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JournalISSN: 0022-2828

Journal of Molecular and Cellular Cardiology

About: Journal of Molecular and Cellular Cardiology is an academic journal. The journal publishes majorly in the area(s): Ischemia & Myocyte. It has an ISSN identifier of 0022-2828. Over the lifetime, 11345 publication(s) have been published receiving 389392 citation(s). more

Topics: Ischemia, Myocyte, Heart failure more

Open accessJournal ArticleDOI: 10.1016/J.YJMCC.2012.03.006
Abstract: The utility of anthracycline antineoplastic agents in the clinic is compromised by the risk of cardiotoxicity. It has been calculated that approximately 10% of patients treated with doxorubicin or its derivatives will develop cardiac complications up to 10 years after the cessation of chemotherapy. Oxidative stress has been established as the primary cause of cardiotoxicity. However, interventions reducing oxidative stress have not been successful at reducing the incidence of cardiotoxicity in patients treated with doxorubicin. New insights into the cardiomyocyte response to oxidative stress demonstrate that underlying differences between in vitro and in vivo toxicities may modulate the response to superoxide radicals and related compounds. This has led to potentially new uses for pre-existing drugs and new avenues of exploration to find better pharmacotherapies and interventions for the prevention of cardiotoxicity. However, much work still must be done to validate the clinical utility of these new approaches and proposed mechanisms. In this review, the authors have reviewed the molecular mechanisms of the pathogenesis of acute and chronic doxorubicin-induced cardiotoxicity and propose potential pharmacological interventions and treatment options to prevent or reverse this specific type of heart failure. more

Topics: Cardiotoxicity (65%), Anthracycline (54%)

893 Citations

Journal ArticleDOI: 10.1006/JMCC.2001.1367
Ming Zhang1, Danielle Methot1, Veronica Poppa1, Yasushi Fujio1  +2 moreInstitutions (1)
Abstract: M. Zhang, D. Methot, V. Poppa, Y. Fujio, K. Walsh and C. E. Murry. Cardiomyocyte Grafting for Cardiac Repair: Graft Cell Death and Anti-Death Strategies. Journal of Molecular and Cellular Cardiology (2001) 33, 907–921. Recent studies indicate that cardiomyocyte grafting forms new myocardium in injured hearts. It is unknown, however, whether physiologically significant amounts of new myocardium can be generated. Pilot experiments showed that death of grafted rat neonatal cardiomyocytes limited formation of new myocardium after acute cryoinjury. Time-course studies showed that, at 30 min after grafting, only 1.8(±0.4)% of graft cells were TUNEL-positive. At 1 day, however, TUNEL indices increased to 32.1(±3.5)% and remained high at 4 days, averaging 9.8(±3.8)%. By 7 days, TUNEL decreased to 1.0(±0.2)%. Electron microscopy revealed that dead cells had features of both irreversible ischemic injury and apoptosis. To test whether ischemia contributed to poor graft survival, grafts were placed into vascularized 2-week-old cardiac granulation tissue or normal myocardium. TUNEL indices were reduced by 53% and 86%, respectively. Adenoviral infection of graft cells with the cytoprotective kinase Akt, or constitutively active Akt, reduced TUNEL indices by 31% and 40%, respectively, compared to β -gal-transfected controls. Neither treatment reached statistical significance compared to untreated controls, however. Heat shock reduced cardiomyocyte death in vitro in response to serum deprivation, glucose depletion, and viral activation of the Fas death pathway. When cardiomyocytes were heat shocked prior to grafting, graft cell death in vivo was reduced by 54% at day 1. Therefore, high levels of cardiomyocyte death occur for at least 4 days after grafting into injured hearts, in large part due to ischemia. Death can be limited by activating the Akt pathway and even more effectively by heat shock prior to transplantation. more

Topics: Cellular cardiomyoplasty (54%), Necrosis (52%), Transplantation (51%) more

846 Citations

Journal ArticleDOI: 10.1016/0022-2828(92)90114-F
Abstract: The hypothesis of a Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) is supported by experiments done in skinned cardiac cells (sarcolemma removed by microdissection). According to this hypothesis, the transsarcolemmal Ca2+ influx does not activate the myofilaments directly but through the induction of a Ca2+ release from the SR. The stimulus gating CICR is not a small change in free Ca2+ concentration (delta[free Ca2+]) outside the SR but a function of the rate of this change (delta[free Ca2+/delta t]). The initial relatively fast component of the transsarcolemmal Ca2+ current would trigger Ca2+ release; the subsequent slow component, perhaps corresponding to noninactivating Ca2+ channels, would load the SR with an amount of Ca2+ available for release during subsequent beats. Inactivation of CICR is caused by the large increase of [free Ca2+] outside the SR resulting from Ca2+ release, which inhibits further release. This negative feedback helps to explain that CICR is not all or none. During relaxation the Ca2+ reaccumulation in the SR is backed up by the Ca2+ efflux across the sarcolemma through Na+-Ca2+ exchange and the sarcolemmal Ca2+ pump. Computations of the Ca2+ buffering in the mammalian ventricular cell and of the systolic transsarcolemmal Ca2+ influx do not support the alternative hypothesis that this influx of Ca2+ is large enough to activate the myofilaments directly. Yet the hypothesis of a CICR can be challenged because of many problems and uncertainties related to the preparations and methods used for skinned cardiac cell experiments. more

Topics: Ryanodine receptor 2 (52%)

757 Citations

Journal ArticleDOI: 10.1016/0022-2828(78)90401-7
Abstract: Electrophoretic analysis in pyrophosphate gels of intact myosin of adult rat myocardium revealed the presence of five distinct components, two in atrial myosin (A1, A2) and three in ventricular myosin (V1, V2, V3). Analysis of Ca2+-activated myosin ATPase activity in the gels revealed that A1, A2 and V1 had about the same specific activity; V3 had the lowest activity, while that of V2 was intermediate. At 3 weeks of age, ventricular myosin was exclusively V1, there being a slow age-dependent shift in myosin distribution toward the adult pattern. Hypophysectomy of juvenile rats caused a shift towards V3, which by 45 days after operation accounted for 90% of total myosin. This shift was prevented by daily administration of 5 μg of thyroxine. When chronically hypophysectomized rats were similarly treated, there was a rapid shift of myosin components towards V1. These changes in distribution of myosin components were associated with appropriate changes in Ca2+-activated ATPase activity of electrophoretically purified ventricular myosin as measured in the gel. Sodium dodecyl sulphate gel analysis of purified myosin showed little or no contaminants. For both V1 and V3 rich myosins, the ratio of the two ventricular light chains (V-LC1, V-LC2) and the ratio of light chains to heavy chains are consistent with the model that each intact molecule contains two each of V-LC1 and V-LC2. Sodium dodecyl sulphate electrophoresis of purified atrial myosin revealed two types of light chains: A-LC1 (mol. wt 27 000, not resolved from V-LC1) and A-LC2 (mol. wt 22 000), the latter being distinct from V-LC2. more

Topics: Myosin light-chain kinase (74%), Myosin (62%), Ventricular Myosins (53%) more

756 Citations

Journal ArticleDOI: 10.1016/J.YJMCC.2005.07.003
Abstract: Circulating endothelial progenitor cells (EPC) are incorporated into newly formed capillaries, enhance neovascularization after hind limb ischemia and improve cardiac function after ischemic injury. Incorporated progenitor cells may also promote neovascularization and cardiac regeneration by releasing factors, which act in a paracrine manner to support local angiogenesis and mobilize tissue residing progenitor cells. Therefore, we analyzed the expression profile of cytokines in human peripheral blood-derived EPC as opposed to human umbilical vein endothelial cells (HUVEC), human microvascular endothelial cells (HMVEC), and CD14+ monocytes by microarray technology. A gene tree analysis revealed a distinct expression pattern of angiogenic growth factors in EPC, mature endothelial cells, and CD14+ monocytes. VEGF-A, VEGF-B, SDF-1, and IGF-1 mRNA levels were higher in EPC as compared to HUVEC or HMVEC. The enhanced mRNA expression was paralleled by a significant release of VEGF, SDF-1, and IGF-1 protein into the cell culture supernatant of EPC. Moreover, immunohistological analysis of ischemic limbs from nude rats revealed that VEGF is also released from recruited human EPC in vivo. As a functional consequence, conditioned medium of EPC induced a strong migratory response of mature endothelial cells, which was significantly inhibited by VEGF and SDF-1 neutralizing antibodies. Finally, conditioned medium of EPC significantly stimulated the migration of cardiac resident c-kit+ progenitor cells in vitro. Taken together, EPC exhibit a high expression of angiogenic growth factors, which enhanced migration of mature endothelial cells and tissue resident cardiac progenitor cells. In addition to the physical contribution of EPC to newly formed vessels, the enhanced expression of cytokines may be a supportive mechanism to improve blood vessel formation and cardiac regeneration after cell therapy. more

Topics: Endothelial stem cell (63%), Vasculogenesis (63%), Angiogenesis (61%) more

741 Citations

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Journal's top 5 most impactful authors

David J. Hearse

64 papers, 3.3K citations

Lionel H. Opie

49 papers, 1.3K citations

Derek M. Yellon

48 papers, 2.8K citations

Donald M. Bers

45 papers, 2.8K citations

Roberto Ferrari

44 papers, 1.4K citations

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