Abstract
The causes of increased rates of myocardial infarctions and strokes by application of non-steroidal antiinflammatory agents (NSAIDs) are unclear. Here we present a biochemical model that the long-term vascular effects of NSAIDs can be consequences of their antiproliferative cellular mechanism. The analysis of the model suggests that the intramitochondrial uncoupling of oxidative phosphorylation induced by NSAIDs increases, through a reduced activity of ATP-dependent ionic pumps, the intra-cellular calcium x phosphate product with a consecutively increased formation and export of various calcium phosphate compounds. The latter cause, by chemical replication mechanisms of arterial hydroxyapatite deposits, a metatstatic calcifying vascular process. This sclerogenic vascular mineralization corresponds to an early arteriosclerotic development resembling the Monckebergs media calcification. The mechanism shows direct analogies to the accelerated and metastatic calcification of coronary arteries seen in chronic kidney disease and dialysis. This appears an extra-cellular time-lapse version of the protracted cell model. The induction of this degenerative mechanism may explain the increased number of adverse cardiovascular, renovascular and cerebrovascular effects of NSAIDs as they are observed in long-term therapies.
Keywords: NSAID, metastatic calcification, arteriosclerosis, hypertension, chronic kidney disease, biochemical model
Medicinal Chemistry
Title: A Model on the Induction of Adverse Vascular Long-Term Effects of NSAIDs
Volume: 5 Issue: 1
Author(s): Rainer K. Liedtke
Affiliation:
Keywords: NSAID, metastatic calcification, arteriosclerosis, hypertension, chronic kidney disease, biochemical model
Abstract: The causes of increased rates of myocardial infarctions and strokes by application of non-steroidal antiinflammatory agents (NSAIDs) are unclear. Here we present a biochemical model that the long-term vascular effects of NSAIDs can be consequences of their antiproliferative cellular mechanism. The analysis of the model suggests that the intramitochondrial uncoupling of oxidative phosphorylation induced by NSAIDs increases, through a reduced activity of ATP-dependent ionic pumps, the intra-cellular calcium x phosphate product with a consecutively increased formation and export of various calcium phosphate compounds. The latter cause, by chemical replication mechanisms of arterial hydroxyapatite deposits, a metatstatic calcifying vascular process. This sclerogenic vascular mineralization corresponds to an early arteriosclerotic development resembling the Monckebergs media calcification. The mechanism shows direct analogies to the accelerated and metastatic calcification of coronary arteries seen in chronic kidney disease and dialysis. This appears an extra-cellular time-lapse version of the protracted cell model. The induction of this degenerative mechanism may explain the increased number of adverse cardiovascular, renovascular and cerebrovascular effects of NSAIDs as they are observed in long-term therapies.
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Liedtke K. Rainer, A Model on the Induction of Adverse Vascular Long-Term Effects of NSAIDs, Medicinal Chemistry 2009; 5 (1) . https://dx.doi.org/10.2174/157340609787049235
DOI https://dx.doi.org/10.2174/157340609787049235 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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