Etiology-Dependent Impairment of Diastolic Cardiomyocyte Calcium Homeostasis in Heart Failure With Preserved Ejection Fraction
Autor: | Peter P. Jones, Gustavo Jose Justo da Silva, Einar Sjaastad Norden, Lars Gullestad, Emil K. S. Espe, Ornella Manfra, Fouad A. Zouein, Åsmund T. Røe, Ida G. Lunde, Isabelle van Hout, Michael Frisk, Xin Shen, Yufeng Hou, Christopher Le, Martin Laasmaa, Sean Coffey, Christen P. Dahl, Raffaele Altara, Theis Tønnessen, Alessandro Cataliotti, Ivar Sjaastad, Regis R. Lambert, William E. Louch, J. Magnus Aronsen |
---|---|
Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Diastole Concentric hypertrophy 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Internal medicine Medicine Homeostasis Humans Myocytes Cardiac 030212 general & internal medicine Aged Calcium metabolism Aged 80 and over Heart Failure Diastolic Ejection fraction business.industry Middle Aged medicine.disease Pathophysiology Echocardiography Heart failure Cardiology Calcium Female Cardiology and Cardiovascular Medicine Heart failure with preserved ejection fraction business |
Zdroj: | Journal of the American College of Cardiology |
ISSN: | 1558-3597 0735-1097 |
Popis: | Background Whereas heart failure with reduced ejection fraction (HFrEF) is associated with ventricular dilation and markedly reduced systolic function, heart failure with preserved ejection fraction (HFpEF) patients exhibit concentric hypertrophy and diastolic dysfunction. Impaired cardiomyocyte Ca2+ homeostasis in HFrEF has been linked to disruption of membrane invaginations called t-tubules, but it is unknown if such changes occur in HFpEF. Objectives This study examined whether distinct cardiomyocyte phenotypes underlie the heart failure entities of HFrEF and HFpEF. Methods T-tubule structure was investigated in left ventricular biopsies obtained from HFrEF and HFpEF patients, whereas cardiomyocyte Ca2+ homeostasis was studied in rat models of these conditions. Results HFpEF patients exhibited increased t-tubule density in comparison with control subjects. Super-resolution imaging revealed that higher t-tubule density resulted from both tubule dilation and proliferation. In contrast, t-tubule density was reduced in patients with HFrEF. Augmented collagen deposition within t-tubules was observed in HFrEF but not HFpEF hearts. A causative link between mechanical stress and t-tubule disruption was supported by markedly elevated ventricular wall stress in HFrEF patients. In HFrEF rats, t-tubule loss was linked to impaired systolic Ca2+ homeostasis, although diastolic Ca2+ removal was also reduced. In contrast, Ca2+ transient magnitude and release kinetics were largely maintained in HFpEF rats. However, diastolic Ca2+ impairments, including reduced sarco/endoplasmic reticulum Ca2+-ATPase activity, were specifically observed in diabetic HFpEF but not in ischemic or hypertensive models. Conclusions Although t-tubule disruption and impaired cardiomyocyte Ca2+ release are hallmarks of HFrEF, such changes are not prominent in HFpEF. Impaired diastolic Ca2+ homeostasis occurs in both conditions, but in HFpEF, this mechanism for diastolic dysfunction is etiology-dependent. |
Databáze: | OpenAIRE |
Externí odkaz: |