LipoCardium: endothelium-directed cyclopentenone prostaglandin-based liposome formulation that completely reverses atherosclerotic lesions
Autor: | Mauricio Krause, Rui Curi, Patricia Martins Bock, Sueli M. Senna, Dulcinéia Saes Parra Abdalla, Lisiane Paula Baldissera, Angela Maria Vicente Tavares, Lucila Ludmila Paula Gutierrez, Thiago Gomes Heck, Thais Martins de Lima, Joelso dos Santos Peralta, Gustavo Scola, Denise Jacques Lagranha, Paulo Ivo Homem de Bittencourt, Lavínia Almeida Cruz, Claudia J. Lagranha, Alexandre Maslinkiewicz, Daiane da Rocha Janner |
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Rok vydání: | 2006 |
Předmět: |
Male
Endothelium Inflammation Cyclopentanes Pharmacology chemistry.chemical_compound Mice medicine Macrophage Animals Rats Wistar Cyclopentenone prostaglandins Foam cell Neointimal hyperplasia Prostaglandins A Vascular disease business.industry Macrophages medicine.disease Atherosclerosis Lipid Metabolism Rats Endothelial stem cell Disease Models Animal medicine.anatomical_structure chemistry Immunology Liposomes Prostaglandins Feasibility Studies medicine.symptom Cardiology and Cardiovascular Medicine business |
Zdroj: | Atherosclerosis. 193(2) |
ISSN: | 0021-9150 |
Popis: | Atherosclerosis is a multifactorial inflammatory disease of blood vessels which decimates one in every three people in industrialized world. Despite the important newest clinical approaches, currently available strategies (e.g. nutritional, pharmacological and surgical) may only restrain the worsening of vascular disease. Since antiproliferative cyclopentenone prostaglandins (CP-PGs) are powerful anti-inflammatory agents, we developed a negatively charged liposome-based pharmaceutical formulation (LipoCardium) that specifically direct CP-PGs towards the injured arterial wall cells of atherosclerotic mice. In the blood stream, LipoCardium delivers its CP-PG contents only into activated arterial wall lining cells due to the presence of antibodies raised against vascular cell adhesion molecule-1 (VCAM-1), which is strongly expressed upon inflammation by endothelial cells and macrophage-foam cells as well. After 4 months in a high-lipid diet, all low-density lipoprotein receptor-deficient adult control mice died from myocardium infarction or stroke in less than 2 weeks, whereas LipoCardium-treated (2 weeks) animals (still under high-lipid diet) completely recovered from vascular injuries. In vitro studies using macrophage-foam cells suggested a tetravalent pattern for LipoCardium action: anti-inflammatory, antiproliferative (and pro-apoptotic only to foam cells), antilipogenic and cytoprotector (via heat-shock protein induction). These astonishing cellular effects were accompanied by a marked reduction in arterial wall thickness, neointimal hyperplasia and lipid accumulation, while guaranteed lifespan to be extended to the elderly age. Our findings suggest that LipoCardium may be safely tested in humans in a near future and may have conceptual implications in atherosclerosis therapy. |
Databáze: | OpenAIRE |
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