%0 Journal Article %1 Pies_2002_I63 %A Pieske, Burkert %A Maier, Lars S %A Schmidt-Schweda, Stephan %D 2002 %J Basic Res. Cardiol. %K 12479237 ATPase, Calcium, Calcium-Binding Cardiac Contraction, Gov't, Heart, Humans, In Low, Myocardial Non-U.S. Output, Proteins, Reference Research Rest, Reticulum, Sarcoplasmic Support, Values, Vitro, {C}a$^{2+}$-Transporting %P I63--I71 %T Sarcoplasmic reticulum Ca$^2+$ load in human heart failure. %V 97 Suppl 1 %X Excitation-contraction coupling and intracellular Ca$^2+$ homeostasis are altered in heart failure. We tested the hypothesis that these changes are related to disturbed Ca$^2+$ handling of the sarcoplasmic reticulum (SR). Isolated, electrically stimulated trabeculae were obtained from end-stage failing (NYHA IV) and nonfailing human hearts. Isometric twitch tension, intracellular Ca$^2+$ transients (aequorin method) and SR Ca$^2+$ content (rapid cooling contractures) were assessed under basal conditions (1 Hz, 37 degrees C) as well as after stepwise increasing rest intervals from 2-240 s (post-rest contractions). Protein expression of SERCA2a and phospholamban (Western blot) was assessed in a subset of failing trabeculae. In addition, the effects of SERCA1 overexpression on contractile function of isolated myocytes was tested. On average, post-rest twitch tension continuously increased with increasing rest intervals in nonfailing, but declined with rest intervals longer than 15 s in failing myocardium. The rest-dependent contractile changes were accompanied by parallel changes in intracellular Ca$^2+$ transients. Failing trabeculae (n = 40) were grouped (group A: post-rest potentiation (force of contraction > pre-rest twitch force) after 120 s rest interval; group B: post-rest decay (force of contraction < pre-rest twitch force) after 120 s rest interval), and post-rest contractile function was related to SERCA2a and PLB expression. While PLB protein expression was not different, SERCA2a protein expression as well as SERCA2a/PLB ratio was significantly higher in group A vs. group B. Transfection of SERCA1 increased shortening amplitude and enhanced relaxation kinetics in failing human myocytes. In conclusion, SR Ca$^2+$ handling is severely altered in human heart failure. Reduced SR Ca$^2+$ release is due to diminished SR Ca$^2+$ content directly related to a depressed expression of SERCA2a protein. Enhancing SERCA function or expression may improve SR Ca$^2+$ handling in failing human myocardium.

@article{Pies_2002_I63, abstract = {Excitation-contraction coupling and intracellular {C}a$^{2+}$ homeostasis are altered in heart failure. We tested the hypothesis that these changes are related to disturbed {C}a$^{2+}$ handling of the sarcoplasmic reticulum (SR). Isolated, electrically stimulated trabeculae were obtained from end-stage failing ({NYHA} {IV}) and nonfailing human hearts. Isometric twitch tension, intracellular {C}a$^{2+}$ transients (aequorin method) and SR {C}a$^{2+}$ content (rapid cooling contractures) were assessed under basal conditions (1 Hz, 37 degrees C) as well as after stepwise increasing rest intervals from 2-240 s (post-rest contractions). Protein expression of SERCA2a and phospholamban (Western blot) was assessed in a subset of failing trabeculae. In addition, the effects of SERCA1 overexpression on contractile function of isolated myocytes was tested. On average, post-rest twitch tension continuously increased with increasing rest intervals in nonfailing, but declined with rest intervals longer than 15 s in failing myocardium. The rest-dependent contractile changes were accompanied by parallel changes in intracellular {C}a$^{2+}$ transients. Failing trabeculae (n = 40) were grouped (group A: post-rest potentiation (force of contraction > pre-rest twitch force) after 120 s rest interval; group B: post-rest decay (force of contraction < pre-rest twitch force) after 120 s rest interval), and post-rest contractile function was related to SERCA2a and PLB expression. While PLB protein expression was not different, SERCA2a protein expression as well as SERCA2a/PLB ratio was significantly higher in group A vs. group B. Transfection of SERCA1 increased shortening amplitude and enhanced relaxation kinetics in failing human myocytes. In conclusion, SR {C}a$^{2+}$ handling is severely altered in human heart failure. Reduced SR {C}a$^{2+}$ release is due to diminished SR {C}a$^{2+}$ content directly related to a depressed expression of SERCA2a protein. Enhancing SERCA function or expression may improve SR {C}a$^{2+}$ handling in failing human myocardium.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Pieske, Burkert and Maier, Lars S and Schmidt-Schweda, Stephan}, biburl = {https://www.bibsonomy.org/bibtex/2b51c38e0f7918834315ff99343a0dd68/hake}, description = {The whole bibliography file I use.}, file = {Pies_2002_I63.pdf:Pies_2002_I63.pdf:PDF}, interhash = {f621e70f7b268a726f85345635d680f8}, intrahash = {b51c38e0f7918834315ff99343a0dd68}, journal = {Basic Res. Cardiol.}, keywords = {12479237 ATPase, Calcium, Calcium-Binding Cardiac Contraction, Gov't, Heart, Humans, In Low, Myocardial Non-U.S. Output, Proteins, Reference Research Rest, Reticulum, Sarcoplasmic Support, Values, Vitro, {C}a$^{2+}$-Transporting}, pages = {I63--I71}, pmid = {12479237}, timestamp = {2009-06-03T11:21:25.000+0200}, title = {Sarcoplasmic reticulum {C}a$^{2+}$ load in human heart failure.}, volume = {97 Suppl 1}, year = 2002 }