Anti-inflammatory effects of simvastatin during the resolution phase of experimentally formed venous thrombi. 2017

Yaping Feng, and Bo Lei, and Fuxian Zhang, and Luyuan Niu, and Huan Zhang, and Mingyi Zhang
Department of Vascular Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Deep venous thrombosis (DVT) is a common vascular disease and is closely linked to inflammation. Over the past decade, the potential antithrombotic effect of statins has been elucidated by clinical studies, primarily through focusing on DVT prevention. The effects of statins on DVT resolution and its underlying mechanisms have been rarely addressed. We established a rabbit model of the inferior vena cava (IVC) venous thrombosis. After 48 hours, the rabbits were treated with saline, heparin, simvastatin, or simvastatin combined with heparin, respectively, for 14 days. The migration of inflammatory cells (neutrophils, monocytes, lymphocytes) in the thrombi and injured venous wall, the plasma levels of interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1) and P-selectin, and local expression of MCP-1 and P-selectin in the venous wall were evaluated by histology, immunohistochemistry, and ELISA examinations. Our data showed that compared with saline and heparin controls, monotherapy of simvastatin and the adjunctive therapy with simvastatin and heparin significantly improved the thrombus resolution and reduced inflammatory cells migration into the venous wall, the release of the inflammatory cell adhesion molecule (P-selectin), inflammatory chemokine (MCP-1) and pleiotropic proinflammatory cytokines (IL-6) into the blood, and the local expression of P-selectin and MCP-1 in the venous wall. Simvastatin targets anti-inflammatory pathways during the resolution phase of a thrombus, providing a therapeutic potential in DVT resolution and post-thrombotic syndrome prevention.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008055 Lipids A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed) Lipid
D008297 Male Males
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000893 Anti-Inflammatory Agents Substances that reduce or suppress INFLAMMATION. Anti-Inflammatory Agent,Antiinflammatory Agent,Agents, Anti-Inflammatory,Agents, Antiinflammatory,Anti-Inflammatories,Antiinflammatories,Antiinflammatory Agents,Agent, Anti-Inflammatory,Agent, Antiinflammatory,Agents, Anti Inflammatory,Anti Inflammatories,Anti Inflammatory Agent,Anti Inflammatory Agents
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D019821 Simvastatin A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL. MK-733,Synvinolin,Zocor,MK 733,MK733
D020246 Venous Thrombosis The formation or presence of a blood clot (THROMBUS) within a vein. Deep Vein Thrombosis,Phlebothrombosis,Thrombosis, Deep Vein,Thrombosis, Venous,Deep Venous Thrombosis,Deep-Vein Thrombosis,Deep-Venous Thrombosis,Deep Vein Thromboses,Deep Venous Thromboses,Deep-Vein Thromboses,Deep-Venous Thromboses,Phlebothromboses,Thromboses, Deep Vein,Thromboses, Deep Venous,Thromboses, Deep-Vein,Thromboses, Deep-Venous,Thromboses, Venous,Thrombosis, Deep Venous,Thrombosis, Deep-Vein,Thrombosis, Deep-Venous,Vein Thromboses, Deep,Vein Thrombosis, Deep,Venous Thromboses,Venous Thromboses, Deep,Venous Thrombosis, Deep

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