CALCIFICATION IN THE CARDIOVASCULAR SYSTEM

心脏病是死亡、残疾和经济损失的主要原因。 通常，心脏病与钙化引起的血管阻塞相吻合。 斑块 总的目标是编制关于 心血管沉积物（CD）的动力学和结构特性， 可防止CD形成的药物的抑制机制。 我们 建议：I. 评估各种新型药物的治疗潜力 用于控制钙化沉积物形成和生长的膦酸盐药物 通过自发沉淀和接种生长的体外实验， 磷酸钙 I. 研究药物对 溶解和水解的OCP，以调查的潜力， 稳定心血管钙化前体和抑制 前体向羟基磷灰石的转化， CD的组成部分。 三. 遵循前体在体内的形成， 矿化的早期阶段，并研究新的抑制作用 通过检测（32 P- 热解技术）的酸性磷酸根离子（HPO 4）在钙化矿床 在大鼠皮下植入的牛心包上形成。 四. 测量OCP-碳酸盐的溶解和水解， 生理条件。 OCP-CO 3的形成及其向 已提出类似于CD的碳酸磷灰石作为替代物 碳酸盐通过OCP-CO 3中间体掺入CD的机理。 五、在体外研究回收的CD上晶体生长的机制 通过接种磷酸钙的过饱和溶液， 天然和脱蛋白CD粉末。 六. 研究钙的抑制作用 体外CD上的磷酸盐生长，以确定已知的 双膦酸盐对成熟CD上晶体生长的影响。 七. 机理研究 通过以下方式吸收氟化物， CD并与拟议前体的吸收进行比较。 最终目标是 了解心血管钙化的过程， 动脉粥样硬化的治疗和预防 破坏植入的生物假体。

Heart diseases are a major cause of death, disability and economic los. Often, heart conditions coincide with blood vessel blockage by calcified plaques. The overall objective is to develop sufficient information on the kinetic and structural properties of cardiovascular deposits (CD) and on the inhibition mechanisms of agents that can prevent formation of CD. We propose to: I. Assess the therapeutic potential of various novel phosphonate drugs for control of formation and growth of calcified deposits by in vitro experiments of spontaneous precipitation and seeded growth of calcium phosphate. I. Study the inhibitory effects of drugs on dissolution and hydrolysis of OCP in order to investigate the potential of the drugs to stabilize cardiovascular calcification precursors and inhibit the transformation of the precursors to hydroxyapatite, the main constituent of CD. III. Follow the formation of precursors in vivo in the early stages of mineralization and study the inhibition effect of novel phosphonates on their formation and transformation by detection (32P- pyrolysis technique) of acidic phosphate ions (HPO4) in calcified deposits formed on subcutaneously implanted Bovine pericardium in rats. IV. Measure the dissolution and hydrolysis of OCP-carbonates under physiological conditions. Formation of OCP-CO3 and its transformation to carbonate apatite similar to CD has been proposed as an alternative mechanism for incorporation of carbonate into CD via OCP-CO3 intermediate. V. Investigate in vitro the mechanism of crystal growth on CD retrieved from patients by seeding supersaturated solutions of calcium phosphate with native and deproteinated CD powders. VI. Study the inhibition of calcium phosphate growth on CD in vitro in order to determine the effect of known bisphosphonates on crystal growth on mature CD. VII. Study the mechanism of incorporation of fluoride into CD by following the uptake of fluoride by CD and comparing with uptake by proposed precursors. The ultimate goal is to understand the process of cardiovascular calcification and to develop therapeutic treatments for atherosclerosis and prevention of the destruction of implanted bioprostheses.