scholarly journals Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Aida Collado ◽  
Elena Domingo ◽  
Patrice Marques ◽  
Eva Perello ◽  
Sergio Martínez-Hervás ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Leukocyte Adhesion ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lower Percentage ◽  
Low Grade ◽  
Platelet Factor ◽  
Primary Hypercholesterolemia ◽  
Unsaturated Fat ◽  
Postprandial State

Context: Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting.Objective: To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state.Design: A commercial liquid preparation of long-chain triglycerides (Supracal®; ω6/ω3 ratio >20/1, OUFL) was administered to 20 patients and 10 age-matched controls. Whole blood was collected before (fasting state) and 4 h after administration (postprandial state). Flow cytometry was employed to determine platelet and leukocyte activation, and the levels of circulating platelet-leukocyte aggregates. Soluble markers were determined by ELISA, and the parallel-plate flow chamber was employed to study leukocyte adhesion to the dysfunctional arterial endothelium.Results: The PH group had a lower percentage of activated platelets and circulating type 1 monocytes, and blunted neutrophil activation after the OUFL, accompanied by a significant increase in the percentage of regulatory T lymphocytes. In this group, the OUFL led to a significant impairment of leukocyte adhesion to the dysfunctional [tumor necrosis factor α (TNFα)-stimulated] endothelium and reduced the plasma levels of soluble P-selectin, platelet factor-4 (PF-4)/CXCL4, CXCL8, CCL2, CCL5, and TNFα.Conclusion: The OUFL has a beneficial impact on the pro-thrombotic and pro-inflammatory state of PH patients and might be a promising macronutrient approach to dampen the systemic inflammation associated with PH and the development of further cardiovascular events.

scholarly journals Regulation of low-density lipoprotein cholesterol by intestinal inflammation and the acute phase response

2017 ◽  
Vol 114 (2) ◽  
pp. 226-232 ◽  
Author(s):  
Karl E Herbert ◽  
Clett Erridge
Keyword(s):  
Systemic Inflammation ◽  
Intestinal Inflammation ◽  
Mammalian Species ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
High Dose ◽  
Low Grade ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

AbstractSystemic inflammation, induced by disease or experimental intervention, is well established to result in elevated levels of circulating triglycerides, and reduced levels of high-density lipoprotein-cholesterol (HDL-C), in most mammalian species. However, the relationship between inflammation and low-density lipoprotein-cholesterol (LDL-C) concentrations is less clear. Most reports indicate that systemic inflammation, as observed during sepsis or following high dose experimental endotoxaemia, lowers total, and LDL-C in man. However, isolated reports have suggested that certain inflammatory conditions are associated with increased LDL-C. In this review, we summarize the emerging evidence that low-grade inflammation specifically of intestinal origin may be associated with increased serum LDL-C levels. Preliminary insights into potential mechanisms that may mediate these effects, including those connecting inflammation to trans-intestinal cholesterol efflux (TICE), are considered. We conclude that this evidence supports the potential downregulation of major mediators of TICE by inflammatory mediators in vitro and during intestinal inflammation in vivo. The TICE-inflammation axis therefore merits further study in terms of its potential to regulate serum LDL-C, and as a readily druggable target for hypercholesterolaemia.

scholarly journals Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation

2018 ◽  
Vol 8 (1) ◽  
pp. 18
Author(s):  
Aida Collado ◽  
Patrice Marques ◽  
Elena Domingo ◽  
Eva Perello ◽  
Herminia González-Navarro ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Immune Cell ◽  
Leukocyte Adhesion ◽  
Flow Chamber ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
Leukocyte Activation ◽  
Primary Hypercholesterolemia ◽  
Th17 Lymphocytes ◽  
Arterial Endothelium

Primary hypercholesterolemia (PH) is associated with a low grade systemic inflammation that is likely the main driver of premature atherosclerosis. Accordingly, we characterized the immune cell behaviour in PH and its potential consequences. Whole blood from 22 PH patients and 21 age-matched controls was analysed by flow cytometry to determine the percentage of leukocyte immunophenotypes, activation, and platelet-leukocyte aggregates. Plasma markers were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The adhesion of platelet-leukocyte aggregates to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium was investigated using the dynamic model of the parallel-plate flow chamber. PH patients presented greater percentage of Mon 3 monocytes, Th2 and Th17 lymphocytes, activated platelets, and leukocytes than controls. The higher percentages of circulating platelet-neutrophil, monocyte and lymphocyte aggregates in patients caused increased platelet-leukocyte adhesion to dysfunctional arterial endothelium. Circulating CXCL8, CCL2, CX3CL1, and IL-6 levels positively correlated with key lipid features of PH, whereas negative correlations were found for IL-4 and IL-10. We provide the first evidence that increased platelet and leukocyte activation leads to elevated platelet-leukocyte aggregates in PH and augmented arterial leukocyte adhesiveness, a key event in atherogenesis. Accordingly, modulation of immune system behavior might be a powerful target in the control of further cardiovascular disease in PH.

scholarly journals Reduction of Vascular Inflammation, LDL-C, or Both for the Protection from Cardiovascular Events?

2018 ◽  
Vol 12 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Andromachi Reklou ◽  
Michael Doumas ◽  
Konstantinos Imprialos ◽  
Konstantinos Stavropoulos ◽  
Dimitris Patoulias ◽  
...  
Keyword(s):  
Vascular Inflammation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Myocardial Damage ◽  
Lipid Lowering ◽  
Human Antibody ◽  
Low Grade ◽  
Cvd Risk ◽  
Expensive Drug ◽  
Arterial Inflammation

Background: Low density lipoprotein cholesterol (LDL-C) and low grade arterial inflammation are key pathogenic factors for atherosclerosis and its manifestation, cardiovascular disease (CVD). Objective: In this narrative review we assessed if decreasing LDL-C levels or inflammation or both is more effective in reducing CVD events. Results: In the Scandinavian Simvastatin Survival Study (4S), all statin trials of the 90s’ and the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) the benefit came from the LDL-C reduction. In the GREak and Atorvastatin Coronary heart disease Evaluation (GREACE), the Treating to New Targets (TNT), and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials both mechanisms in combination produced significant benefits. In the Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trials and the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) with a human antibody targeting IL-1β with no lipid lowering effect, the reduction in arterial inflammation played the only beneficial role because there was no change in lipids levels. Conclusion: Both LDL-C and inflammation reduction are beneficial to the reduction of CVD risk. However, canakinumab is a very expensive drug that only induced a 15% reduction in CVD events, thus drastically reducing the possibility for it to be used in clinical practice. Besides, canakinumab is associated with increased infections, some fatal. A potent statin with anti-inflammatory effects is probably the best choice for the majority of those needing hypolipidaemic drug therapy.

scholarly journals KORELASI KADAR HIGH SENSITIVITY C-REACTIVE PROTEIN DENGAN KADAR LOW DENSITY LIPOPROTEIN PADA PENYANDANG OBES

2020 ◽  
Vol 5 (3) ◽  
pp. 676
Author(s):  
Rama Dhanivita Djamin
Keyword(s):  
Interleukin 1 ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Low Grade ◽  
Low Density ◽  
C Reactive Protein ◽  
Necrosis Factor Alpha ◽  
Reactive Protein ◽  
Hs Crp

<p><em>Obesitas terjadi karena akumulasi lemak berlebih di dalam tubuh. Akumulasi lemak menimbulkan low grade inflammation pada jaringan adiposa, menyebabkan peningkatan sitokin inflamasi seperti tumor necrosis factor-alpha, interleukin-1 beta, dan interleukin-6 (IL-6). Peningkatan sekresi IL-6 merangsang hepar meningkatkan produksi protein fase akut. High sensitivity C-reactive protein (hs-CRP) sebagai penanda inflamasi merupakan protein fase akut. Low density lipoprotein (LDL-kolesterol) adalah lipoprotein yang paling banyak mengandung kolesterol. Peningkatan kadar hs-CRP dan kadar LDL-kolesterol pada obesitas diidentifikasi sebagai faktor risiko aterosklerosis. Penelitian ini bertujuan menganalisis hubungan hs-CRP dengan LDL-kolesterol pada penyandang obes, merupakan penelitian analitik rancangan potong lintang dilakukan  September 2018 sampai Agustus 2019. Kadar hs-CRP diperiksa dengan metode enzyme linked immunoassay (ELISA), sedangkan kadar LDL-kolesterol dengan metode kalkulasi (rumus Friedewald). Uji korelasi Spearman digunakan untuk menganalisi data, jika didapatkan nilai p&lt;0,05 korelasi dinyatakan bermakna. Subjek penelitian berjumlah 26 penyandang obes terdiri dari 6 laki-laki (23,1%) dan 20 perempuan (76,9%). Rerata umur subjek penelitian adalah 36,46(7,68) tahun. Rerata kadar hs-CRP dan kadar LDL-kolesterol adalah 5,08(1,28) mg/L dan  154,69(45,8) mg/dL. Analisis korelasi menunjukkan korelasi positif lemah dan tidak bermakna secara statistik antara kadar hs-CRP dengan kadar LDL-kolesterol (r= 0,333, p=0,096). Simpulan: Terdapat korelasi positif lemah antara kadar hs-CRP dengan kadar LDL-kolesterol pada penyandang obes.</em></p><p><strong><em>Kata kunci</em></strong><em>: </em><em>Obesitas, High Sensitivity C-Reactive, Low Density Lipoprotein</em><em></em></p>

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