Brandon J Biesiadecki

The Ohio State University, Columbus, Ohio, United States

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Publications (39)170.55 Total impact

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    ABSTRACT: -While sinoatrial node (SAN) dysfunction is a hallmark of human heart failure (HF), the underlying mechanisms remain poorly understood. We aimed to examine the role of adenosine in SAN dysfunction and tachy-brady arrhythmias in chronic HF.
    Circulation 05/2014; · 15.20 Impact Factor
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    ABSTRACT: Repeated, intense contractile activity compromises the ability of skeletal muscle to generate force and velocity, resulting in fatigue. The decrease in velocity is thought to be due, in part, to the intracellular build-up of acidosis inhibiting the function of the contractile proteins myosin and troponin, however the underlying molecular basis of this process remains poorly understood. We sought to gain novel insight into the decrease in velocity by determining if the depressive effect of acidosis could be altered by 1) introducing Ca(++)-sensitizing mutations into troponin (Tn) or 2) by agents that directly affect myosin function, including inorganic phosphate (Pi) and 2-deoxy-ATP (dATP) in an in vitro motility assay. Acidosis reduced regulated thin filament velocity (VRTF) at both maximal and sub-maximal Ca(++) levels in a pH-dependent manner. A truncated construct of the inhibitory subunit of troponin (TnI) and a Ca(++)-sensitizing mutation in the Ca(++)-binding subunit of troponin (TnC) increased VRTF at sub-maximal Ca(++) under acidic conditions, but had no effect on VRTF at maximal Ca(++) levels. In contrast, both Pi and replacement of ATP with dATP reversed much of the acidosis-induced depression of VRTF at saturating Ca(++). Interestingly, despite producing similar magnitude increases in VRTF, the combined effects of Pi and dATP were additive, suggesting different underlying mechanisms of action. These findings suggest that acidosis depresses velocity by slowing the detachment rate from actin but also by possibly slowing the attachment rate.
    Journal of Applied Physiology 03/2014; · 3.48 Impact Factor
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    ABSTRACT: -Hypertrophic cardiomyopathy (HCM) is a common genetic disorder caused mainly by mutations in sarcomeric proteins and is characterized by maladaptive myocardial hypertrophy, diastolic heart failure, increased myofilament Ca(2+) sensitivity and high susceptibility to sudden death. We tested the following hypothesis: correction of the increased myofilament sensitivity can delay or prevent the development of the HCM phenotype. -We used an HCM mouse model with an E180G mutation in α-tropomyosin (Tm180) that demonstrates increased myofilament Ca(2+) sensitivity, severe hypertrophy and diastolic dysfunction. To test our hypothesis, we reduced myofilament Ca(2+) sensitivity in Tm180 mice by generating a double transgenic (DTG) mouse line. We crossed Tm180 mice with mice expressing a pseudo-phosphorylated cardiac troponin I (cTnI) (S23D and S24D; TnI-PP). TnI-PP mice demonstrated a reduced myofilament Ca(2+) sensitivity compared to wild-type mice. The development of pathological hypertrophy did not occur in mice expressing both Tm180 and TnI-PP. Left ventricle performance was improved in DTG compared to their Tm180 littermates, which express wild-type cTnI. Hearts of DTG mice demonstrated no changes in expression of phospholamban (PLN) and Serca2a, increased levels of PLN and TnT phosphorylation, and reduced phosphorylation of TnI compared to Tm180 mice. Moreover, expression of TnI-PP in Tm180 hearts inhibited modifications in the activity of ERK1/2 and GATA-4 in Tm180 hearts. -Our data strongly indicate that reduction of myofilament sensitivity to Ca(2+) and associated correction of abnormal relaxation can delay or prevent development of HCM and should be considered as a therapeutic target for HCM.
    Circulation Cardiovascular Genetics 02/2014; · 6.73 Impact Factor
  • Bin Liu, Joseph J Lopez, Brandon J Biesiadecki, Jonathan P Davis
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    ABSTRACT: Adrenergic stimulation modulates cardiac function by altering the phosphorylation status of several cardiac proteins. The Troponin complex, which is the Ca(2+) sensor for cardiac contraction, is a hot spot for adrenergic phosphorylation. While the effect of β-adrenergic related PKA phosphorylation of troponin I at Ser23/24 is well established, the effects of α-adrenergic induced PKC phosphorylation on multiple sites of TnI (Ser43/45, Thr144) and TnT (Thr194, Ser198, Thr203 and Thr284) are much less clear. By utilizing an IAANS labeled fluorescent troponin C, [Formula: see text], we systematically examined the site specific effects of PKC phosphomimetic mutants of TnI and TnT on TnC's Ca(2+) binding properties in the Tn complex and reconstituted thin filament. The majority of the phosphomemetics had little effect on the Ca(2+) binding properties of the isolated Tn complex. However, when incorporated into the thin filament, the phosphomimetics typically altered thin filament Ca(2+) sensitivity in a way consistent with their respective effects on Ca(2+) sensitivity of skinned muscle preparations. The altered Ca(2+) sensitivity could be generally explained by a change in Ca(2+) dissociation rates. Within TnI, phosphomimetic Asp and Glu did not always behave similar, nor were Ala mutations (used to mimic non-phosphorylatable states) benign to Ca(2+) binding. Our results suggest that Troponin may act as a hub on the thin filament, sensing physiological stimuli to modulate the contractile performance of the heart.
    PLoS ONE 01/2014; 9(1):e86279. · 3.73 Impact Factor
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    ABSTRACT: The binding of Ca2 + to troponin C (TnC) in the troponin complex is a critical step regulating the thin filament, the actin-myosin interaction and cardiac contraction. Phosphorylation of the troponin complex is a key regulatory mechanism to match cardiac contraction to demand. Here we demonstrate phosphorylation of the troponin I (TnI) subunit is simultaneously increased at Ser-150 and Ser-23/24 during in vivo myocardial ischemia. Myocardial ischemia decreases intracellular pH resulting in depressed binding of Ca2 + to TnC and impaired contraction. To determine the pathological relevance of simultaneous TnI phosphorylation we measured individual TnI Ser-150 (S150D), Ser-23/24 (S23/24D) and combined (S23/24/150D) pseudo-phosphorylation effects on thin filament regulation at acidic pH similar to that in myocardial ischemia. Results demonstrate that while acidic pH decreased thin filament Ca2 + binding to TnC regardless of TnI composition, TnI S150D attenuated this decrease rendering it similar to non-phosphorylated TnI at normal pH. The dissociation of Ca2 + from TnC was unaltered by pH such that TnI S150D remained slow, S23/24D remained accelerated and the combined S23/24/150D remained accelerated. This effect of the combined TnI Ser-150 and Ser-23/24 pseudo-phosphorylation to maintain Ca2 + binding while accelerating Ca2 + dissociation represents the first post-translational modification of troponin by phosphorylation to both accelerate thin filament deactivation and maintain Ca2 + sensitive activation. These data suggest TnI Ser-150 phosphorylation attenuation of the pH-dependent decrease in Ca2 + sensitivity and its combination with Ser-23/24 phosphorylation to maintain accelerated thin filament deactivation may impart an adaptive role to preserve contraction during acidic ischemia pH without slowing relaxation.
    Journal of Molecular and Cellular Cardiology 01/2014; · 5.15 Impact Factor
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    ABSTRACT: Recent studies suggest that proarrhythmic effects of cardiac glycosides (CGs) on cardiomyocyte Ca(2+) handling involves generation of reactive oxygen species (ROS). However, the specific pathway(s) of ROS production and the subsequent downstream molecular events that mediate CG-dependent arrhythmogenesis remain to be defined.Methods and ResultsWe examined the effects of digitoxin (DGT) on Ca(2+) handling and ROS production in cardiomyocytes using a combination of pharmacological approaches and genetic mouse models. Myocytes isolated from mice deficient in NADPH oxidase type 2 (NOX2KO) and mice transgenically overexpressing mitochondrial superoxide dismutase displayed markedly increased tolerance to the proarrhythmic action of DGT as manifested by inhibition of DGT-dependent ROS and spontaneous Ca(2+) waves (SCW). Additionally, DGT-induced mitochondrial membrane potential depolarization was abolished in NOX2KO cells. DGT-dependent ROS was suppressed by inhibition of PI3K, PKC and the mitochondrial KATP channel, suggesting roles for these proteins, respectively, in activation of NOX2 and in mitochondrial ROS generation. Western blot revealed increased levels of oxidized CaMKII in WT but not in NOX2KO hearts treated with DGT. The DGT-induced increase in SCW frequency was abolished in myocytes isolated from mice in which the Ser 2814 CaMKII phosphorylation site on RyR2 is constitutively inactivated. These results suggest that the arrhythmogenic adverse effects of CGs on Ca(2+) handling involve PI3K- and PKC-mediated stimulation of NOX2 and subsequent NOX2-dependent ROS release from the mitochondria; mitochondria-derived ROS then activate CaMKII with consequent phosphorylation of RyR2 at Ser 2814.
    Cardiovascular research 10/2013; · 5.81 Impact Factor
  • Laurin M Hanft, Brandon J Biesiadecki, Kerry S McDonald
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    ABSTRACT: According to the Frank-Starling relationship, greater end diastolic volume increases ventricular output. The Frank-Starling relationship is based, in part, on the length-tension relationship in cardiac myocytes. Recently, we identified a dichotomy in the steepness of length-tension relationships in mammalian cardiac myocytes that was dependent upon PKA-induced myofibrillar phosphorylation. Since PKA has multiple myofibrillar substrates including titin, myosin binding protein-C (MyBP-C), and cardiac troponin I (cTnI), we sought to define if phosphorylation of one of these molecules could control length-tension relationships. We focused on cTnI since troponin can be exchanged in permeabilized striated muscle cell preparations and tested the hypothesis that phosphorylation of cTnI modulates length dependence of force generation. For these experiments, we exchanged unphosphorylated recombinant cardiac troponin (cTn) into either a rat cardiac myocyte preparation or a skinned slow-twitch skeletal muscle fibre. In all cases unphosphorylated cTn yielded a shallow length-tension relationship, which was shifted to a steep relationship after PKA treatment. Furthermore, exchange with cTn having cTnI serines 23 and 24 mutated to aspartic acids to mimic phosphorylation always shifted a shallow length-tension relationship to a steep relationship. Overall, these results indicate that phosphorylation of cTnI serines 23/24 is a key regulator of length dependence of force generation in striated muscle.
    The Journal of Physiology 07/2013; · 4.38 Impact Factor
  • Mark T Ziolo, Brandon J Biesiadecki
    Journal of Molecular and Cellular Cardiology 06/2013; · 5.15 Impact Factor
  • Biophysical Journal 01/2013; 104(2):450-. · 3.67 Impact Factor
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    ABSTRACT: Tropomyosin (Tm) is a central protein in the Ca(2+) regulation of striated muscle. The αTm isoform undergoes phosphorylation at serine residue 283. While the biochemical and steady-state muscle function of muscle purified Tm phosphorylation have been explored, the effects of Tm phosphorylation on the dynamic properties of muscle contraction and relaxation are unknown. To investigate the kinetic regulatory role of αTm phosphorylation we expressed and purified native N-terminal acetylated Ser-283 wild-type, S283A phosphorylation null and S283D pseudo-phosphorylation Tm mutants from insect cells. Purified Tm's regulate thin filaments similar to that reported for muscle purified Tm. Steady-state Ca(2+) binding to troponin C (TnC) in reconstituted thin filaments did not differ between the 3 Tm's, however disassociation of Ca(2+) from filaments containing pseudo-phosphorylated Tm was slowed compared to WT Tm. Replacement of pseudo-phosphorylated Tm into myofibrils similarly prolonged the slow phase of relaxation and decreased the rate of the fast phase without altering activation kinetics. These data demonstrate that Tm pseudo-phosphorylation slows deactivation of the thin filament and muscle force relaxation dynamics in the absence of dynamic and steady-state effects on muscle activation. This supports a role for Tm as a key protein in the regulation of muscle relaxation dynamics.
    Archives of Biochemistry and Biophysics 12/2012; · 3.37 Impact Factor
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    ABSTRACT: We have previously shown that the main factor responsible for the faster [Ca(2+)](i) decline rate with β-adrenergic (β-AR) stimulation is the phosphorylation of phospholamban (PLB) rather than the increase in systolic Ca(2+) levels. The purpose of this study was to correlate the extent of augmentation of PLB Serine(16) phosphorylation to the rate of [Ca(2+)](i) decline. Thus, ventricular myocytes were isolated from neuronal nitric oxide synthase knockout (NOS1(-/-)) mice, which we observed had lower basal PLB Serine(16) phosphorylation levels, but equal levels during β-AR stimulation. Ca(2+) transients (Fluo-4) were measured in myocytes superfused with 3mM extracellular Ca(2+) ([Ca(2+)](o)) and a non-specific β-AR agonist isoproterenol (ISO, 1μM) with 1mM [Ca(2+)](o). This allowed us to get matched Ca(2+) transient amplitudes in the same myocyte. Similar to our previous work, Ca(2+) transient decline was significantly faster with ISO compared to 3mM [Ca(2+)](o), even with matched Ca(2+) transient amplitudes. Interestingly, when we compared the effects of ISO on Ca(2+) transient decline between NOS1(-/-) and WT myocytes, ISO had a larger effect in NOS1(-/-) myocytes, which resulted in a greater percent decrease in the Ca(2+) transient RT(50). We believe this is due to a greater augmentation of PLB Serine16 phosphorylation in these myocytes. Thus, our results suggest that not only the amount but the extent of augmentation of PLB Serine(16) phosphorylation are the major determinants for the Ca(2+) decline rate. Furthermore, our data suggest that the molecular mechanisms of Ca(2+) transient decline is normal in NOS1(-/-) myocytes and that the slow basal Ca(2+) transient decline is predominantly due to decreased PLB phosphorylation.
    Nitric Oxide 08/2012; 27(4):242-7. · 3.27 Impact Factor
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    ABSTRACT: Hydroxyl radicals (OH) are involved in the pathogenesis of reperfusion injury and are observed in acute heart failure, stroke, and myocardial infarction. Two different subcellular defects are involved in the pathogenesis of OH injury, deranged calcium handling, and alterations of myofilament responsiveness, but their temporal impact on contractile function is not resolved. Initially, after brief OH exposure, there is a corresponding marked increase in diastolic calcium and diastolic force. We followed these parameters until a new steady-state level was reached at ∼45 min post-OH exposure. At this new baseline, diastolic calcium had returned to near-normal, pre-OH levels, whereas diastolic force remained markedly elevated. An increased calcium sensitivity was observed at the new baseline after OH-induced injury compared with the pre-OH state. The acute injury that occurs after OH exposure is mainly due to calcium overload, while the later sustained myocardial dysfunction is mainly due to the altered/increased myofilament responsiveness.
    Journal of Applied Physiology 07/2012; 113(5):766-74. · 3.48 Impact Factor
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    ABSTRACT: The rate-limiting step of cardiac muscle relaxation has been proposed to reside in the myofilament. Both the rates of cross-bridge detachment and Ca(2+) dissociation from troponin C (TnC) have been hypothesized to rate-limit myofilament inactivation. In this study we used a fluorescent TnC to measure both the rate of Ca(2+) dissociation from TnC and the rate of cross-bridge detachment from several different species of ventricular myofibrils. The fluorescently labeled TnC was sensitive to both Ca(2+) dissociation and cross-bridge detachment at low Ca(2+) (presence of EGTA), allowing for a direct comparison between the two proposed rates of myofilament inactivation. Unlike Ca(2+) dissociation from TnC, cross-bridge detachment varied in myofibrils from different species and was rate-limited by ADP release. At subphysiological temperatures (<20 °C), the rate of Ca(2+) dissociation from TnC was faster than the rate of cross-bridge detachment in the presence of ADP. These results support the hypothesis that cross-bridge detachment rate-limits relaxation. However, Ca(2+) dissociation from TnC was not as temperature-sensitive as cross-bridge detachment. At a near physiological temperature (35 °C) and ADP, the rate of cross-bridge detachment may actually be faster than the rate of Ca(2+) dissociation. This provides evidence that there may not be a simple, single rate-limiting step of myofilament inactivation.
    Journal of Biological Chemistry 06/2012; 287(33):27930-40. · 4.65 Impact Factor
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    ABSTRACT: Aberrant myofilament Ca(2+) sensitivity is commonly observed with multiple cardiac diseases, especially familial cardiomyopathies. Although the etiology of the cardiomyopathies remains unclear, improving cardiac muscle Ca(2+) sensitivity through either pharmacological or genetic approaches shows promise of alleviating the disease-related symptoms. Due to its central role as the Ca(2+) sensor for cardiac muscle contraction, troponin C (TnC) stands out as an obvious and versatile target to reset disease-associated myofilament Ca(2+) sensitivity back to normal. To test the hypothesis that aberrant myofilament Ca(2+) sensitivity and its related function can be corrected through rationally engineered TnC constructs, three thin filament protein modifications representing different proteins (troponin I or troponin T), modifications (missense mutation, deletion, or truncation), and disease subtypes (familial or acquired) were studied. A fluorescent TnC was utilized to measure Ca(2+) binding to TnC in the physiologically relevant biochemical model system of reconstituted thin filaments. Consistent with the pathophysiology, the restrictive cardiomyopathy mutation, troponin I R192H, and ischemia-induced truncation of troponin I (residues 1-192) increased the Ca(2+) sensitivity of TnC on the thin filament, whereas the dilated cardiomyopathy mutation, troponin T ΔK210, decreased the Ca(2+) sensitivity of TnC on the thin filament. Rationally engineered TnC constructs corrected the abnormal Ca(2+) sensitivities of the thin filament, reconstituted actomyosin ATPase activity, and force generation in skinned trabeculae. Thus, the present study provides a novel and versatile therapeutic strategy to restore diseased cardiac muscle Ca(2+) sensitivity.
    Journal of Biological Chemistry 04/2012; 287(24):20027-36. · 4.65 Impact Factor
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    ABSTRACT: AMP-activated protein kinase (AMPK) is an energy-sensing enzyme central to the regulation of metabolic homeostasis. In the heart AMPK is activated during cardiac stress-induced ATP depletion and functions to stimulate metabolic pathways that restore the AMP/ATP balance. Recently it was demonstrated that AMPK phosphorylates cardiac troponin I (cTnI) at Ser-150 in vitro. We sought to determine if the metabolic regulatory kinase AMPK phosphorylates cTnI at Ser-150 in vivo to alter cardiac contractile function directly at the level of the myofilament. Rabbit cardiac myofibrils separated by two-dimensional isoelectric focusing subjected to a Western blot with a cTnI phosphorylation-specific antibody demonstrates that cTnI is endogenously phosphorylated at Ser-150 in the heart. Treatment of myofibrils with the AMPK holoenzyme increased cTnI Ser-150 phosphorylation within the constraints of the muscle lattice. Compared with controls, cardiac fiber bundles exchanged with troponin containing cTnI pseudo-phosphorylated at Ser-150 demonstrate increased sensitivity of calcium-dependent force development, blunting of both PKA-dependent calcium desensitization, and PKA-dependent increases in length dependent activation. Thus, in addition to the defined role of AMPK as a cardiac metabolic energy gauge, these data demonstrate AMPK Ser-150 phosphorylation of cTnI directly links the regulation of cardiac metabolic demand to myofilament contractile energetics. Furthermore, the blunting effect of cTnI Ser-150 phosphorylation cross-talk can uncouple the effects of myofilament PKA-dependent phosphorylation from β-adrenergic signaling as a novel thin filament contractile regulatory signaling mechanism.
    Journal of Biological Chemistry 04/2012; 287(23):19136-47. · 4.65 Impact Factor
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    ABSTRACT: Numerous studies have aimed to elucidate markers for the onset of decompensatory hypertrophy and heart failure in vivo and in vitro. Alterations in the force-frequency relationship are commonly used as markers for heart failure with a negative staircase being a hallmark of decompensated cardiac function. Here we aim to determine the functional and molecular alterations in the very early stages of compensatory hypertrophy through analysis of the force-frequency relationship, using a novel isolated muscle culture system that allows assessment of force-frequency relationship during the development of hypertrophy. New Zealand white male rabbit trabeculae excised from the right ventricular free wall were utilized for all experiments. Briefly, muscles held at constant preload and contracting isometrically were stimulated to contract in culture for 24 h, and in a subset up to 48 h. We found that, upon an increase in the preload and maintaining the muscles in culture for up to 24 h, there was an increase in baseline force produced by isolated trabeculae over time. This suggests a gradual compensatory response to the impact of increased preload. Temporal analysis of the force-frequency response during this progression revealed a significant blunting (at 12 h) and then reversal of the positive staircase as culture time increased (at 24 h). Phosphorylation analysis revealed a significant decrease in desmin and troponin (Tn)I phosphorylation from 12 to 24 h in culture. These results show that even very early on in the compensatory hypertrophy state, the force-frequency relationship is already affected. This effect on force-frequency relationship may, in addition to protein expression changes, be partially attributed to the alterations in myofilament protein phosphorylation.
    AJP Heart and Circulatory Physiology 03/2012; 302(12):H2509-17. · 4.01 Impact Factor
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    ABSTRACT: Myofilament calcium sensitivity decreases with frequency in intact healthy rabbit trabeculae and associates with Troponin I and Myosin light chain-2 phosphorylation. We here tested whether serine-threonine kinase activity is primarily responsible for this frequency-dependent modulations of myofilament calcium sensitivity. Right ventricular trabeculae were isolated from New Zealand White rabbit hearts and iontophoretically loaded with bis-fura-2. Twitch force-calcium relationships and steady state force-calcium relationships were measured at frequencies of 1 and 4 Hz at 37 °C. Staurosporine (100 nM), a nonspecific serine-threonine kinase inhibitor, or vehicle (DMSO) was included in the superfusion solution before and during the contractures. Staurosporine had no frequency-dependent effect on force development, kinetics, calcium transient amplitude, or rate of calcium transient decline. The shift in the pCa(50) of the force-calcium relationship was significant from 6.05 ± 0.04 at 1 Hz versus 5.88 ± 0.06 at 4 Hz under control conditions (vehicle, P < 0.001) but not in presence of staurosporine (5.89 ± 0.08 at 1 Hz versus 5.94 ± 0.07 at 4 Hz, P = NS). Phosphoprotein analysis (Pro-Q Diamond stain) confirmed that staurosporine significantly blunted the frequency-dependent phosphorylation at Troponin I and Myosin light chain-2. We conclude that frequency-dependent modulation of calcium sensitivity is mediated through a kinase-specific effect involving phosphorylation of myofilament proteins.
    Biochemistry research international. 01/2012; 2012:290971.
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    ABSTRACT: Diabetic heart disease is a distinct clinical entity that can progress to heart failure and sudden death. However, the mechanisms responsible for the alterations in excitation-contraction coupling leading to cardiac dysfunction during diabetes are not well known. Hyperglycemia, the landmark of diabetes, leads to the formation of advanced glycation end products (AGEs) on long-lived proteins, including sarcoplasmic reticulum (SR) Ca(2+) regulatory proteins. However, their pathogenic role on SR Ca(2+) handling in cardiac myocytes is unknown. Therefore, we investigated whether an AGE cross-link breaker could prevent the alterations in SR Ca(2+) cycling that lead to in vivo cardiac dysfunction during diabetes. Streptozotocin-induced diabetic rats were treated with alagebrium chloride (ALT-711) for 8 weeks and compared to age-matched placebo-treated diabetic rats and healthy rats. Cardiac function was assessed by echocardiographic examination. Ventricular myocytes were isolated to assess SR Ca(2+) cycling by confocal imaging and quantitative Western blots. Diabetes resulted in in vivo cardiac dysfunction and ALT-711 therapy partially alleviated diastolic dysfunction by decreasing isovolumetric relaxation time and myocardial performance index (MPI) (by 27 and 41% vs. untreated diabetic rats, respectively, P < 0.05). In cardiac myocytes, diabetes-induced prolongation of cytosolic Ca(2+) transient clearance by 43% and decreased SR Ca(2+) load by 25% (P < 0.05); these parameters were partially improved after ALT-711 therapy. SERCA2a and RyR2 protein expression was significantly decreased in the myocardium of untreated diabetic rats (by 64 and 36% vs. controls, respectively, P < 0.05), but preserved in the treated diabetic group compared to controls. Collectively, our results suggest that, in a model of type 1 diabetes, AGE accumulation primarily impairs SR Ca(2+) reuptake in cardiac myocytes and that long-term treatment with an AGE cross-link breaker partially normalized SR Ca(2+) handling and improved diabetic cardiomyopathy.
    Frontiers in Physiology 01/2012; 3:292.
  • Biophysical Journal 01/2012; 102(3):555-. · 3.67 Impact Factor
  • Laurin M. Hanft, Brandon J. Biesiadecki, Kerry S. McDonald
    Biophysical Journal 01/2012; 102(3):556-. · 3.67 Impact Factor

Publication Stats

367 Citations
170.55 Total Impact Points

Institutions

  • 2010–2014
    • The Ohio State University
      • Department of Physiology and Cell Biology
      Columbus, Ohio, United States
  • 2007–2010
    • University of Illinois at Chicago
      • • Department of Medicine (Chicago)
      • • Department of Physiology and Biophysics (Chicago)
      Chicago, IL, United States
    • Case Western Reserve University School of Medicine
      • Department of Physiology and Biophysics
      Cleveland, Ohio, United States
  • 2002–2007
    • Case Western Reserve University
      • Department of Physiology and Biophysics
      Cleveland, OH, United States