Plasma lecithin:cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men

Background. Among the obese, the so-called metabolically healthy obese (MHO) phenotype is thought to confer a lower CVD risk as compared to obesity with typical associated metabolic changes. The present study aims to determine the relationship of different subtypes of obesity with inflammatory-cardiometabolic abnormalities.Methods. We evaluated 5,519 healthy, Brazilian subjects (43±10years, 78% males), free of known cardiovascular disease. Those with <2 metabolic risk factors (MRF) were considered metabolically healthy, and those with BMI ≥ 25 kg/m2and/or waist circumference meeting NCEP criteria for metabolic syndrome as overweight/obese (OW). High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and hepatic steatosis (HS) was determined via abdominal ultrasound.Results. Overall, 40% of OW individuals were metabolically healthy, and 12% normal-weight had ≥2 MRF. The prevalence of elevated CRP (≥3 mg/dL) and HS in MHO versus normal weight metabolically healthy group was 22% versus 12%, and 40% versus 8% respectively (P<0.001). Both MHO individuals and metabolically unhealthy normal weight (MUNW) phenotypes were associated with elevated hsCRP and HS.Conclusion. Our study suggests that MHO and MUNW phenotypes may not be benign and physicians should strive to treat individuals in these subgroups to reverse these conditions.

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Chosen Vascular Risk Markers in Pseudoexfoliation Syndrome: An Age-Related Disorder

Journal of Ophthalmology ◽

10.1155/2017/5231095 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Hanna Lesiewska ◽

Agnieszka Łukaszewska-Smyk ◽

Grażyna Odrowąż-Sypniewska ◽

Magdalena Krintus ◽

Aneta Mańkowska-Cyl ◽

...

Keyword(s):

Density Lipoprotein ◽

Vascular Diseases ◽

Hdl Cholesterol ◽

High Sensitivity ◽

Serum Levels ◽

Pseudoexfoliation Syndrome ◽

C Reactive Protein ◽

Related Disorder ◽

Reactive Protein ◽

Age Related

Purpose. To evaluate lipids and C-reactive protein serum levels in patients with pseudoexfoliation syndrome (PEX) in the Polish population. Methods. 96 patients were studied with PEX and 79 control subjects. Total cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, non-HDL-cholesterol and CRP serum levels, and TG/HDL-C and TC/HDL-C indexes were assessed. Results. There were no significant differences in concentration of lipids and values of TC/HDL-C, TG/HDL-C, and non-HDL-C between PEX and control groups. High-sensitivity C-reactive protein was not increased in patients with PEX. Conclusions. Our results cast doubt on the opinion on the possible PEX and vascular diseases relation. Further studies on this subject are mandatory.

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Relationship of serum homocysteine and high sensitivity C-reactive protein in elderly people with essential hypertension

International Journal of Clinical Practice ◽

10.1111/j.1742-1241.2010.02462.x ◽

2010 ◽

Vol 64 (9) ◽

pp. 1318-1319 ◽

Cited By ~ 2

Author(s):

L. Yan-Yan

Keyword(s):

Essential Hypertension ◽

Elderly People ◽

High Sensitivity ◽

C Reactive Protein ◽

Reactive Protein ◽

Serum Homocysteine ◽

Relationship Of

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Novel LCAT (Lecithin:Cholesterol Acyltransferase) Activator DS-8190a Prevents the Progression of Plaque Accumulation in Atherosclerosis Models

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.314516 ◽

2020 ◽

Author(s):

Masato Sasaki ◽

Mina Delawary ◽

Hidetaka Sakurai ◽

Hideki Kobayashi ◽

Naoki Nakao ◽

...

Keyword(s):

Small Molecule ◽

High Throughput Screening ◽

Affinity Purification ◽

Atherosclerotic Lesion ◽

Hdl Cholesterol ◽

Lecithin:Cholesterol Acyltransferase ◽

Lesion Area ◽

Acyltransferase Activity ◽

Hdl Function

Objective: Enhancement of LCAT (lecithin:cholesterol acyltransferase) activity has possibility to be beneficial for atherosclerosis. To evaluate this concept, we characterized our novel, orally administered, small-molecule LCAT activator DS-8190a, which was created from high-throughput screening and subsequent derivatization. We also focused on its mechanism of LCAT activation and the therapeutic activity with improvement of HDL (high-density lipoprotein) functionality. Approach and Results: DS-8190a activated human and cynomolgus monkey but not mouse LCAT enzymes in vitro. DS-8190a was orally administered to cynomolgus monkeys and dose dependently increased LCAT activity (ca. 2.1-fold in 3 mg/kg group on day 7), resulting in HDL cholesterol elevation without drastic changes of non-HDL cholesterol. Atheroprotective effects were then evaluated using Ldl-r KO × hLcat Tg mice fed a Western diet for 8 weeks. DS-8190a treatment achieved significant reduction of atherosclerotic lesion area (48.3% reduction in 10 mg/kg treatment group). Furthermore, we conducted reverse cholesterol transport study using Ldl-r KO × hLcat Tg mice intraperitoneally injected with J774A.1 cells loaded with [ 3 H]-cholesterol and confirmed significant increases of [ 3 H] count in plasma (1.4-fold) and feces (1.4-fold on day 2 and 1.5-fold on day3) in the DS-8190a–treated group. With regard to the molecular mechanism involved, direct binding of DS-8190a to human LCAT protein was confirmed by 2 different approaches: affinity purification by DS-8190a–immobilized beads and thermal shift assay. In addition, the candidate binding site of DS-8190a in human LCAT protein was identified by photoaffinity labeling. Conclusions: This study demonstrates the potential of DS-8190a as a novel therapeutic for atherosclerosis. This is also the first report describing that a small-molecule direct LCAT activator achieved HDL cholesterol elevation in monkey and reduction of atherosclerotic lesion area with enhanced HDL function in rodent.

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