scholarly journals Phytosterols Supplementation Reduces Endothelin-1 Plasma Concentration in Moderately Hypercholesterolemic Individuals Independently of Their Cholesterol-Lowering Properties

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1507
Author(s):  
Angela Oliveira Godoy Ilha ◽  
Valeria Sutti Nunes ◽  
Milessa Silva Afonso ◽  
Edna Regina Nakandakare ◽  
Guilherme da Silva Ferreira ◽  
...  

Experimental and clinical studies have demonstrated the effect of phytosterols (PS) on reducing plasma levels of cholesterol and LDL-c, but the effects of plant sterols beyond cholesterol-lowering are still questionable. Since inflammation and endothelial dysfunction are involved in the pathogenesis of atherosclerosis, this study aims to evaluate the effect of PS on biomarkers involved in atherosclerosis progression and whether these effects are independent of alterations in plasma LDL-c levels. Thirty-eight moderately hypercholesterolemic volunteers (58 ± 12 years; LDL-c ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and lipid profiles and biomarkers for inflammation and endothelial dysfunction determined. The results showed that PS treatment reduced endothelin-1 plasma concentration by 11% (p = 0.02) independently of variations in plasma levels of LDL-c. No alterations were observed regarding fibrinogen, IL-6, hs-CRP, SAA, TNFα, or VCAM-1 between placebo and PS-treated groups. Furthermore, PS reduced total plasma cholesterol concentration (−5,5%, p < 0.001), LDL-c (−6.4%, p < 0.05), triglycerides (−8.3%, p < 0.05), and apo B (−5.3%, p < 0.05), without changing HDL-c concentration (p > 0.05). Therefore, PS supplementation effectively lowers endothelin-1 independently of the reductions in plasma levels of LDL-c, contributing to the comprehension of the effect of plant sterols on endothelial function and prevention of cardiovascular diseases.

2020 ◽  
Author(s):  
Valeria Sutti Nunes ◽  
Angela Oliveira Godoy Ilha ◽  
Guilherme Silva Ferreira ◽  
Renata Paula Assis Bombo ◽  
Milessa Silva Afonso ◽  
...  

Abstract Background Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol measured by the gold standard isotopic procedure we investigated whether the intestinal absorption of phytosterols (PS) depends on the body's cholesterol synthesis rate. Methods 38 volunteers (58 ± 12 years; low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and markers of phytosterol (PS) absorption and non-cholesterol sterol synthesis precursors measured. Results PS treatment reduced plasma total cholesterol concentration (-5,5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration). The lathosterol-to-cholesterol ratio in serum predicted the serum cholesterol response to PS feeding where high basal cholesterol synthesis was associated with lack of response of plasma cholesterol to PS in the diet. Cholesterol synthesis being elevated in the placebo phase in non-responders to dietary PS indicated they were resistant to further synthesis rise, whereas responders, because they have lower synthesis rate than non-responders in the placebo phase, are capable expanding synthesis under the effect of alimentary PS. Conclusions responders absorbed more PS than non-responders likely resulting from responders delivering less endogenous cholesterol than non-responders into the intestinal lumen that facilitates greater absorption of PS by the intestine.


2015 ◽  
Vol 18 (4) ◽  
pp. 344 ◽  
Author(s):  
Dhiaa A Taha ◽  
Ellen K Wasan ◽  
Kishor M Wasan ◽  
Pavel Gershkovich

Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


1989 ◽  
Vol 17 (4) ◽  
pp. 388-394 ◽  
Author(s):  
G. Mastroberardino ◽  
C. Costa ◽  
M.S. Gavelli ◽  
E. Vitaliano ◽  
F. Rossi ◽  
...  

Plasma testosterone and cortisol concentrations were measured in 32 familial heterozygous hypercholesterolaemic subjects, aged 40 – 45 years. The subjects were divided into two groups of 16, each containing eight men and eight women. The women had normal menstrual cycles. After a period on placebo, one group of patients was given 40 mg/day lovastatin and the other was given 1500 mg/day clofibrate. Both drugs significantly reduced the plasma cholesterol concentration, however, unlike clofibrate, lovastatin did not decrease plasma levels of testosterone and cortisol. The response to stimulation by adrenocorticotrophic hormone of plasma cortisol and urinary 17-hydroxy levels was significantly reduced by treatment with clofibrate, but unchanged by lovastatin. The different effects produced by the two drugs probably reflect different mechanisms and sites of action.


2007 ◽  
Vol 98 (5) ◽  
pp. 890-899 ◽  
Author(s):  
Christiane B. Fricke ◽  
Malene Schrøder ◽  
Morten Poulsen ◽  
Klaus von Bergmann ◽  
Ingmar Wester ◽  
...  

Foods containing plant sterol or stanol esters can be beneficial in lowering LDL-cholesterol concentration, a major risk factor for CVD. The present study examined whether high dietary intake of rapeseed oil (RSO) derived plant sterol and stanol esters is associated with increased levels of these components in brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for familial hypercholesterolemia. Homozygous animals received either a standard diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally fed with 2 g cholesterol/kg to the respective diet form for 120 d (n 9 for each group). Concentrations of cholesterol, its precursor lathosterol, plant sterols and stanols in brain and additionally in liver and plasma were determined by highly sensitive GC–MS. High-dose intake of RSO derived plant sterols and stanols resulted in increased levels of these components in plasma and liver. In brain a limited uptake of plant sterols and stanols was proven, indicating that these compounds passed the blood–brain barrier and may be retained in the brain tissue of Watanabe rabbits. Plant stanol ester feeding lowered plant sterol levels in brain, liver, and plasma. Cholesterol synthesis in brain, indicated by lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be affected by plant sterol or stanol ester feeding. We conclude that high dose intake of plant sterol and stanol esters in Watanabe rabbits results in elevated concentrations of these components not only in the periphery but also in the central nervous system.


1973 ◽  
Vol 45 (3) ◽  
pp. 313-329 ◽  
Author(s):  
D. Reichl ◽  
L. A. Simons ◽  
N. B. Myant ◽  
J. J. Pflug ◽  
G. L. Mills

1. The lipids and lipoproteins of lymph obtained from the dorsum of the foot were examined in seven human subjects. 2. The concentration of total cholesterol in lymph was about one-tenth that in plasma and was significantly correlated with the plasma total cholesterol concentration. The ratio of esterified to total cholesterol in lymph was similar to that in plasma. 3. Triglyceride was detectable in lymph, but the concentration was less than one-tenth that in plasma and was unrelated to the plasma triglyceride concentration. 4. No lipase activity was detectable in lymph, either before or after intravenous injection of heparin. 5. Cholesterol-esterifying activity was detected in four samples of lymph. 6. The major lipoprotein antigens of human plasma (apo-A, apo-B and apo-C) were present in whole lymph, but their distribution in fractions of different density was different from that in plasma. 7. [14C]Cholesterol, injected intravenously, appeared in lymph within 30 min of the injection, indicating that some of the cholesterol in lymph is derived directly from plasma. 8. At intervals greater than 29 days after a single intravenous injection of [14C]-cholesterol, the specific radioactivity of lymph cholesterol was greater than that of plasma cholesterol, indicating that some of the cholesterol in lymph is derived from tissue pools of cholesterol with slow turnover.


Life Sciences ◽  
2012 ◽  
Vol 91 (13-14) ◽  
pp. 699-702 ◽  
Author(s):  
Mauro Cellini ◽  
Ernesto Strobbe ◽  
Corrado Gizzi ◽  
Nicole Balducci ◽  
Pier Giorgio Toschi ◽  
...  

2016 ◽  
Vol 23 (3) ◽  
Author(s):  
Hanna O Palahniuk

Despite overall effort hypertensive disease (HD) is one of the most significant health and social problem. Essential hypertension is believed to be a multifactorial disease and polymorphism of genes that may be responsible for the regulation of blood pressure plays the key role in it. The least explored in this regard is single nucleotide polymorphism of ET-1 leading to the replacement of the amino acids of lysine (Lys) to asparagine (Asn) at position of 198th polypeptide chain (Lys198Asn).The objective of the research was to improve diagnosis of HD severity determining plasma concentration of ET-1, C-type natriuretic peptides (CNP) and the coefficient of CNP/ET-1 in patients with different genotypes of ET-1 gene.Materials and methods. The study involved 79 men without cardiovascular diseases (control group), 62 men with II stage HD and 50 men with HD complicated by chronic heart failure (CHF) II-III classes according to NYHA Classification. All patients were representative by age. Genotyping of ET-1 gene was conducted using polymerase chain reaction. ET-1 concentration in plasma was determined using ELISA method.Results. Lys/Lys genotype of ET-1 gene was found to occur in 65.82% of men in the control group, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) constituted 34.18%, Lys allele was observed in 79.75% of cases, Asn allele was detected in 20.25% of men. Among patients with II stage HD Lys/Lys genotype of ET-1 gene was observed in 56.45% of cases, the carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) occurred in 43.55% of patients, Lys allele was found in 73.39% of cases, Asn allele was observed in 26.61% of patients. Among men with HD and CHF IIA genotype Lys/Lys was found in 66.00% of cases, carriers of Asn allele (Lys/Asn and Asn/Asn genotypes) was observed in 34.00% of patients, Lys allele was detected in 80.00% of cases, Asn allele was observed in 20.00% of cases. The men from the control group, patients with II stage HD and patients with HD and CHF as the carriers of Asn allele were found to have significantly higher plasma levels of ET-1 (2.53±0.12 fmol/ml, 13.90±0.22 fmol/ml and 14.07±0.18 fmol/ml, respectively) and CNP (2.98±0.08 pmol/ml, 5.90±0.11 pmol/ml and 5.93±0.18 pmol/ml, respectively) in comparison with homozygous carriers of Lys genotype (ET-1constituted 1.41±0.05 fmol/ml, 11.58±0.23 fmol/ml and 0.08±12.89 fmol/ml, respectively, CNP constituted 2.02±0.29 pmol/ml, 4.68±0.12 pmol/ml and 4.88±0.09 pmol/ml, respectively). According to the analysis of the obtained data, coefficient of CNP/ET-1 (0.40±0.003 c.u. and 0.38±0.006 c.u., respectively) and Asn allele (0.42±0.004 c.u. and 0.42±0.007 c.u., respectively) was significantly lower in patients with II stage HD and patients with HD and CHF as the carriers of Lys/Lys genotype in comparison with the control group (1.4±0.04 c.u. and 1.22±0.05 c.u., respectively). Carriers of Asn allele in the control group had significantly lower coefficient of CNP/ET-1 than genotype Lys/Lys carriers. However, the difference in the coefficient of CNP/ET-1 was not observed in patients with HD.Conclusions. Lys/Lys genotype and Lys allele of ET-1 gene were found to dominate among control group and patients with HD of different severity. Plasma concentration of ET-1, CNP were significantly higher and coefficient of CNP/ET-1 was lower in men with II stage HD and HD complicated by CHF than in men without cardiovascular diseases in case of all ET-1 gene genotypes. The carriers of Asn allele of ET-1 gene had significantly higher plasma levels of ET-1 and CNP in each study group.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4826-4826
Author(s):  
Francine Chenou ◽  
Bidossessi Wilfried Hounkpe ◽  
Igor de Farias Domingos ◽  
Thais Helena Chaves Batista ◽  
Rodrigo Marcionilo Santana ◽  
...  

Background: Sickle cell anemia (SCA) is characterized by chronic hemolysis and endothelial dysfunction (ED). Plasma hemoglobin (pHb) and its heme component released from intravascular hemolysis (IH) are among the most important factors contributing to ED. Unfortunately, the importance of IH to the development of an ED and the effects of hydroxyurea therapy on IH and ED in SCA remains unclear. Aims: We evaluated plasma levels of IH and ED markers among Brazilian SCA patients not receiving hydroxyurea therapy (HbSS), and compared with those of hydroxyurea-treated SCA patients (HbSS_HU) and healthy controls (HbAA). Methods: A cross-sectional study of 60 SCA consenting patients (32 HbSS and 28 HbSS_HU; 19-42 years) in steady state, who are being followed up at the Blood Center, Pernambuco (HEMOPE) and 32 HbAA controls. The IH markers were serum Lactate Dehydrogenase [LDH] and total heme measured by enzymatic colorimetric tests, and pHb measured by enzyme-linked immunosorbent assay (ELISA). The ED markers were plasma von Willebrand factor (vWF:Ag) and vWF ristocetin cofactor activity (vWF:Rco) levels measured by the latex enhanced immunoassay. The other ED markers were the antigen of vWF-cleaving protease (ADAMTS13:Ag), thrombospondin-1 and endothelin-1 levels measured by ELISA, and ADAMTS13 Activity (ADAMTS13:Act) measured by FRETS-VWF73 method. The study was approved by the Ethics Committee of the State University of Campinas and HEMOPE under protocol No: 1.863.428. Data were analyzed using GraphPad Prism 6. Results: The pHb and LDH were significantly increased in HbSS than HbSS_HU patients (Figures 1A and 1B). Plasma levels of vWF:Ag, vWF:Rco, serum levels of total heme, thrombospondin-1 and endothelin-1 were significantly increased in HbSS and HbSS_HU patients compared to HbAA controls (Figures 1C and 2A, 2B, 2E, 2F), while serum level of thrombospondin-1 level was elevated in HbSS than HbSS_HU patients (Figure 2E). Similarly, ADAMTS13:Ag levels and ADAMTS13 activity were significantly lower in HbSS and HbSS_HU patients than HbAA controls, while ADAMTS13 activity levels were significantly elevated in HbSS_HU patients compared to HbSS patients (Figure 2D). In HbSS_HU patients, the ADAMTS13:Act was negatively correlated with heme and LDH [r = -0.47, p = 0.013; and r = -0.44, p = 0.023 respectively]. In additional, heme was positively correlated with vWF:Ag and LDH [(r = 0.47, p = 0.017) and (r = 0.56, p = 0.003) respectively]. In HbSS patients, LDH and pHb were positively correlated (r = 0.44, p = 0.014). Conclusions: Hydroxyurea therapy was associated with a reduced levels of LDH, pHb and thrombospondin-1 levels, and increased levels of ADAMTS13 activity in SCA patients. Increased ADAMTS13 activity levels may be attributed to reduction of pHb and thrombospondin-1 levels because previous invitro studies have shown that thrombospondin-1 or pHb are bound to vWF. Thus, vWF is restrained from ADAMTS13 activity and cleavage, and hyperreactive vWF might accumulate as a consequence of inhibition of ADAMTS13 activity. Increased thrombospondin-1, pHb and hyperreactive vWF levels are proposed to participate in sickle cell adhesion and promote thrombotic complications. Therefore, our results demonstrate an additional clinical benefit for the use of hydroxyurea in these patients. Disclosures No relevant conflicts of interest to declare.


2003 ◽  
Vol 2 (1) ◽  
pp. 127
Author(s):  
S DELRY ◽  
C PASSINO ◽  
M MALTINTI ◽  
J KHABIRINEJAD ◽  
M EMDIN ◽  
...  

1981 ◽  
Vol 97 (1) ◽  
pp. 91-97 ◽  
Author(s):  
H. Storm ◽  
C. van Hardeveld ◽  
A. A. H. Kassenaar

Abstract. Basal plasma levels for adrenalin (A), noradrenalin (NA), l-triiodothyronine (T3), and l-thyroxine (T4) were determined in rats with a chronically inserted catheter. The experiments described in this report were started 3 days after the surgical procedure when T3 and T4 levels had returned to normal. Basal levels for the catecholamines were reached already 4 h after the operation. The T3/T4 ratio in plasma was significantly increased after 3, 7, and 14 days in rats kept at 4°C and the same holds for the iodide in the 24-h urine after 7 and 14 days at 4°C. The venous NA plasma concentration was increased 6- to 12-fold during the same period of exposure to cold, whereas the A concentration remained at the basal level. During infusion of NA at 23°C the T3/T4 ratio in plasma was significantly increased after 7 days compared to pair-fed controls, and the same holds for the iodide excretion in the 24-h urine. This paper presents further evidence for a role of the sympathetic nervous system on T4 metabolism in rats at resting conditions.


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