholesterol and triglycerides. As in adults, reversible adverse effects were common, occurring in 16 (76%) of the 21 children. Six children (29%) had reversible dose-related elevations of serum aminotransferase levels. Niacin therapy was discontinued in 8 children (38%) because of flushing, abdominal pain, vomiting, headache, or elevated serum aminotransferase levels. Conclusions. This study suggests that although niacin treatment in children is efficacious, adverse effects are common. Until further study demonstrates long-term safety, niacin treatment should be reserved for the closely-supervised treatment of severe hypercholesterolemia by a lipid specialist.

scholarly journals Comparison of Friedewald’s formula, modified Friedewald’s formula and Anandaraja’s formula with direct homogenous serum LDL cholesterol method in CHD patients

2020 ◽  
Vol 8 (8) ◽  
pp. 2904
Author(s):  
Brindha Devi P. ◽  
Ilanchezhian T. ◽  
Sarguru D. ◽  
Ayyappan S. ◽  
Karnaboopathy R. ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Lipid Profile ◽  
Direct Method ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Background: Elevated serum Low-Density Lipoprotein Cholesterol (LDL-C) concentration is a well-known atherogenic risk factor with a high predictive value for coronary heart disease. An important aspect of the assessment of coronary heart disease risk for a dyslipidemic subject is the estimation of serum Low-Density Lipoprotein Cholesterol (LDL-C). There are many homogenous assays currently available for the estimation of serum LDL-C. Most clinical laboratories determine LDL-C (mg/dl) by Friedewald’s formula (FF), LD-=(TC)-HDL-C)-(TG/5), Modified Friedewald’s formula (MFF), LDL-C=(TC)-(HDL-C)-(TG/6), Recently Anandaraja and colleagues have derived a new formula for calculating LDL-C, AR-LDL-C=0.9 TC-(0.9 TG/5)-28.Methods: It is cross-sectional study. Lipid profile data was collected from known of CHD patients, who had come for lipid profile investigation to the Central Biochemistry laboratory of ACPM Medical College and hospital. LDL-C estimation was done by direct homogenous assay and also calculated using the Friedewald’s Formula, Modified Friedewald’s Formula and Anandaraja’s Formula for assessing and validity of the LDL cholesterol.Results: From the present study, The LDL-FF, MFW and AR are increased with levels of TGL > 200 mg/dl and decreased level of TC < 200 mg/dl seem to interfere with the estimation of Direct LDL cholesterolConclusions: Authors conclude that, LDL-C by direct method is most reliable and sensitive in CHD patients compare with FF, MFW, and ARF.

scholarly journals Sitosterolemia: A Rare Case with Broad Implications

2021 ◽  
Vol 4 (8) ◽  
pp. 01-05
Author(s):  
Zed Seedat
Keyword(s):  
Autosomal Recessive ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Genes Encoding ◽  
Lipid Testing ◽  
Dietary Sterols

Sitosterolemia is an ultra-rare autosomal recessive dyslipidemia characterized by mutations in genes encoding the ATP-binding cassette (ABC) G5/8 transporters. We describe the case of a 20-month-old female presenting with xanthomas and serum low density lipoprotein cholesterol of 657 mg/dL. Diagnostic workup revealed a previously undescribed sitosterolemia-causing mutation. After elimination of dietary sterols and initiation of ezetimibe therapy, the patient’s xanthomas resolved, and serum low density lipoprotein cholesterol was reduced to 104 mg/dL. Importantly, pathologically elevated serum phytosterols were found in each of the proband’s heterozygous parents. Elevated phytosterols, an established cause of atherosclerosis, are typically unrevealed by standard lipid testing. As heterozygous mutations for ABCG5/8 are relatively common, this has implications for a broader population than the ultra-rare sitosterolemia cohort. Thus, insights gleaned from this case highlight underappreciated matters in the prevention of atherosclerotic disease in both heterozygous and homozygous carriers alike.

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