Sophie I Hamstra, Mia S Geromella, Peter Tiidus, Panagiota Klentrou, Rebecca E K MacPherson, Val A Fajardo
{"title":"Subtherapeutic lithium supplementation causes physiological eccentric cardiac hypertrophy in young-adult wild-type male mice.","authors":"Sophie I Hamstra, Mia S Geromella, Peter Tiidus, Panagiota Klentrou, Rebecca E K MacPherson, Val A Fajardo","doi":"10.14814/phy2.70299","DOIUrl":null,"url":null,"abstract":"<p><p>Six weeks of low-dose lithium (Li) supplementation has been shown to improve the activity of cardiac sarco(endo)plasmic reticulum calcium (Ca<sup>2+</sup>)-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, Ca<sup>2+</sup> 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.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 7","pages":"e70299"},"PeriodicalIF":2.2000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962211/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Physiological Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14814/phy2.70299","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
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.
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.