scholarly journals The Differential Effects of HDL Subpopulations on Lipoprotein Lipase (LPL)-Mediated VLDL Catabolism

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1839
Author(s):  
Ewa Wieczorek ◽  
Agnieszka Ćwiklińska ◽  
Agnieszka Kuchta ◽  
Barbara Kortas-Stempak ◽  
Anna Gliwińska ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Electrophoretic Mobility ◽  
Free Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Ratio ◽  
Atherosclerosis Progression ◽  
Low Hdl ◽  
Vldl Remnant ◽  
The Impact

High-density lipoprotein (HDL) subpopulations functional assessment is more relevant for HDL anti-atherogenic activity than cholesterol level. The aim of the study was to assess the impact of HDL-2 and HDL-3 on lipoprotein lipase (LPL)-mediated very-low-density lipoprotein (VLDL) catabolism related to hypertriglyceridemia development. VLDL and HDLs were isolated from serum by ultracentrifugation. VLDL was incubated with LPL in the absence and presence of total HDL or HDL subpopulations. Next, VLDL remnants were separated, and their composition and electrophoretic mobility was assessed. Both HDL subpopulations increased the efficiency of triglyceride lipolysis and apolipoprotein CII and CIII removal from VLDL up to ~90%. HDL-3 exerted significantly greater impact than HDL-2 on apolipoprotein E (43% vs. 18%, p < 0.001), free cholesterol (26% vs. 18%, p < 0.05) and phospholipids (53% vs. 43%, p < 0.05) removal from VLDL and VLDL remnant electrophoretic mobility (0.18 vs. 0.20, p < 0.01). A greater release of these components was also observed in the presence of total HDL with a low HDL-2/HDL-3 cholesterol ratio. Both HDL subpopulations affect VLDL composition during lipolysis, but HDL-3 exhibited a greater effect on this process. Altered composition of HDL related to significant changes in the distribution between HDL-2 and HDL-3 can influence the VLDL remnant features, affecting atherosclerosis progression.

scholarly journals Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease

2019 ◽  
Vol 27 (15) ◽  
pp. 1606-1616 ◽  
Author(s):  
Ma Feng ◽  
Maryam Darabi ◽  
Emilie Tubeuf ◽  
Aurélie Canicio ◽  
Marie Lhomme ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
High Density Lipoprotein ◽  
Lipoprotein Lipase ◽  
Free Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Knock Out ◽  
Low Hdl

Background Low concentrations of high-density lipoprotein cholesterol (HDL-C) represent a well-established cardiovascular risk factor. Paradoxically, extremely high HDL-C levels are equally associated with elevated cardiovascular risk, resulting in the U-shape relationship of HDL-C with cardiovascular disease. Mechanisms underlying this association are presently unknown. We hypothesised that the capacity of high-density lipoprotein (HDL) to acquire free cholesterol upon triglyceride-rich lipoprotein (TGRL) lipolysis by lipoprotein lipase underlies the non-linear relationship between HDL-C and cardiovascular risk. Methods To assess our hypothesis, we developed a novel assay to evaluate the capacity of HDL to acquire free cholesterol (as fluorescent TopFluor® cholesterol) from TGRL upon in vitro lipolysis by lipoprotein lipase. Results When the assay was applied to several populations markedly differing in plasma HDL-C levels, transfer of free cholesterol was significantly decreased in low HDL-C patients with acute myocardial infarction (−45%) and type 2 diabetes (–25%), and in subjects with extremely high HDL-C of >2.59 mmol/L (>100 mg/dL) (−20%) versus healthy normolipidaemic controls. When these data were combined and plotted against HDL-C concentrations, an inverse U-shape relationship was observed. Consistent with these findings, animal studies revealed that the capacity of HDL to acquire cholesterol upon lipolysis was reduced in low HDL-C apolipoprotein A-I knock-out mice and was negatively correlated with aortic accumulation of [3H]-cholesterol after oral gavage, attesting this functional characteristic as a negative metric of postprandial atherosclerosis. Conclusions Free cholesterol transfer to HDL upon TGRL lipolysis may underlie the U-shape relationship between HDL-C and cardiovascular disease, linking HDL-C to triglyceride metabolism and atherosclerosis.

scholarly journals Psoriasis and Cardiovascular Risk—Do Promising New Biomarkers Have Clinical Impact?

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sirje Kaur ◽  
Külli Kingo ◽  
Mihkel Zilmer
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Epidemiological Studies ◽  
Overweight And Obesity ◽  
Biologically Active ◽  
Cvd Risk ◽  
Low Hdl ◽  
New Biomarkers ◽  
The Impact

Epidemiological studies suggest an increased prevalence of cardiovascular disease (CVD) in patients with psoriasis (PS). Therefore, emphasis has lately been laid on the necessity for clinical evaluation of the risk of CVD in these patients. The systemic inflammatory markers C-reactive protein (CRP) and interleukin- (IL-) 6, which have long been used to predict future CVD in the general population, are increased manyfold in patients with PS. Lipid abnormalities characterized by elevated triglycerides, low HDL cholesterol, and higher concentrations of LDL cholesterol and its oxidized form are also prevalent in patients. There is a need for additional laboratory markers for the assessment of cardiovascular status of patients with PS. Due to frequent comorbid overweight and obesity, biologically active compounds produced by adipocytes may have an impact on monitoring the status of the cardiovascular system of patients with PS. For this purpose, two adipokines, adiponectin and leptin, have been most extensively studied. The review focuses on some inflammatory and oxidative stress aspects in patients with PS through the analysis of the impact of prominent adipokines and oxidized low-density lipoprotein (oxLDL) to assess their eligibility for clinical practice as markers of CVD risk in patients with PS.

scholarly journals Prediction of Cardiorespiratory Fitness in Czech Adults: Normative Values and Association with Cardiometabolic Health

2021 ◽  
Author(s):  
Geraldo A. Maranhao Neto ◽  
Iuliia Pavlovska ◽  
Anna Polcrova ◽  
Jeffrey Mechanick ◽  
Maria Infante-Garcia ◽  
...  
Keyword(s):  
Cardiorespiratory Fitness ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Normative Values ◽  
Cardiometabolic Health ◽  
Inverse Association ◽  
Low Hdl ◽  
The Impact ◽  
Strong Independent Predictor

Cardiorespiratory fitness (CRF) is a strong independent predictor of morbidity and mortality. However, there is no recent information about the impact of CRF on cardiometabolic risk specifically in Central and Eastern Europe, which are characterized by different biological and social determinants of health. Normative CRF values were proposed and the association between CRF and cardiometabolic outcomes was evaluated in an adult Czechian population. In 2054 participants (54.6 % females, median 48 years), the CRF was predicted from a non-exercise equation. Multivariable-adjusted logistic regressions were carried out to determine the associations. Higher CRF quartiles were associated with lower prevalence of hypertension, type 2 diabetes (T2D) and dyslipidaemia. Comparing subjects within the lowest CRF, those within the highest CRF had decreased chances of hypertension (odds ratio [OR] = 0.36; 95% CI: 0.22-0.60); T2D (OR=0.16; 95% CI 0.05-0.47), low HDL-c (OR=0.32; 95% CI 0.17-0.60), high low-density lipoprotein (OR=0.33; 95% CI 0.21-0.53), high triglycerides (OR=0.13; 95 CI 0.07-0.81), and high cholesterol (OR=0.44; 95% CI 0.29-0.69). There was an inverse association between CRF and cardiometabolic outcomes, supporting the adoption of a non-exercise method to estimate CRF of the Czech population. Therefore, more accurate cardiometabolic studies can be performed incorporating the valuable CRF metric.

scholarly journals Prediction of Cardiorespiratory Fitness in Czech Adults: Normative Values and Association with Cardiometabolic Health

2021 ◽  
Vol 18 (19) ◽  
pp. 10251
Author(s):  
Geraldo A. Maranhao Neto ◽  
Iuliia Pavlovska ◽  
Anna Polcrova ◽  
Jeffrey I. Mechanick ◽  
Maria M. Infante-Garcia ◽  
...  
Keyword(s):  
Cardiorespiratory Fitness ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cross Sectional Study ◽  
Normative Values ◽  
Cardiometabolic Health ◽  
Inverse Association ◽  
Cross Sectional ◽  
Low Hdl ◽  
The Impact

Cardiorespiratory fitness (CRF) is a strong independent predictor of morbidity and mortality. However, there is no recent information about the impact of CRF on cardiometabolic risk specifically in Central and Eastern Europe, which are characterized by different biological and social determinants of health. In this cross-sectional study normative CRF values were proposed and the association between CRF and cardiometabolic outcomes was evaluated in an adult Czechian population. In 2054 participants (54.6% females), median age 48 (IQR 19 years), the CRF was predicted from a non-exercise equation. Multivariable-adjusted logistic regressions were carried out to determine the associations. Higher CRF quartiles were associated with lower prevalence of hypertension, type 2 diabetes (T2D) and dyslipidemia. Comparing subjects within the lowest CRF, we see that those within the highest CRF had decreased chances of hypertension (odds ratio (OR) = 0.36; 95% CI: 0.22–0.60); T2D (OR = 0.16; 0.05–0.47), low HDL-c (OR = 0.32; 0.17–0.60), high low-density lipoprotein (OR = 0.33; 0.21–0.53), high triglycerides (OR = 0.13; 0.07–0.81), and high cholesterol (OR = 0.44; 0.29–0.69). There was an inverse association between CRF and cardiometabolic outcomes, supporting the adoption of a non-exercise method to estimate CRF of the Czech population. Therefore, more accurate cardiometabolic studies can be performed incorporating the valuable CRF metric.

Epidemiology Of Myocardial Infarction: Magnitude Of The Problem, Cause And Risk Factors

1981 ◽  
Author(s):  
W B Kannel
Keyword(s):  
Risk Factors ◽  
Risk Evaluation ◽  
Death Rate ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Joint Effect ◽  
Low Density Lipoprotein Cholesterol ◽  
The Impact ◽  
Marginal Risk

Coronary heart disease is a common, highly lethal, disease which frequently attacks without warning and too often presents with sudden death as the first symptom. Chances of an American male developing CHD before age 60 are one in five.Most angina, infarctions and sudden deaths represent medical failures which should have been forecasted and prevented. About 30% of first MI's will shortly develop angina and experience a per annum death rate, half of which will be sudden deaths. Reinfarctions will occur at 6% per year and half the recurrences will be fatal.No major innovations are needed to identify coronary candidates or to establish their risk from the joint effect of known risk factors. However, all have much to learn about motivating changes in behavior required to control the major risk factors such as cigarette smoking, faulty diet, overweight, sedentary living, abnormal lipids, hypertension and impaired glucose tolerance.Low density lipoprotein cholesterol promotes atherogenesis whereas HDL-cholesterol is protective, and the net effect is judged by their ratio. Hypertension, systolic or diastolic, labile or fixed, at any age in either sex is a powerful contributor to CHD. The impact of diabetes is greater for women, diminishes with age and varies depending on coexisting risk factors.Optimal risk evaluation requires quantitative combination of risk factors so as to include persons with multiple marginal risk factor abnormalities who are at high risk.

scholarly journals Identification of 31 novel mutations in the F8 gene in Spanish hemophilia A patients: structural analysis of 20 missense mutations suggests new intermolecular binding sites

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3468-3478 ◽  
Author(s):  
Adoración Venceslá ◽  
María Ángeles Corral-Rodríguez ◽  
Manel Baena ◽  
Mónica Cornet ◽  
Montserrat Domènech ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Missense Mutations ◽  
Factor X ◽  
Novel Mutations ◽  
Large Deletions ◽  
Function Relationship ◽  
The Impact

Abstract Hemophilia A (HA) is an X-linked bleeding disorder caused by a wide variety of mutations in the factor 8 (F8) gene, leading to absent or deficient factor VIII (FVIII). We analyzed the F8 gene of 267 unrelated Spanish patients with HA. After excluding patients with the common intron-1 and intron-22 inversions and large deletions, we detected 137 individuals with small mutations, 31 of which had not been reported previously. Eleven of these were nonsense, frameshift, and splicing mutations, whereas 20 were missense changes. We assessed the impact of the 20 substitutions based on currently available information about FV and FVIII structure and function relationship, including previously reported results of replacements at these and topologically equivalent positions. Although most changes are likely to cause gross structural perturbations and concomitant cofactor instability, p.Ala375Ser is predicted to affect cofactor activation. Finally, 3 further mutations (p.Pro64Arg, p.Gly494Val, and p.Asp2267Gly) appear to affect cofactor interactions with its carrier protein, von Willebrand factor, with the scavenger receptor low-density lipoprotein receptor–related protein (LRP), and/or with the substrate of the FVIIIapi•FIXa (Xase) complex, factor X. Characterization of these novel mutations is important for adequate genetic counseling in HA families, but also contributes to a better understanding of FVIII structure-function relationship.

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