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Increased thrombogenic potential of human monocyte-derived macrophages spontaneously transformed into foam cells
1Institute of Pharmacological Sciences, E. Grossi Paoletti Center, University of Milan, Italy.
Abstract:
This study investigated whether spontaneous lipid enrichment of human macrophages affects their thrombogenic potential as measured by increased production of tissue factor (TF) and plasminogen activation inhibitor types 1 and 2 (PAI-1 and PAI-2). Macrophages were obtained following a 7-day culture period of monocytes, isolated from the same donor, in autologous serum (HS) or in fetal bovine serum (FBS). Those cultured in HS underwent marked lipid accumulation relative to those cultured in FBS that was accompanied by increased production of TF and PAI-1, but not of PAI-2, and decreased production of interleukin-1beta. They also contained more arachidonic and linoleic acid and lower amounts of n-3 polyunsaturated fatty acids, particularly docosahexaenoic acid (22: 6). These data indicate that the transformation of macrophages into foam cells results in an increase in their thrombogenic and antifibrinolytic potential and provide a possible explanation of the thrombotic sequelae frequently consequent on plaque fissuring and disruption.
Insights
Lipid-enriched macrophages, or foam cells, show increased thrombogenic potential, producing more tissue factor (TF) and plasminogen activation inhibitor-1 (PAI-1). This suggests a link between foam cell formation and thrombotic events in conditions like plaque disruption.
Area of Science:
- Immunology
- Cardiovascular Biology
- Lipid Metabolism
Background:
- Macrophages play a critical role in the inflammatory response within atherosclerotic plaques.
- Lipid accumulation in macrophages is a hallmark of foam cell formation, a key event in atherogenesis.
- The thrombogenic potential of macrophages, particularly their role in initiating coagulation, is not fully understood.
Purpose of the Study:
- To investigate the impact of spontaneous lipid enrichment on human macrophage thrombogenic potential.
- To assess the production of key pro-thrombotic and antifibrinolytic factors by lipid-laden macrophages.
- To explore the relationship between macrophage lipid composition and their thrombotic activity.
Main Methods:
- Human monocytes were isolated and cultured for 7 days in autologous serum (HS) or fetal bovine serum (FBS) to induce lipid accumulation.
- Macrophage lipid content, including specific fatty acids, was analyzed.
- Production of tissue factor (TF), plasminogen activation inhibitor-1 (PAI-1), plasminogen activation inhibitor-2 (PAI-2), and interleukin-1beta was quantified.
Main Results:
- Macrophages cultured in HS exhibited significant lipid accumulation compared to those in FBS.
- HS-cultured macrophages showed increased production of TF and PAI-1, but not PAI-2.
- Lipid-enriched macrophages contained higher levels of arachidonic and linoleic acids and lower levels of n-3 polyunsaturated fatty acids, including docosahexaenoic acid (22:6).
- Interleukin-1beta production was decreased in lipid-rich macrophages.
Conclusions:
- Spontaneous lipid enrichment transforms macrophages into foam cells with enhanced thrombogenic and antifibrinolytic potential.
- Increased TF and PAI-1 production by foam cells may contribute to thrombotic events following plaque rupture.
- Macrophage fatty acid composition is altered during lipid loading and may influence their pro-thrombotic state.