Role of bicarbonate/CO2 buffer in the initiation of vesicle-mediated calcification: mechanisms of aortic calcification related to atherosclerosis.
Calcifying vesicles play an important role in the mechanism of aortic calcification induced by dietary cholesterol interventions. This study was initiated to test the hypothesis that alterations in the ratio of bicarbonate/CO2, which is a main physiological buffer, could affect vesicle-mediated calcification. Using rabbits as a model, in vitro calcification of vesicles isolated from aortas was performed to study the effect of the bicarbonate buffer on the mineralization process. When Tris buffer was initially used to maintain pH of the media, ATP-dependent vesicle calcification increased with pH of calcifying media. By replacing Tris with physiological bicarbonate/CO2 buffer, ATP-dependent vesicle calcification increased rapidly with increased ratios of bicarbonate/CO2. The increase appears to be a result of elevated levels of pH through the alteration in the ratios of bicarbonate/CO2. The effect of the physiological concentration of bicarbonate (30 mM) on pH of calcifying media was remarkable since 50 mM of Tris buffer at pH 7.6 failed to prevent a rapid rise in pH under atmospheric CO2. The effect of bicarbonate and CO2 on vesicle calcification was dependent on the ratio of the surface area to the volume of calcifying media, since the ratio profoundly affects the exchange rate between the gas and liquid phases of CO2. Although the pathological conditions that alter the pH remain unknown, it is conceivable that blockage in the supply of blood CO2 to the media by intimal thickening in the lesions could contribute to focal calcification. We conclude that bicarbonate buffer could provide a dynamic and rapid transitional increase in pH of extracellular fluids, thereby creating a favorable condition for the initiation of vesicle-mediated calcification under pathological conditions.
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City 66160, USA. hhsu@kumc.edu
Howard H T
HH
Hsu
Benjamin G
BG
Abbo
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000494:pharmacology; D000821:Animal Feed; D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism*; D001639:Bicarbonates / Q000737:chemistry / Q000378:metabolism*; D002021:Buffers; D002113:Calcification, Physiologic; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002245:Carbon Dioxide / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D011817:Rabbits; D017693:Sodium Bicarbonate / Q000494:pharmacology; D013997:Time Factors
D001639:Bicarbonates; D002021:Buffers; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D017693:Sodium Bicarbonate; D002784:Cholesterol; D002118:Calcium