Subtherapeutic lithium supplementation causes physiological eccentric cardiac hypertrophy in young-adult wild-type male mice.

IF 2.2 Q3 PHYSIOLOGY
Sophie I Hamstra, Mia S Geromella, Peter Tiidus, Panagiota Klentrou, Rebecca E K MacPherson, Val A Fajardo
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引用次数: 0

Abstract

Six weeks of low-dose lithium (Li) supplementation has been shown to improve the activity of cardiac sarco(endo)plasmic reticulum calcium (Ca2+)-ATPase (SERCA) in C57BL/6J wild-type (WT) male mice. Improvements in myocardial SERCA function can lead to improvements in systolic and diastolic function in various rodent models. In this study, we tested the hypothesis that 12 weeks of subtherapeutic Li supplementation (10 mg/kg/day) would enhance SERCA function and positively influence cardiac contractility and morphology. Cardiac function and morphology were assessed using high-frequency ultrasound in the final week of Li treatment. Subsequently, SERCA activity, Ca2+ uptake assays, and Western blotting for glycogen synthase kinase-3β, SERCA2, and its inhibitor phospholamban (PLN) were performed on isolated left ventricle tissue. After 12 weeks of subtherapeutic Li supplementation, the heart underwent eccentric remodeling, exhibited by increased left ventricle internal diameter and volumes during systole and diastole, ultimately leading to greater stroke volume. However, we did not find any specific alterations in systolic or diastolic functional measures; nor were there any changes in SERCA activity and its content relative to PLN after Li supplementation. Thus, while Li supplementation appears to positively influence cardiac morphology to increase stroke volume, these changes are independent of changes to SERCA function.

亚治疗性锂补充引起年轻成年野生型雄性小鼠的生理性偏心心肌肥大。
在C57BL/6J野生型(WT)雄性小鼠中,6周的低剂量锂(Li)补充已被证明可以改善心肌sarco(endo)质网钙(Ca2+)- atp酶(SERCA)的活性。在各种啮齿类动物模型中,心肌SERCA功能的改善可导致收缩和舒张功能的改善。在这项研究中,我们验证了12周的亚治疗性Li补充(10mg /kg/天)会增强SERCA功能并对心脏收缩力和形态产生积极影响的假设。在Li治疗的最后一周使用高频超声评估心功能和形态学。随后,在分离的左心室组织上进行SERCA活性、Ca2+摄取测定和糖原合成酶激酶3β、SERCA2及其抑制剂磷蛋白(PLN)的Western blotting。亚治疗性Li补充12周后,心脏发生偏心重塑,表现为收缩和舒张期左心室内径和容积增加,最终导致更大的卒中容积。然而,我们未发现收缩期或舒张期功能指标有任何特异性改变;Li补充后,SERCA活性及其相对于PLN的含量也没有任何变化。因此,虽然Li补充剂似乎对心脏形态有积极影响,增加了卒中容量,但这些变化与SERCA功能的变化无关。
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来源期刊
Physiological Reports
Physiological Reports PHYSIOLOGY-
CiteScore
4.20
自引率
4.00%
发文量
374
审稿时长
9 weeks
期刊介绍: Physiological Reports is an online only, open access journal that will publish peer reviewed research across all areas of basic, translational, and clinical physiology and allied disciplines. Physiological Reports is a collaboration between The Physiological Society and the American Physiological Society, and is therefore in a unique position to serve the international physiology community through quick time to publication while upholding a quality standard of sound research that constitutes a useful contribution to the field.
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