血管内皮细胞凋亡是糖尿病大血管病变发病的重要病理基础，课题组的前期研究发现，高糖通过上调钠钙交换蛋白SLC24A6的表达，升高细胞内Ca2+浓度，增强Calcineurin磷酸酶的活性，降低BAD的磷酸化水平，最终导致人主动脉内皮细胞（HAEC）凋亡，为此，课题组提出了SLC24A6在糖尿病大血管病变发病过程中可能的分子机制：高糖诱导的"SLC24A6-Ca2+-Calcineurin/BAD"信号通路的激活引起血管内皮细胞的凋亡，从而导致大血管病变的发生，目前课题组已成功建立了SLC24A6条件性基因剔除小鼠模型。课题组期望得到国家自然科学基金的资助，将SLC24A6的研究深入下去，在细胞水平、糖尿病动物模型以及血管内皮细胞SLC24A6特异剔除动物模型的层面上深入研究"SLC24A6-Ca2+-Calcineurin/BAD"信号通路在糖尿病大血管病变中的作用，并明确其中的分子机制。

Apoptosis of vascular endothelial cells plays an important role in the phathogenesis of diabetic macrovascular complications. Our previous studies indicated that high glucose culture elevated intracellular Ca2+ concentration, increased calcinuerin phosphatase activity, and then decreased phosphorylation of BAD, and finally resulted in apoptosis of human aortic endothelial cell (HAEC). So we proposed the possible molecular mechanism of SLC24A6 underlying the pathogenesis of diabetic macrovascular complications as follows: Apoptosis of vascular endothelial cells which was caused by high glucose-induced activation of SLC24A6-Ca2+-Calcineurin/BAD signaling pathway contributed to diabetic macrovascular complications. SLC24A6 conditional knockout mouse models have been successfully established in our study. We are looking forward to getting the grant from NSFC which will support us to push the study of SLC24A6 extensively. In the future study, we are going to focus on animal models including diabetic animal models and vascular endothelial-specific SLC24A6 knockout animal models and cell culture experiments, try to elucidate the role and the molecular mechanism of SLC24A6-Ca2+-Calcineurin/BAD signaling pathway in the phathogenesis of diabetic macrovascular complications.