Altered myocardial Ca2+cycling after left ventricular assist device support in the failing human heart

Chaudhary, Khuram W.; Rossman, Eric I.; Piacentino, Valentino; Kenessey, Ágnes; Weber, Christopher R.; Gaughan, John; Ojamaa, Kaie; Klein, Irwin; Bers, Donald M.; Houser, Steven R.; Margulies, Kenneth B.

doi:10.1016/j.jacc.2004.05.049

Cited by 86 publications

(81 citation statements)

References 37 publications

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“…Thus, we focused our analysis on SERCA and PLB, proteins whose expression is altered in heart failure and which are responsible for the increased Ca 2ϩ sequestration that results in a potentiated contraction after a stimulus delay. 35,38 Consistent with previous studies, we determined that SERCA expression decreased significantly in failing hearts, 32,35,38 whereas CQ and PLB protein did not change. 35,38 After LVAD, SERCA expression recovered, as others have reported.…”

Section: Discussionsupporting

confidence: 90%

Duration of left ventricular assist device support: Effects on abnormal calcium cycling and functional recovery in the failing human heart

Ogletree

Sweet

Talerico

et al. 2010

The Journal of Heart and Lung Transplantation

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Section: Discussionsupporting

confidence: 90%

Duration of left ventricular assist device support: Effects on abnormal calcium cycling and functional recovery in the failing human heart

Ogletree

Sweet

Talerico

et al. 2010

The Journal of Heart and Lung Transplantation

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“…However, to the best of our knowledge, we are the first to investigate and demonstrate a direct causal relationship between BNP levels and SERCA expression in the myocardium. This mechanistic connection also may resolve why SERCA upregulation on LVAD support has not always been observed 24 because we found that SERCA mRNA expression recovery was confined to the subgroup of patients that downregulated BNP with the limitation that, because of the availability of tissue from the time of LVAD implantation, we were not able to confirm this recovery also at the protein level. We acknowledge that our clinical data do not prove causality.…”

Section: Discussionmentioning

confidence: 84%

Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca ²⁺ ATPase Expression

et al. 2006

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Background— In heart failure (HF), ventricular myocardium expresses brain natriuretic peptide (BNP). Despite the association of elevated serum levels with poor prognosis, BNP release is considered beneficial because of its antihypertrophic, vasodilating, and diuretic properties. However, there is evidence that BNP-mediated signaling may adversely influence cardiac remodeling, with further impairment of calcium homeostasis. Methods and Results— We studied the effects of BNP on preload-dependent myocardial sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a) expression. In rabbit isolated muscle strips stretched to high preload and shortening isotonically over 6 hours, the SERCA/glyceraldehyde phosphate dehydrogenase mRNA ratio was enhanced by 168% (n=8) compared with unloaded preparations (n=8; P <0.001). Recombinant human BNP at a concentration typically found in end-stage HF patients (350 pg/mL) abolished SERCA upregulation by stretch (n=9; P <0.0001 versus BNP free). Inhibition of cyclic guanosine 3′,5′ monophosphate (cGMP)–phosphodiesterase-5 mimicked this effect, whereas inhibition of cGMP-dependent protein kinase restored preload-dependent SERCA upregulation in the presence of recombinant human BNP. Furthermore, in myocardium from human end-stage HF patients undergoing cardiac transplantation (n=15), BNP expression was inversely correlated with SERCA levels. Moreover, among 23 patients treated with left ventricular assist devices, significant SERCA2a recovery occurred in those downregulating BNP. Conclusions— Our data indicate that preload stimulates SERCA expression. BNP antagonizes this mechanism via guanylyl cyclase-A, cGMP, and cGMP-dependent protein kinase. This novel action of BNP to uncouple preload-dependent SERCA expression may adversely affect contractility in patients with HF.

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“…17 The time constant of the initial decay period was significantly slower in SMMs than in LBMs (248.2Ϯ25.0 ms, nϭ26, Nϭ6 versus 180.1Ϯ17.9 ms, nϭ25, Nϭ6, PϽ0.001; Figure 5F). These …”

Section: ؉ Transients In Smms Have Two Phases and Are Slowly Risingmentioning

confidence: 95%

Adolescent Feline Heart Contains a Population of Small, Proliferative Ventricular Myocytes With Immature Physiological Properties

Chen

Wilson

Kubo

et al. 2007

Circulation Research

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106

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Abstract-Recent studies suggest that rather than being terminally differentiated, the adult heart is a self-renewing organ with the capacity to generate new myocytes from cardiac stem/progenitor cells (CS/PCs). This study examined the hypotheses that new myocytes are generated during adolescent growth, to increase myocyte number, and these newly formed myocytes are initially small, mononucleated, proliferation competent, and have immature properties. Ventricular myocytes (VMs) and cKit ϩ (stem cell receptor) CS/PCs were isolated from 11-and 22-week feline hearts. Bromodeoxyuridine incorporation (in vivo) and p16INK4a immunostaining were measured to assess myocyte cell cycle activity and senescence, respectively. Telomerase activity, contractions, Ca 2ϩ transients, and electrophysiology were compared in small mononucleated (SMMs) and large binucleated (LBMs) myocytes. Heart mass increased by 101% during adolescent growth, but left ventricular myocyte volume only increased by 77%. Most VMs were binucleated (87% versus 12% mononucleated) and larger than mononucleated myocytes. A greater percentage of SMMs was bromodeoxyuridine positive (SMMs versus LBMs: 3.1% versus 0.8%; PϽ0.05), and p16INK4a negative and small myocytes had greater telomerase activity than large myocytes. Contractions and Ca 2ϩ transients were prolonged in SMMs versus LBMs and Ca 2ϩ release was disorganized in SMMs with reduced transient outward current and T-tubule density. The T-type Ca 2ϩ current, usually seen in fetal/neonatal VMs, was found exclusively in SMMs and in myocytes derived from CS/PC. Myocyte number increases during adolescent cardiac growth. These new myocytes are initially small and functionally immature, with patterns of ion channel expression normally found in the fetal/neonatal period (Circ Res. 2007;100:536-544.)

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Altered myocardial Ca2+cycling after left ventricular assist device support in the failing human heart

Cited by 86 publications

References 37 publications

Duration of left ventricular assist device support: Effects on abnormal calcium cycling and functional recovery in the failing human heart

Duration of left ventricular assist device support: Effects on abnormal calcium cycling and functional recovery in the failing human heart

Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca ²⁺ ATPase Expression

Adolescent Feline Heart Contains a Population of Small, Proliferative Ventricular Myocytes With Immature Physiological Properties

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Altered myocardial Ca2+cycling after left ventricular assist device support in the failing human heart

Cited by 86 publications

References 37 publications

Duration of left ventricular assist device support: Effects on abnormal calcium cycling and functional recovery in the failing human heart

Duration of left ventricular assist device support: Effects on abnormal calcium cycling and functional recovery in the failing human heart

Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca 2+ ATPase Expression

Adolescent Feline Heart Contains a Population of Small, Proliferative Ventricular Myocytes With Immature Physiological Properties

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Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca ²⁺ ATPase Expression