The enhanced contractility of the phospholamban-deficient mouse heart persists with aging
Abstract
J. P. Slack, I. L. Grupp, R. Dash, D. Holder, A. Schmidt, M. J. Gerst, T. Tamura, C. Tilgmann, P. F. James, R. Johnson, A. M. Gerdes and E. G. Kranias. The Enhanced Contractility of the Phospholamban-deficient Mouse Heart Persists with Aging. Journal of Molecular and Cellular Cardiology (2001) 33, 1031-1040. Phospholamban ablation in the mouse is associated with significant increases in cardiac contractility. To determine whether this hyperdynamic function persists through the aging process, a longitudinal examination of age-matched phospholamban-deficient and wild-type mice was employed. Kaplan-Meier survival curves indicated no significant differences between phospholamban-deficient and wild-type mice over the first year. Examination of cardiac function revealed significant increases in the rates of contraction (+dP/dt) and relaxation (-dP/dt) in phospholamban-deficient hearts compared with their wild-type counterparts at 3, 6, 12, 18 and 24 months of age. Quantitative immunoblotting indicated that the expression levels of the sarcoplasmic reticulum Ca(2+)-ATPase were not altered in wild-type hearts, while they were significantly decreased at 12 months (40%) and 18 months (20%) in phospholamban-deficient hearts. These findings on the persistence of hyperdynamic cardiac function over the long term suggest that phospholamban may constitute an important target for treatment in heart disease.
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PLB knockout mice have enhanced cardiac contractility without affecting lifespan.
“The phospholamban (PLB) knock-out mouse has enhanced cardiac contractility, without affecting life span”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Slack, et al., 2001
Cites
Luo, W., Grupp, I. L., Harrer, J. M., Ponniah, S., Grupp, G., Duffy, J. J., Doetschman, T., & Kranias, E. G. (1994) · Circulation Research · doi:10.1161/01.res.75.3.401 · Cited by 706 · see citing works
Self-citationMinamisawa, S., Hoshijima, M., Chu, G., Ward, C. A., Frank, K. F., Gu, Y., Martone, M. E., Wang, Y., ROSS, J. R., Kranias, E. G., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)81662-1 · Cited by 505 · see citing works
Self-citationKadambi, V. J., Ponniah, S., Harrer, J. M., Hoit, B. D., Dorn, G. W., Walsh, R. A., & Kranias, E. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118446 · Cited by 327 · see citing works
Self-citationMyocardial aging: functional alterations and related cellular mechanisms
Lakatta, E. G., & Yin, F. (1982) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1982.242.6.h927 · Cited by 238 · see citing works
Hoit, B. D., Khoury, S. F., Kranias, E. G., Ball, N. A., & Walsh, R. A. (1995) · Circulation Research · doi:10.1161/01.res.77.3.632 · Cited by 238 · see citing works
Self-citationLompré, A., Lambert, F., Lakatta, E. G., & Schwartz, K. (1991) · Circulation Research · doi:10.1161/01.res.69.5.1380 · Cited by 200 · see citing works
Froehlich, J. P. (1978) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(78)90364-4 · Cited by 198 · see citing works
Sato, Y., Ferguson, D. G., Sako, H., Dorn, G. W., Kadambi, V. J., Yatani, A., Hoit, B. D., Walsh, R. A., & Kranias, E. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.43.28470 · Cited by 195 · see citing works
Self-citationCardiomyopathy induced by cardiac Gs alpha overexpression
Iwase, M., Uechi, M., Vatner, D. E., Asai, K., Shannon, R. P., Kudej, R. K., Wagner, T. E., Wight, D. C., Patrick, T. A., Ishikawa, Y., et al. (1997) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1997.272.1.h585 · Cited by 159 · see citing works
Effects of age on mechanical and electrical performance of rat myocardium
Capasso, J. M., Malhotra, A., Remily, R. M., et al. (1983) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1983.245.1.h72 · Cited by 141 · see citing works
Excitation-contraction in rat myocardium: alterations with adult aging
Wei, J. Y., Spurgeon, H. A., & Lakatta, E. G. (1984) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1984.246.6.h784 · Cited by 135 · see citing works
Human SERCA2a levels correlate inversely with age in senescent human myocardium
Cain, B. S., Meldrum, D. R., Joo, K. S., Wang, J.-F., Meng, X., Cleveland, J. C., Banerjee, A., & Harken, A. H. (1998) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(98)00233-2 · Cited by 129 · see citing works
Phospholamban Gene Dosage Effects in the Mammalian Heart
Luo, W., Wolska, B. M., Grupp, I. L., et al. (1996) · Circulation Research · doi:10.1161/01.res.78.5.839 · Cited by 122 · see citing works
Self-citationEnhanced calcium uptake of cardiac sarcoplasmic reticulum in exercise-trained old rats
Tate, C. A., Taffet, G. E., Hudson, E. K., et al. (1990) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1990.258.2.h431 · Cited by 103 · see citing works
The relative phospholamban and SERCA2 ratio: a critical determinant of myocardial contractility
Koss, K. L., Grupp, I. L., & Kranias, E. G. (1997) · Basic Research in Cardiology · doi:10.1007/bf00794064 · Cited by 98 · see citing works
Self-citationXu, A., & Narayanan, N. (1998) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1998.275.6.h2087 · Cited by 89 · see citing works
Jiang, M. T., Moffat, M. P., & Narayanan, N. (1993) · Circulation Research · doi:10.1161/01.res.72.1.102 · Cited by 87 · see citing works
Maciel, L. M. Z., Polikar, R., Rohrer, D. K., Popovich, B. K., & DILLMANN, W. H. (1990) · Circulation Research · doi:10.1161/01.res.67.1.230 · Cited by 82 · see citing works
Influence of age, growth, and sex on cardiac myocyte size and number in rats
Bai, S., Campbell, S. E., Moore, J. A., Morales, M. C., & Martin Gerdes, A. (1990) · The Anatomical Record · doi:10.1002/ar.1092260210 · Cited by 79 · see citing works
Chronic exercise prevents characteristic age-related changes in rat cardiac contraction
Spurgeon, H. A., Steinbach, M. F., & Lakatta, E. G. (1983) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1983.244.4.h513 · Cited by 77 · see citing works
Noninvasive indexes of cardiac systolic and diastolic function in hyperthyroid and senescent mouse
Taffet, G. E., Hartley, C. J., Wen, X., Pham, T. T. M., Michael, L. H., & Entman, M. L. (1996) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1996.270.6.h2204 · Cited by 74 · see citing works
Normal and hypertrophied senescent rat heart: mechanical and molecular characteristics
BESSE, S., Assayag, P., Delcayre, C., Carré, F., Sl, C., Lecarpentier, Y., & Bernard Swynghedauw, A. (1993) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1993.265.1.h183 · Cited by 72 · see citing works
Tate, C. A., Helgason, T., Hyek, M. F., et al. (1996) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1996.271.1.h68 · Cited by 69 · see citing works
Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart.
Buttrick, P. M., Malhotra, A., Factor, S. M., et al. (1991) · Circulation Research · doi:10.1161/01.res.68.3.645 · Cited by 67 · see citing works
Assayag, P. (1998) · Cardiovascular Research · doi:10.1016/s0008-6363(97)00283-6 · Cited by 66 · see citing works
CaATPase content is lower in cardiac sarcoplasmic reticulum isolated from old rats
Taffet, G. E., & Tate, C. A. (1993) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1993.264.5.h1609 · Cited by 57 · see citing works
Lim, C. C., Liao, R., Varma, N., & Apstein, C. S. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.5.h2083 · Cited by 57 · see citing works
Narayanan, N. (1987) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(87)90073-x · Cited by 52 · see citing works
Age-related differences in effect of exercise training on cardiac muscle function in rats
Li, Y., Lincoln, T., Mendelowitz, D., et al. (1986) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1986.251.1.h12 · Cited by 39 · see citing works
Application of the immunoblot technique for quantitation of protein levels in cardiac homogenates.
HARRER, J., Kiss, E., & Kranias, E. G. (1995) · PubMed · Cited by 35 · see citing works
Self-citationNew method to evaluate myocyte remodeling from formalin-fixed biopsy and autopsy material
Gerdes, A. M., Onodera, T., Tamura, T., Said, S., Bohlmeyer, T. J., Abraham, W. T., & Bristow, M. R. (1998) · Journal of Cardiac Failure · doi:10.1016/s1071-9164(98)90240-8 · Cited by 32 · see citing works
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Phospholamban: a crucial regulator of cardiac contractility
MacLennan, D. H., & Kranias, E. G. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1151 · Cited by 1,088 · see citing works
Self-citationSmall and large animal models in cardiac contraction research: advantages and disadvantages
Milani-Nejad, N., & Janssen, P. M. L. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.007 · Cited by 484 · see citing works
Haghighi, K., Kolokathis, F., Pater, L., Lynch, R. A., Asahi, M., Gramolini, A. O., Fan, G.-C., Tsiapras, D., Hahn, H. S., Adamopoulos, S., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17892 · Cited by 478 · see citing works
Self-citationQin, F., Siwik, D. A., Lancel, S., Zhang, J., Kuster, G. M., Luptak, I., Wang, L., Tong, X., Kang, Y. J., Cohen, R. A., et al. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000184 · Cited by 122 · see citing works
- Authors
- Slack, J. P., Grupp, I. L., Dash, R., Holder, D., Schmidt, A., Gerst, M. J., Tamura, T., Tilgmann, C., James, P. F., Johnson, R., Gerdes, A. M., & Kranias, E. G.
- Affiliations
- University of Cincinnati (US)
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2001-05
- Volume
- 33
- Issue
- 5
- Pages
- 1031-1040
- ISSN
- 0022-2828 (ISSN-L)
- OpenAlex
- W2064705407
- Cited by
- 64
- References
- 31
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 6 · 2013: 2 · 2012: 3
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institutes of Health (5r01hl030696-12, 5p40rr012358-05)
- National Heart, Lung, and Blood Institute (HL26057, HL07382-17, HL 52318, T32HL007382, P50HL052318, HL30696)
- National Center for Research Resources (1P40 RR12358)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- phospholamban, cardiac contractility, aging, sarcoplasmic reticulum Ca2+-ATPase, hypercontractility, cardiac function, heart disease treatment
- MeSH terms
- Phospholamban, Age Factors, Aging, Animals, Calcium-Binding Proteins, Echocardiography, Female, Genotype, Heart, Male, Myocardial Contraction, Myocardium, Time Factors, Immunoblotting, Blotting, Western, Mice
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