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Patients with combined hypercholesterolemia-hypertriglyceridemia show an increased monocyte-endothelial cell adhesion
M de Gruijter1, N Hoogerbrugge, M A van Rijn
1MGC-Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Insights
Combined hypercholesterolemia-hypertriglycerinemia (CHH) increases monocyte adhesion to blood vessel walls. This heightened adhesion, driven by elevated triglycerides, contributes to atherosclerosis development.
Area of Science:
- Cardiovascular Science
- Immunology
- Metabolic Disorders
Background:
- Hypercholesterolemia (HC) is a key risk factor for atherosclerosis.
- Familial hypercholesterolemia (FH) and combined hypercholesterolemia-hypertriglycerinemia (CHH) increase the risk of premature atherosclerosis.
- In vivo studies show diet-induced HC elevates monocyte adhesion to the endothelium, potentially initiating atherosclerotic plaque formation.
Purpose of the Study:
- To investigate the in vitro binding of monocytes in patients with hypercholesterolemia.
- To determine the specific alterations in monocytes contributing to increased adhesion.
- To identify the primary determinant of altered monocyte adhesion in CHH.
Main Methods:
- Isolated monocytes from CHH and FH patients were incubated with cultured human umbilical vein endothelial cells (HUVEC).
- Monocyte adhesion to HUVEC was quantified and compared between patient groups and healthy subjects.
- The role of hypertriglyceridemia versus hypercholesterolemia alone was assessed.
Main Results:
- Monocytes from CHH patients showed a significant 60% increase in adhesion to HUVEC compared to healthy subjects.
- No significant increase in monocyte adhesion was observed with monocytes from untreated FH patients.
- These findings indicate in vivo alterations in CHH monocytes enhance their adhesion to HUVEC.
Conclusions:
- Combined hypercholesterolemia-hypertriglycerinemia induces monocyte alterations leading to increased in vitro adhesion.
- Elevated plasma triglycerides appear to be the major determinant of this altered monocyte adhesion.
- Hypercholesterolemia alone does not appear to induce this specific monocyte adhesion defect.
Abstract:
Hypercholesterolemia (HC) is one of the primary risk factors for atherosclerosis. Patients with familial hypercholesterolemia (FH) or combined hypercholesterolemia-hypertriglycerinemia (CHH) are at risk to develop premature atherosclerosis. Animal models have revealed that diet-induced HC in vivo leads to an increased adhesion of monocytes to the endothelium of the vessel wall. Changes in the monocytes, endothelial cells, or serum components may lead to the increased monocyte adhesion that results in atherosclerotic plaque formation. In the present study, we investigated the binding of the monocyte in an in vitro system. Incubation of freshly isolated monocytes from CHH patients with cultured human umbilical vein endothelial cells (HUVEC) gave a significant 60% increase in monocyte adhesion when compared with monocytes from healthy subjects. No such increase was observed using monocytes from nontreated FH patients. These data suggest that CHH results in in vivo alterations of the monocytes that lead to an increased in vitro adhesion to HUVEC, and that an increased level of plasma triglycerides is the major determinant, since HC alone does not induce this alteration.