Published online before print July 31, 2003, doi: 10.1161/01.RES.0000088785.24381.2F
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2003 American Heart Association, Inc.
Integrative Physiology |
Cardiac Memory Is Associated With Decreased Levels of the Transcriptional Factor CREB Modulated by Angiotensin II and Calcium
From the Departments of Pharmacology, Pediatrics and Anesthesiology, Center for Molecular Therapeutics; College of Physicians and Surgeons of Columbia University, New York, NY.
Correspondence to Michael R. Rosen, MD, Gustavus A. Pfeiffer Professor of Pharmacology, Professor of Pediatrics, Director, Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, 630 W 168 St, PH7West-321, New York, NY 10032. E-mail mrr1{at}columbia.edu
Cardiac memory (CM) has short- (STCM) and long-term (LTCM) components modulated by calcium and angiotensin II. LTCM is associated with reduced Ito and Kv4.3 mRNA levels. Because the cAMP response element binding protein, CREB, contributes to CNS memory transcription, we hypothesized that it might be a transcriptional factor in CM, influenced by calcium and angiotensin II. We studied STCM in dogs that were AV sequentially paced (AVP) for 2 hours or sham-operated. STCM was evaluated with ECG and vectorcardiogram (VCG), and subepicardial biopsies were taken at 5 to 120 minutes and investigated for CREB. LTCM was studied in dogs paced for 3 weeks and in sham controls. At 3 weeks the heart was excised, biopsies obtained, and CRE binding tested. STCM induction occurred in AVP dogs but not in sham or AVP dogs treated with saralasin or nifedipine. Nuclear CREB was significantly decreased at 2 hours in the AVP no-drug group only. LTCM dogs manifested reduced binding of nuclear proteins to CRE, and CRE binding activity in the promoter region of Kv4.3. In conclusion, there is an association between STCM induction and decreased nuclear CREB that is angiotensin-modulated and calcium-dependent. Moreover, the decreased CRE binding after 3 weeks of AVP combined with CRE binding activity in the Kv4.3 promoter can explain the Kv4.3 mRNA and Ito downregulation that characterize LTCM.
Key Words: ventricular pacing • CREB • transcription factors • cardiac memory • remodeling
This article has been cited by other articles:
 |
|
 |
|
  D. Jeyaraj, L. D. Wilson, J. Zhong, C. Flask, J. E. Saffitz, I. Deschenes, X. Yu, and D. S. Rosenbaum Mechanoelectrical Feedback as Novel Mechanism of Cardiac Electrical Remodeling Circulation, June 26, 2007; 115(25): 3145 - 3155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Coronel, T. Opthof, A. N. Plotnikov, F. J.G. Wilms-Schopman, I. N. Shlapakova, P. Danilo Jr., E. A. Sosunov, E. P. Anyukhovsky, M. J. Janse, and M. R. Rosen Long-term cardiac memory in canine heart is associated with the evolution of a transmural repolarization gradient Cardiovasc Res, June 1, 2007; 74(3): 416 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-T. Tsai, D. L. Wang, W.-P. Chen, J.-J. Hwang, C.-S. Hsieh, K.-L. Hsu, C.-D. Tseng, L.-P. Lai, Y.-Z. Tseng, F.-T. Chiang, et al. Angiotensin II Increases Expression of {alpha}1C Subunit of L-Type Calcium Channel Through a Reactive Oxygen Species and cAMP Response Element-Binding Protein-Dependent Pathway in HL-1 Myocytes Circ. Res., May 25, 2007; 100(10): 1476 - 1485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hahn, P. H. M. Kullmann, J. P. Horn, and E. S. Levitan D2 autoreceptors chronically enhance dopamine neuron pacemaker activity. J. Neurosci., May 10, 2006; 26(19): 5240 - 5247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ichiki Role of cAMP Response Element Binding Protein in Cardiovascular Remodeling: Good, Bad, or Both? Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 449 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Patberg, M. N. Obreztchikova, S. F. Giardina, A. J. Symes, A. N. Plotnikov, J. Qu, P. Chandra, D. McKinnon, S. R. Liou, A. V. Rybin, et al. The cAMP response element binding protein modulates expression of the transient outward current: Implications for cardiac memory Cardiovasc Res, November 1, 2005; 68(2): 259 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-m. Hwang, T. Y. Kim, and K. J. Lee From The Cover: Complex-periodic spiral waves in confluent cardiac cell cultures induced by localized inhomogeneities PNAS, July 19, 2005; 102(29): 10363 - 10368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Spragg, F. G. Akar, R. H. Helm, R. S. Tunin, G. F. Tomaselli, and D. A. Kass Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts Cardiovasc Res, July 1, 2005; 67(1): 77 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Shvilkin, K. K.L. Ho, M. R. Rosen, and M. E. Josephson T-Vector Direction Differentiates Postpacing From Ischemic T-Wave Inversion in Precordial Leads Circulation, March 1, 2005; 111(8): 969 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-J. Cha, J. R. Ehrlich, L. Zhang, and S. Nattel Atrial Ionic Remodeling Induced by Atrial Tachycardia in the Presence of Congestive Heart Failure Circulation, September 21, 2004; 110(12): 1520 - 1526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rosati and D. McKinnon Regulation of Ion Channel Expression Circ. Res., April 16, 2004; 94(7): 874 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Cerbai and A. Mugelli Angiotensin AT2 receptor: the younger sibling attracts attention Cardiovasc Res, April 1, 2004; 62(1): 7 - 8. [Full Text] [PDF]
|
|
|
|
|
|
K. W. Patberg and M. R. Rosen On the Role of the cAMP Response Element Binding Protein in Long-Term Cardiac Memory Circ. Res., October 31, 2003; 93 (9): e87 - e87. [Full Text] [PDF]
|
|
|
|
|
|
E. J. Folco, K. Roder, G. F. Mitchell, and G. Koren "Cardiac Memory": A Struggle Against Forgetting Circ. Res., September 5, 2003; 93(5): 384 - 386. [Full Text] [PDF]
|
|