P3742AAV9-mediated delivery of a NFAT decoy oligonucleotide prevents pathological myocardial hypertrophy and heart failure in mice

The purpose of this study was to determine lactate transport kinetics in single isolated rat ventricular cardiac myocytes after 1) 8 wk of myocardial volume overload (MVO) and 2) congestive heart failure (CHF). Twenty male Sprague-Dawley rats were assigned to one of four groups: myocardial hypertrophy (MH), MH sham (MHS), CHF, or CHF sham (CHFS). A chronic MVO was induced in the MH and CHF groups by an infrarenal arteriovenous fistula. Postdeath heart and lung weights were significantly greater ( P < 0.05) for the MH and CHF groups compared with controls. Isolated cardiac myocytes were loaded with BCECF to determine intracellular pH (pHi) changes after the addition of lactate to the extracellular superfusate. Alterations in pHi with the addition of varied lactate concentrations were attenuated 72–89% by 5.0 mM α-cyano-4-hydroxycinnamate. Significant differences ( P < 0.05) were found in estimated maximal lactate transport rates between the experimental and sham groups (MH = 19.4 ± 1.1 nmol · μl−1 · min−1vs. MHS = 15.1 ± 1.1 nmol · μl−1 · min−1; CHF = 20.2 ± 2.0 nmol · μl−1 · min−1vs. CHFS = 14.0 ± 0.9 nmol · μl−1 · min−1). Western blot analysis confirmed a 270% increase in monocarboxylate symport protein 1 (MCT1) protein content in CHF compared with CHFS rats. The results of this study suggest that MH and CHF induced by MVO engender a greater maximal lactate transport capacity across the cardiac myocyte sarcolemma along with an increase in MCT1 protein content. These alterations would likely benefit the cell by attenuating intracellular acidification during a period of increased myocardial load.

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Diurnal physiology: core principles with application to the pathogenesis, diagnosis, prevention, and treatment of myocardial hypertrophy and failure

Journal of Applied Physiology ◽

10.1152/japplphysiol.00426.2009 ◽

2009 ◽

Vol 107 (4) ◽

pp. 1318-1327 ◽

Cited By ~ 31

Author(s):

Michael J. Sole ◽

Tami A. Martino

Keyword(s):

Heart Failure ◽

Myocardial Hypertrophy ◽

Daily Variation ◽

Normal Growth ◽

Circadian System ◽

Growth And Remodeling ◽

Treatment And Prevention ◽

Cardiovascular Tissues ◽

Daily Rhythmicity ◽

Health And Disease

The circadian system has been shown to be fundamentally important in human health and disease. Recently, there have been major advances in our understanding of daily rhythmicity, and its relevance to human physiology, and to the pathogenesis and treatment of cardiac hypertrophy and heart failure. Cardiovascular tissues, such as heart and blood vessels, show remarkable daily variation in gene expression, metabolism, growth, and remodeling. Moreover, synchrony of daily molecular and physiological rhythms is integral to healthy organ growth and renewal. Disruption of these rhythms adversely affects normal growth, also the remodeling mechanisms in disease, leading to gross abnormalities in heart and vessels. These observations provide new insights into the pathogenesis, diagnosis, treatment, and prevention of heart disease. In this review, we focus on the recent advances in circadian biology and cardiovascular function, with particular emphasis on how this applies to human myocardial hypertrophy and heart failure, and the implications and importance for translational medicine.

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