Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis.

Mohammad A Alfhili,Ghadeer S Aljuraiban

doi:10.3390/cells10123388

Abstract

Cardiovascular diseases (CVD) are a leading cause of mortality worldwide, and dietary habits represent a major risk factor for dyslipidemia; a hallmark of CVD. Saturated fatty acids contribute to CVD by aggravating dyslipidemia, and, in particular, lauric acid (LA) raises circulating cholesterol levels. The role of red blood cells (RBCs) in CVD is increasingly being appreciated, and eryptosis has recently been identified as a novel mechanism in CVD. However, the effect of LA on RBC physiology has not been thoroughly investigated. RBCs were isolated from heparin-anticoagulated whole blood (WB) and exposed to 50–250 μM of LA for 24 h at 37 °C. Hemoglobin was photometrically examined as an indicator of hemolysis, whereas eryptosis was assessed by Annexin V-FITC for phosphatidylserine (PS) exposure, Fluo4/AM for Ca2+, light scatter for cellular morphology, H2DCFDA for oxidative stress, and BODIPY 581/591 C11 for lipid peroxidation. WB was also examined for RBC, leukocyte, and platelet viability and indices. LA caused dose-responsive hemolysis, and Ca2+-dependent PS exposure, elevated erythrocyte sedimentation rate (ESR), cytosolic Ca2+ overload, cell shrinkage and granularity, oxidative stress, accumulation of lipid peroxides, and stimulation of casein kinase 1α (CK1α). In WB, LA disrupted leukocyte distribution with elevated neutrophil-lymphocyte ratio (NLR) due to selective toxicity to lymphocytes. In conclusion, this report provides the first evidence of the pro-eryptotic potential of LA and associated mechanisms, which informs dietary interventions aimed at CVD prevention and management.

Highlights

Cardiovascular diseases (CVD) are a leading cause of mortality and disability worldwide [1]
The basis for guidelines suggesting reduced intakes of saturated fatty acids provides evidence of their contribution to dyslipidemia as fatty acids (FAs) in the diet are hydrolyzed into free fatty acids (FFAs) [4]; circulating in the bloodstream and acting as an energy source for organs and regulating cellular function [5], including lymphocyte proliferation [6], activation by antigens [7], and stimulation of cell death [8,9], among others [10]
Hemolysis exacerbates oxidative injury associated with CVD

Summary

Introduction

Cardiovascular diseases (CVD) are a leading cause of mortality and disability worldwide [1]. The number of cases of CVD doubled over the past three decades to 523 million cases in 2019, contributing to 18.6 million deaths that same year [1]. These figures correspond to 34.4 million years lived with disability [1]. To address this issue, implementing strategies to deal with underlying contributors to CVD, such as hypertension, hyperglycemia, inflammation, obesity, and dyslipidemia, can have major health benefits [1]. It is suspected that FFAs contribute to the risk of non-communicable diseases, for instance, higher levels of FFAs have been associated with sudden cardiac death [11], heart failure [12], and diabetes [13]

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