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| EXPRESSION OF DIHYDROPYRIDINE RECEPTOR (CA-2+ CHANNEL) AND CALSEQUESTRIN GENES IN THE MYOCARDIUM OF PATIENTS WITH END-STAGE HEART-FAILURE |
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| Author(s): TAKAHASHI T, ALLEN PD, LACRO RV, MARKS AR, DENNIS AR, SCHOEN FJ, GROSSMAN W, MARSH JD, IZUMO S |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 90 Issue: 3 Pages: 927-935 Published: SEP 1992 |
| Times Cited: 148 References: 57 |
| Abstract: Cytoplasmic free calcium ions (Ca2+) play a central role in excitation-contraction coupling of cardiac muscle. Abnormal Ca2+ handling has been implicated in systolic and diastolic dysfunction in patients with end-stage heart failure. The current study tests the hypothesis that expression of genes encoding proteins regulating myocardial Ca2+ homeostasis is altered in human heart failure. We analyzed RNA isolated from the left ventricular (LV) myocardium of 30 cardiac transplant recipients with end-stage heart failure (HF) and five organ donors (normal control), using cDNA probes specific for the cardiac dihydropyridine (DHP) receptor (the alpha-1 subunit of the DHP-sensitive Ca2+ channel) and cardiac calsequestrin of sarcoplasmic reticulum (SR). In addition, abundance of DHP binding sites was assessed by ligand binding techniques (n = 6 each for the patients and normal controls). There was no difference in the level of cardiac calsequestrin mRNA between the HF patients and normal controls. In contrast, the level of mRNA encoding the DHP receptor was decreased by 47% (P < 0.001) in the LV myocardium from the patients with HF compared to the normal controls. The number of DHP binding sites was decreased by 35-48%. As reported previously, expression of the SR Ca2+-ATPase mRNA was also diminished by 50% (P < 0.001) in the HF group. These data suggest that expression of the genes encoding the cardiac DHP receptor and SR Ca2+-ATPase is reduced in the LV myocardium from patients with HF. Altered expression of these genes may be related to abnormal Ca2+ handling in the failing myocardium, contributing to LV systolic and diastolic dysfunction in patients with end-stage heart failure. |
| Document Type: Article |
| Language: English |
Addresses:
1. BETH ISRAEL HOSP, MOLEC MED UNIT, INDURSKY LAB MOLEC CARDIOL, BOSTON, MA 02215 USA
2. BETH ISRAEL HOSP, DIV CARDIOVASC, BOSTON, MA 02215 USA
3. CHILDRENS HOSP, DEPT CARDIOL, BOSTON, MA 02114 USA
4. BRIGHAM & WOMENS HOSP, DEPT ANESTHESIOL, BOSTON, MA 02114 USA
5. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02114 USA
6. BRIGHAM & WOMENS HOSP, DEPT PATHOL, BOSTON, MA 02114 USA
7. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA
8. HARVARD UNIV, SCH MED, DEPT ANESTHESIOL, BOSTON, MA 02114 USA
9. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA
10. CUNY MT SINAI SCH MED, BROOKDALE CTR MOLEC BIOL, NEW YORK, NY 10029 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: JN959 |
| ISSN: 0021-9738 |
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