Pleiotropic effects of statins via interaction with the lipid bilayer: A combined approach
| Autor: | Shamish Ganpule, Gintaras Valincius, Aiste Zentelyte, Giulio Preta, Tadas Penkauskas |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Hypercholesterolemia Lipid Bilayers Biophysics Pharmacology Biochemistry Cell membrane 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Humans Lipid bilayer Lipid raft Cholesterol Anticholesteremic Agents Cell Membrane nutritional and metabolic diseases Cell Biology 030104 developmental biology Membrane medicine.anatomical_structure chemistry Cardiovascular Diseases Cancer cell Drug delivery Lipophilicity lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Hydrophobic and Hydrophilic Interactions 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et biophysica acta. Biomembranes. 1862(9) |
| ISSN: | 1879-2642 |
| Popis: | Statins are effective inhibitors of cholesterol biosynthesis, largely used for prevention of cardiovascular diseases induced by hypercholesterolemia. However, their use in different clinical trials clearly indicate that the general benefits observed with statins are also related to effects beyond the cholesterol lowering. Increasing evidences suggest that some of these cholesterol-independent or "pleiotropic" effects of statins involve the interaction and modification of the membrane bilayers. In this manuscript, using a combined approach based on biophysical (electrochemical impedance spectroscopy on tethered bilayer lipid membranes) and biological methods (hemolysis on erythrocytes and immunocytochemistry on cancer cells), we demonstrate that lipophilic, but not hydrophilic statins are capable of reducing the damage caused by cholesterol-dependent cytolysins. This protection correlates with statins lipophilicity and capacity to interact with the lipid bilayer. Our data suggests lipophilic statins associate with membranes and interfere with the ability of cholesterol dependent cytolysins, to bind to membrane cholesterol. Evaluation of the capacity of statins to modulate cell membrane properties is essential for developing a correct therapeutic approach for cardiovascular diseases as well as for understanding the potential of this class of drugs as adjuvants for drug delivery. |
| Databáze: | OpenAIRE |
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