Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Department of Nephrology and Hypertension, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.
Hypertens Res. 2018 Sep;41(9):699-707. doi: 10.1038/s41440-018-0067-8. Epub 2018 Jun 27.
The ATP2B1 gene is associated with hypertension. We previously reported that systemic heterozygous ATP2B1-null (ATP2B1) mice exhibited hypertension due to impaired endothelial nitric oxide synthase (eNOS) activity and decreased nitric oxide (NO) production. The ATP2B1 gene encodes plasma membrane calcium ATPase 1 (PMCA1), which has been thought to regulate only intracellular Ca concentration. However, recently, it has been suggested that ATP2B1 works not only at cellular levels, but also throughout the entire body, including in the calcium metabolism, using small intestine-specific ATP2B1 knockout mice. To clarify the roles of ATP2B1 in the entire body and the effects of ATP2B1 on blood pressure, we examined the alterations of calcium related factors in ATP2B1 mice. ATP2B1 mice exhibited hypocalcemia. The expression of ATP2B1 in the kidney and small intestine decreased, and hypercalciuria was confirmed in ATP2B1 mice. The intact-PTH levels were lower, and bone mineral density was increased in these mice. These results suggest that hypocalcemia is mainly a result of inhibited bone resorption without compensation by PTH secretion in the case of ATP2B1 knockout. Moreover, NO production may be affected by reduced PTH secretion, which may cause the increase in vascular contractility in these mice. The ATP2B1 gene is important for not only intra-cellular calcium regulation but also for calcium homeostasis and blood pressure control.
ATP2B1 基因与高血压有关。我们之前报道过，全身杂合子 ATP2B1 敲除（ATP2B1）小鼠由于内皮型一氧化氮合酶（eNOS）活性受损和一氧化氮（NO）产生减少而表现出高血压。ATP2B1 基因编码质膜钙 ATP 酶 1（PMCA1），它被认为仅调节细胞内 Ca 浓度。然而，最近有人提出，ATP2B1 的作用不仅在细胞水平上，而且在整个身体中，包括在钙代谢中，使用小肠特异性 ATP2B1 敲除小鼠。为了阐明 ATP2B1 在整个身体中的作用以及 ATP2B1 对血压的影响，我们检查了 ATP2B1 小鼠中与钙相关的因素的变化。ATP2B1 小鼠表现出低钙血症。肾脏和小肠中的 ATP2B1 表达减少，并且在 ATP2B1 小鼠中确认了高钙尿症。这些小鼠的完整甲状旁腺激素水平较低，骨矿物质密度增加。这些结果表明，低钙血症主要是由于骨吸收受到抑制而没有甲状旁腺激素分泌代偿的结果。此外，NO 产生可能受到甲状旁腺激素分泌减少的影响，这可能导致这些小鼠血管收缩性增加。ATP2B1 基因不仅对细胞内钙调节很重要，而且对钙平衡和血压控制也很重要。
