Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphosphonates are used for the treatment of bone resorption, hypercalcemia, osteoporosis and Paget's disease. Etidronate, pamidronate and clodronate also inhibit the development of experimental atherosclerosis without altering serum lipid profile. Bisphosphonates inhibit the arterial calcification, lipid accumulation and fibrosis. They accumulate extensively in arterial walls and suppress macrophages in atheromatous lesions. In macrophage cultures, bisphosphonates inhibit the cellular accumulation and degradation of atherogenic LDL-cholesterol and foam cell formation. Further, they inhibit various enzymes involved in cell signal transduction and cholesterol biosynthesis. Recently, etidronate has been shown to inhibit the thickening of carotid arterial wall even in man.
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PMID:Bisphosphonates and atherosclerosis. 1192 58

Etidronate and clodronate are bisphosphonates that inhibit the development of experimental atherosclerosis. Etidronate decreases the intimamedia thickness of carotid artery even in man. Liposome-encapsulated bisphosphonates inhibit the cellular metabolism of atherogenic, modified low-density lipoprotein (acetyl-LDL) by cultured macrophages. In the present study, the effects of new bisphosphonate tiludronate and nitrogen-containing bisphosphonate alendronate on cell viability and cellular uptake and degradation of acetyl-LDL were investigated in vitro with macrophages and arterial smooth muscle cells, which have a significant role in atherogenesis. Tiludronate and alendronate decreased the viability of RAW 264 macrophages at high concentration (1,000 microM; p < 0.05), while liposome-encapsulated drugs suppressed the viability at concentrations of 30-300 microM. At concentrations greater than or equal to 10 microM, tiludronate and alendronate inhibited the uptake and degradation of acetyl-LDL by RAW 264 cells in a concentration-dependent manner (p < 0.001). None of the bisphosphonates affected the viability of smooth muscle cells, and none but alendronate at a high concentration (1,000 microM) inhibited the uptake and degradation of acetyl-LDL by smooth muscle cells. The results show that tiludronate and alendronate inhibit the atherogenic activity of macrophages in vitro, as shown previously with etidronate and clodronate, providing further evidence for the antiatherogenic effects of bisphosphonates.
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PMID:Suppression of viability and acetyl-LDL metabolism in RAW 264 macrophage-like and smooth muscle cells by bisphosphonates in vitro. 1250 Apr 27

Etidronate, an analogue of first generation of bisphosphonates, has inhibitory actions on mineralization and hydroxyapatite crystal formation, which is therefore used as a drug to treat ectopic ossification in cases with total hip arthroplasty and spinal cord injury. The effect of bisphosphonates to prevent calcification could be associated with the physical property to attach tightly to hydroxyapatite crystals in bone matrix. A recent investigation suggested that bisphosphonates might prevent arterial calcification through a mechanism associated with the enhanced production of parathyroid hormone-related peptide from vascular smooth muscle cells. A derivative of bisphosphonates to inhibit vascular calcification in atherosclerosis is expected and should be developed in the near future.
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PMID:[Regulation of calcification by bisphosphonates]. 1557 56

The increasing knowledge on bone calcification processes has revealed some similarities with vascular tissue, where calcifications of arteries and cardiac valves contribute to several cardiovascular problems, such as heart failure, systolic hypertension, and myocardial and peripheral ischemic disease. Bisphosphonates have been used extensively for over two decades for the treatment of diseases associated with excessive bone resorption, i.e., osteoporosis, osteolytic bone metastasis, hypercalcemia and Paget's disease, by blocking osteoclastic function. Etidronate, pamidronate and clodronate has been shown to inhibit the development of experimental atherosclerosis, and proposed mechanisms for this action include inhibition of arterial calcification and lipid accumulation, degradation of atherogenic LDL-cholesterol and reduced foam cell formation. Bisphosphonates inhibit various enzymes involved in cholesterol biosynthesis and suppress macrophages in atheromatous lesions. The possibility of pharmacological agents that effectively treat both osteoporosis and atherosclerosis is attractive, however, current evidence is not conclusive and further research is necessary to confirm these actions in the clinical setting.
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PMID:Bisphosphonates and atherosclerosis: why? 1721 1