Friday, November 27, 2009

The potential anti-atherosclerotic effects of proton pump inhibitors

A recent study has shown that calcium phosphate crystals of approximately 1 micron or less in diameter caused rapid rises in intracellular calcium concentration, an effect that was inhibited by the lysosomal proton pump inhibitor, bafilomycin A1 which also blocked vascular smooth muscle cell death. This suggested to the authors that calcium phosphate crystals are rapidly degraded in lysosomes and subsequent acidification leads to the release of calcium into the cell (1)
A study looking to demonstrate that when subintimal macrophages come into contact with LDL aggregates, an extracellular, acidic, hydrolytic compartment (a lysosomal synapse) is formed., with bafilomycin A1 blocking the free cholesterol production in this compartment (2)
Another study has discussed about the potential anti-atherosclerotic effects of proton pump inhibitors (3).
The above studies give great support to the acidity theory of atherosclerosis concept (4)
1) Calcium Phosphate Crystals Induce Cell Death in Human Vascular Smooth Muscle Cells: A Potential Mechanism in Atherosclerotic Plaque Destabilization, Alexandra E. Ewence et al, Circ. Res. 2008;103;e28-e34; at
2) Macrophages Create an Acidic Extracellular Hydrolytic Compartment to Digest Aggregated Lipoproteins, Haka, A.S., I. Grosheva, E. Chiang, A.R. Buxbaum, B.A. Baird, L.M. Pierini and F.R. Maxfield. Mol. Biol. Cell, in press 2009, at
3) The potential anti-xanthoma and anti-atherosclerotic effects of proton pump inhibitors, M. R. Namazi, MD and M. Sharifian, MD. Journal of Clinical Pharmacy and Therapeutics (2008) 33, 579–580
4) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at

No comments:

Post a Comment