Department of Medicine, School of Medicine, University of California , Los Angeles, California.
Department of Physiology, School of Medicine, University of California , Los Angeles, California.
Am J Physiol Heart Circ Physiol. 2018 Jun 1;314(6):H1203-H1213. doi: 10.1152/ajpheart.00718.2017. Epub 2018 Feb 16.
Calcific aortic vasculopathy correlates with bone loss in osteoporosis in an age-independent manner. Prior work suggests that teriparatide, the bone anabolic treatment for postmenopausal osteoporosis, may inhibit the onset of aortic calcification. Whether teriparatide affects the progression of preexisting aortic calcification, widespread among this patient population, is unknown. Female apolipoprotein E-deficient mice were aged for over 1 yr to induce aortic calcification, treated for 4.5 wk with daily injections of control vehicle (PBS), 40 µg/kg teriparatide (PTH40), or 400 µg/kg teriparatide (PTH400), and assayed for aortic calcification by microcomputed tomography (microCT) before and after treatment. In a followup cohort, aged female apolipoprotein E-deficient mice were treated with PBS or PTH400 and assayed for aortic calcification by serial microCT and micropositron emission tomography. In both cohorts, aortic calcification detected by microCT progressed similarly in all groups. Mean aortic F-NaF incorporation, detected by serial micropositron emission tomography, increased in the PBS-treated group (+14 ± 5%). In contrast, F-NaF incorporation decreased in the PTH400-treated group (-33 ± 20%, P = 0.03). Quantitative histochemical analysis by Alizarin red staining revealed a lower mineral surface area index in the PTH400-treated group compared with the PBS-treated group ( P = 0.04). Furthermore, Masson trichrome staining showed a significant increase in collagen deposition in the left ventricular myocardium of mice that received PTH400 [2.1 ± 0.6% vs. control mice (0.5 ± 0.1%), P = 0.02]. In summary, although teriparatide may not affect the calcium mineral content of aortic calcification, it reduces F-NaF uptake in calcified lesions, suggesting the possibility that it may reduce mineral surface area with potential impact on plaque stability. NEW & NOTEWORTHY Parathyroid hormone regulates bone mineralization and may also affect vascular calcification, which is an important issue, given that its active fragment, teriparatide, is widely used for the treatment of osteoporosis. To determine whether teriparatide alters vascular calcification, we imaged aortic calcification in mice treated with teriparatide and control mice. Although teriparatide did not affect the calcium content of cardiovascular deposits, it reduced their fluoride tracer uptake.
钙磷代谢性主动脉血管病与骨质疏松症的骨丢失呈年龄非依赖性相关。先前的研究表明,特立帕肽是治疗绝经后骨质疏松症的骨合成代谢药物,可能抑制主动脉钙化的发生。然而,特立帕肽是否会影响该患者群体中广泛存在的主动脉钙化的进展尚不清楚。
我们将载脂蛋白 E 基因敲除的雌性小鼠饲养超过 1 年以诱导主动脉钙化,然后用每日注射对照载体(PBS)、40 µg/kg 特立帕肽(PTH40)或 400 µg/kg 特立帕肽(PTH400)治疗 4.5 周,并用 microCT(微计算机断层扫描)检测治疗前后的主动脉钙化。在后续的队列中,我们用 PBS 或 PTH400 治疗载脂蛋白 E 基因敲除的雌性小鼠,并通过连续 microCT 和 micro-PET 检测主动脉钙化。在两个队列中,microCT 检测到的主动脉钙化在所有组中均以相似的速度进展。通过连续 micro-PET 检测到的平均主动脉 F-NaF 掺入量在 PBS 处理组中增加(+14±5%)。相比之下,PTH400 处理组中的 F-NaF 掺入量减少(-33±20%,P=0.03)。茜素红染色的定量组织化学分析显示,与 PBS 处理组相比,PTH400 处理组的矿物质表面积指数较低(P=0.04)。此外,Masson 三色染色显示,接受 PTH400 治疗的小鼠左心室心肌中的胶原蛋白沉积显著增加[2.1±0.6%与对照组(0.5±0.1%),P=0.02]。
总之,尽管特立帕肽可能不会影响主动脉钙化的钙矿物质含量,但它降低了钙化病变中的 F-NaF 摄取,这表明它可能减少矿物质表面积,从而可能影响斑块稳定性。
甲状旁腺激素调节骨矿化,也可能影响血管钙化,鉴于其活性片段特立帕肽广泛用于骨质疏松症的治疗,这是一个重要问题。为了确定特立帕肽是否会改变血管钙化,我们对接受特立帕肽和对照治疗的小鼠的主动脉钙化进行了成像。尽管特立帕肽对心血管沉积物的钙含量没有影响,但它降低了氟化物示踪剂的摄取。