Inhibition of endo-lysosomal function exacerbates vascular calcification.
Inhibition of endo-lysosomal function exacerbates vascular calcification.
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DOI：
10.1038/s41598-017-17540-6
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发表时间：
2018-02-21
影响因子：
4.6
通讯作者：
Guzman RJ
中科院分区：
文献类型：
--
作者：
Cai Y;Wang XL;Flores AM;Lin T;Guzman RJ
血管钙化是矿物质失衡的病理反应，在动脉粥样硬化、糖尿病和慢性肾病中普遍存在。当位于介质中时，它与心血管发病率和死亡率的增加高度相关，特别是在透析患者中。血管钙化受一系列内源性因素的调控。在本研究中，我们评估了溶酶体和内体抑制对血管平滑肌细胞（VSMCs）和主动脉环钙化的影响。我们观察到，在含有3.5 mM无机磷酸盐（Pi）和3 mM钙（Ca 2+）的钙化培养基中培养7天的VSMC中溶酶体功能增加。我们还发现，溶酶体标志物溶酶体相关膜蛋白2显着增加，并与成骨标志物共定位在钙化的骨小梁维生素D3治疗的大鼠。有趣的是，溶酶体抑制剂氯喹和内体抑制剂dynasore剂量依赖性地增强Pi + Ca 2+介导的VSMC钙化。溶酶体和内体功能的抑制也促进了VSMCs的成骨转化。此外，溶酶体抑制增加离体PI诱导的主动脉环中膜钙化。这些数据表明，内体-溶酶体系统可能在VSMC和中动脉钙化中起保护作用。
Vascular calcification is a pathologic response to mineral imbalances and is prevalent in atherosclerosis, diabetes mellitus, and chronic kidney disease. When located in the media, it is highly associated with increased cardiovascular morbidity and mortality, particularly in patients on dialysis. Vascular calcification is tightly regulated and controlled by a series of endogenous factors. In the present study, we assess the effects of lysosomal and endosomal inhibition on calcification in vascular smooth muscle cells (VSMCs) and aortic rings. We observed that lysosomal function was increased in VSMCs cultured in calcification medium containing 3.5 mM inorganic phosphate (Pi) and 3 mM calcium (Ca2+) for 7 days. We also found that the lysosomal marker lysosome-associated membrane protein 2 was markedly increased and colocalized with osteogenic markers in calcified aortas from vitamin D3-treated rats. Interestingly, both the lysosomal inhibitor chloroquine and the endosomal inhibitor dynasore dose-dependently enhanced Pi + Ca2+-mediated VSMC calcification. Inhibition of lysosomal and endosomal function also promoted osteogenic transformation of VSMCs. Additionally, lysosome inhibition increased Pi-induced medial calcification of aortic rings ex vivo. These data suggest that the endosome-lysosome system may play a protective role in VSMC and medial artery calcification.
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DOI：
10.1523/jneurosci.6412-10.2011
发表时间：
2011-05-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lee S;Sato Y;Nixon RA
通讯作者：
Nixon RA
影响因子：
9.3
作者：
Leopold JA
通讯作者：
Leopold JA
DOI：
10.1161/atvbaha.110.212621
发表时间：
2011-03
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Cai Y;Miller CL;Nagel DJ;Jeon KI;Lim S;Gao P;Knight PA;Yan C
通讯作者：
Yan C
影响因子：
6.1
作者：
Guérin, AP;London, GM;Metivier, F
通讯作者：
Metivier, F
影响因子：
5.1
作者：
Guzman, Raul J.;Bian, Aihua;Shintani, Ayumi;Stein, C. Michael
通讯作者：
Stein, C. Michael