Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure

Circ Res. 1994 Sep;75(3):443-53. doi: 10.1161/01.res.75.3.443.

Abstract

The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances in Ca2+ release and reuptake from the sarcoplasmic reticulum (SR), whereas functional studies of the cardiac Na(+)-Ca2+ exchanger, another important determinant of myocyte homeostasis, are lacking for the failing human heart. Using a cardiac Na(+)-Ca2+ exchanger cDNA recently cloned from a guinea pig cDNA library, we investigated the gene expression of the cardiac Na(+)-Ca2+ exchanger in relation to the SR Ca(2+)-ATPase. Expression of both genes was quantified in left ventricular myocardium from 24 failing human cardiac explants and 7 control heart samples in relation to beta-myosin heavy chain mRNA by slot blot analysis. Compared with patients with nonfailing hearts, patients with dilated cardiomyopathy (DCM, n = 13) showed a 55% increase in Na(+)-Ca2+ exchanger mRNA levels (P < .05 versus control value) and a 41% increase in patients with coronary artery disease (CAD, n = 11). In the same hearts, SR Ca(2+)-ATPase mRNA levels were decreased by 50% in DCM and by 45% in CAD (P < .05 for both versus control value). There was a positive correlation between Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase mRNA levels both in normal and failing human hearts, albeit with different slopes and intercepts of the regression line. The Na(+)-Ca2+ exchanger protein levels as assessed by Western blot analysis and normalized to beta-myosin heavy chain protein were increased in DCM and CAD (P < .05 and P < .01 versus control value, respectively), whereas SR Ca(2+)-ATPase protein levels were reduced (P < .05 for both groups versus control values). Thus, the Na(+)-Ca2+ exchanger gene expression is enhanced in failing human hearts and may, in part, compensate for the depressed SR function with regard to diastolic Ca2+ removal.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Atrial Natriuretic Factor / biosynthesis*
  • Base Sequence
  • Blotting, Western
  • Calcium / metabolism
  • Calcium-Transporting ATPases / biosynthesis
  • Cardiomyopathy, Dilated / metabolism*
  • Carrier Proteins / biosynthesis*
  • Coronary Disease / metabolism*
  • Female
  • Gene Expression*
  • Gene Library
  • Guinea Pigs
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Myocardium / metabolism*
  • Myosins / biosynthesis
  • Oligodeoxyribonucleotides
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Rats
  • Reference Values
  • Restriction Mapping
  • Sarcoplasmic Reticulum / metabolism
  • Sodium / metabolism
  • Sodium-Calcium Exchanger

Substances

  • Carrier Proteins
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Sodium-Calcium Exchanger
  • Atrial Natriuretic Factor
  • Sodium
  • Myosins
  • Calcium-Transporting ATPases
  • Calcium