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Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients
Aida Collado1,2, Elena Domingo1, Patrice Marques1,2
1Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain.
Insights
An oral unsaturated fat load (OUFL) improved immune parameters in primary hypercholesterolemia (PH) patients, reducing inflammation and pro-thrombotic markers. This suggests OUFL may help prevent cardiovascular events in PH.
Area of Science:
- Cardiovascular Science
- Immunology
- Nutritional Science
Background:
- Primary hypercholesterolemia (PH) involves elevated cholesterol and LDL, linked to low-grade systemic inflammation and increased cardiovascular disease (CVD) risk.
- Understanding the postprandial immune response in PH is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the effects of an oral unsaturated fat load (OUFL) on immune cell activation and function in patients with PH during the postprandial state.
- To assess changes in circulating inflammatory markers and leukocyte adhesion following OUFL administration in PH patients.
Main Methods:
- A liquid long-chain triglyceride preparation (OUFL) was given to 20 PH patients and 10 controls.
- Whole blood analysis included flow cytometry for cell activation and platelet-leukocyte aggregates, ELISA for soluble markers, and a flow chamber for leukocyte adhesion studies.
Main Results:
- PH patients showed reduced platelet and monocyte activation, and blunted neutrophil responses post-OUFL, with increased regulatory T lymphocytes.
- OUFL significantly impaired leukocyte adhesion to TNFα-stimulated endothelium in PH patients.
- Plasma levels of soluble P-selectin, PF-4/CXCL4, CXCL8, CCL2, CCL5, and TNFα were reduced post-OUFL in the PH group.
Conclusions:
- The OUFL demonstrated a beneficial effect on the pro-thrombotic and pro-inflammatory state observed in PH patients.
- OUFL may represent a promising macronutrient strategy to mitigate systemic inflammation and reduce cardiovascular event risk in PH.
Abstract:
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.
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