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

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.

 

Comments:

The study you described highlights the potential impact of lauric acid (LA), a type of saturated fatty acid, on red blood cells (RBCs) and its link to cardiovascular diseases (CVD). Here's a breakdown of the findings:

### 1. **Study Focus:**
   - **Lauric Acid (LA) and Dyslipidemia:** LA, a saturated fatty acid, aggravates dyslipidemia, a key factor in CVD.
   - **Red Blood Cells (RBCs) in CVD:** RBCs play a role in CVD, and eryptosis (a process where RBCs undergo programmed cell death) has been identified as a novel mechanism in CVD.

### 2. **Methodology:**
   - **Isolation of RBCs:** RBCs were isolated from heparin-anticoagulated whole blood.
   - **Exposure to LA:** Isolated RBCs were exposed to varying concentrations of LA for 24 hours at 37°C.

### 3. **Findings:**
   - **Hemolysis:** LA caused dose-responsive hemolysis (destruction of RBCs).
   - **Eryptosis Indicators:**
     - **Phosphatidylserine (PS) Exposure:** LA induced Ca2+-dependent PS exposure, indicating eryptosis.
     - **Cellular Changes:** LA led to cell shrinkage, increased granularity, and elevated erythrocyte sedimentation rate (ESR).
     - **Oxidative Stress:** LA exposure resulted in oxidative stress and accumulation of lipid peroxides in RBCs.
     - **CK1α Stimulation:** LA stimulated casein kinase 1α (CK1α), an enzyme associated with cell regulation.
   - **Whole Blood Effects:**
     - **Leukocyte Distribution:** LA disrupted leukocyte distribution, leading to an elevated neutrophil-lymphocyte ratio (NLR) due to selective toxicity to lymphocytes.

### 4. **Conclusion:**
   - **Pro-Eryptotic Potential:** LA demonstrated pro-eryptotic potential, contributing to programmed cell death in RBCs.
   - **Implications for CVD:** Understanding the mechanisms through which LA affects RBCs provides valuable insights for dietary interventions in preventing and managing CVD.

In summary, this study sheds light on how LA influences RBC physiology and contributes to eryptosis, providing crucial information for designing dietary interventions to mitigate the risk of CVD.