TY - JOUR
T1 - Pharmacological control of phagocyte function
T2 - Inhibition of cholesterol accumulation
AU - Paoletti, R.
AU - Bellosta, S.
AU - Bernini, F.
PY - 1997/12/15
Y1 - 1997/12/15
N2 - Phagocytes play a major role in several diseases. In particular mononuclear phagocyte-derived foam cells have a prominent role in the development of the atherosclerotic lesions. Macrophages are present in all stages of atherogenesis: they internalize lipoproteins and accumulate cholesterol. Moreover, lipid-filled macrophages, by secreting extracellular matrix-degrading enzymes, may weaken rupture-prone atherosclerotic plaques, thus increasing the probability of precipitating atherosclerotic acute symptoms (i.e., myocardial infarction, angina, etc.). Therefore, control of cellular functions and cholesterol accumulation in macrophages represent pharmacological targets against atherosclerosis. In our laboratory we studied the effect of calcium antagonists on cellular cholesterol esterification in cultured macrophages. We also demonstrated that the HMG-CoA reductase inhibitors (vastatins) fluvastatin and simvastatin prevented cholesterol deposition in cultured human and murine macrophage by inhibiting modified LDL endocytosis. Interestingly, vastatin activity was more pronounced in cholesterol-loaded macrophages (i.e., foam cells) than in normal cells. In conclusion, in vitro pharmacological control of cholesterol accumulation in macrophages may be achieved with some calcium antagonists and vastatins independently of their effects on blood pressure or cholesterolemia.
AB - Phagocytes play a major role in several diseases. In particular mononuclear phagocyte-derived foam cells have a prominent role in the development of the atherosclerotic lesions. Macrophages are present in all stages of atherogenesis: they internalize lipoproteins and accumulate cholesterol. Moreover, lipid-filled macrophages, by secreting extracellular matrix-degrading enzymes, may weaken rupture-prone atherosclerotic plaques, thus increasing the probability of precipitating atherosclerotic acute symptoms (i.e., myocardial infarction, angina, etc.). Therefore, control of cellular functions and cholesterol accumulation in macrophages represent pharmacological targets against atherosclerosis. In our laboratory we studied the effect of calcium antagonists on cellular cholesterol esterification in cultured macrophages. We also demonstrated that the HMG-CoA reductase inhibitors (vastatins) fluvastatin and simvastatin prevented cholesterol deposition in cultured human and murine macrophage by inhibiting modified LDL endocytosis. Interestingly, vastatin activity was more pronounced in cholesterol-loaded macrophages (i.e., foam cells) than in normal cells. In conclusion, in vitro pharmacological control of cholesterol accumulation in macrophages may be achieved with some calcium antagonists and vastatins independently of their effects on blood pressure or cholesterolemia.
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U2 - 10.1111/j.1749-6632.1997.tb46260.x
DO - 10.1111/j.1749-6632.1997.tb46260.x
M3 - Article
C2 - 9704060
AN - SCOPUS:0031574094
VL - 832
SP - 322
EP - 329
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
SN - 0077-8923
ER -