ライフサイエンスコーパス: failing heart

1 SCs) is an emerging therapy for treating the failing heart.

2 cal therapies as a bridge to recovery of the failing heart.

3 e diastolic stiffness of the healthy and the failing heart.

4 erfusion by enhancing neoangiogenesis in the failing heart.

5 red SSB is observed in cardiomyocytes of the failing heart.

6 lation of INa by biventricular pacing of the failing heart.

7 ling and preserve cardiac performance in the failing heart.

8 get or affect the ANS and its effects on the failing heart.

9 es maladaptation of energy substrates in the failing heart.

10 significantly increases the function of the failing heart.

11 duce arrhythmogenic cardiac alternans in the failing heart.

12 olites, and metabolic flux in the normal and failing heart.

13 of caPI3K vector can improve function of the failing heart.

14 dent of exercise can restore function of the failing heart.

15 athological mechanism for this kinase in the failing heart.

16 tive stress increases PDE5 expression in the failing heart.

17 OGT (cmOGT KO) and ascertain its role in the failing heart.

18 tween metabolism and cardiac function in the failing heart.

19 ic conditions associated with the normal and failing heart.

20 lication and depletion of mtDNA in the human failing heart.

21 dependent pathology in the hypertrophied and failing heart.

22 Mg29 to model this observed induction in the failing heart.

23 ume occurred with increased afterload in the failing heart.

24 athy and severe CHF improves function of the failing heart.

25 d hormone (T3) that develops in the advanced failing heart.

26 contribute to their beneficial effect on the failing heart.

27 by reactive oxygen species generated in the failing heart.

28 ent, would increase function of the actively failing heart.

29 lyl cyclase VI increases the function of the failing heart.

30 rate metabolism and function in the advanced failing heart.

31 s adenosine may act to inhibit MVO(2) in the failing heart.

32 i) signalling in the normal and mechanically failing heart.

33 nical implications for the management of the failing heart.

34 e myocardial performance in the ischemic and failing heart.

35 tion should improve the contractility of the failing heart.

36 th diminished cardiomyocyte apoptosis in the failing heart.

37 ributor to the impaired contractility of the failing heart.

38 tative/inotropic action that may benefit the failing heart.

39 abolism and describe how this changes in the failing heart.

40 isms regulating homeostasis of NAD(+) in the failing heart.

41 ping new Ca(2+) buffering strategies for the failing heart.

42 downregulated in myocardial samples from the failing heart.

43 D maps show areas of conduction block in the failing heart.

44 ratures are appropriate for the resuscitated failing heart.

45 TPase (SERCA2a) activity is deficient in the failing heart.

46 ng initiated wave reentry and breakup in the failing heart.

47 gnaling within cardiomyocytes develop in the failing heart.

48 he dysfunctional substrate metabolism of the failing heart.

49 nans is significantly more pronounced in the failing heart.

50 NAD(+) ratio) and protein acetylation in the failing heart.

51 stabilizing myocardial NAD(+) levels in the failing heart.

52 latory system occur in the hypertrophied and failing heart.

53 refore, PKG1alpha activation can benefit the failing heart.

54 inding protein, is up-regulated in the human failing heart.

55 buting to focal arrhythmia in the intact non-failing heart.

56 a, thereby suppressing FA utilization in the failing heart.

57 e predominant GRK isoform upregulated in the failing heart.

58 FA metabolism and cardiac dysfunction in the failing heart.

59 e A signaling seems to be beneficial for the failing heart.

60 related signaling pathways characterize the failing heart.

61 lopment of novel metabolic therapies for the failing heart.

62 also observed in biopsies derived from human failing hearts.

63 channel trafficking that is downregulated in failing hearts.

64 t altered in left ventricular hypertrophy or failing hearts.

65 egulation of heme and non-heme iron in human failing hearts.

66 ignificantly less (P=0.011) by almost 80% in failing hearts.

67 phorylated, resulting in "leaky" channels in failing hearts.

68 equally effective in myocytes from normal or failing hearts.

69 evels are maintained above baseline in human failing hearts.

70 phate (cGMP) signaling is characteristic for failing hearts.

71 similar in LV and BiV pacing, especially in failing hearts.

72 fraction from 42+/-12 to 3+/-2 (P=0.005) in failing hearts.

73 d by comparing B-treated with drug-untreated failing hearts.

74 activation improves contractile function in failing hearts.

75 also found reduced SIRT6 expression in human failing hearts.

76 cytes contributed to the upregulation in the failing hearts.

77 ications of this finding are investigated in failing hearts.

78 vation might improve contractile function in failing hearts.

79 ed a moderate increase in RV trabeculae from failing hearts.

80 aracteristics resembling those isolated from failing hearts.

81 mponent slow rise at the subendocardium in 3 failing hearts.

82 han the subepicardium in both nonfailing and failing hearts.

83 on of SERCA2a itself were greatly reduced in failing hearts.

84 stream gene expression were unchanged in the failing hearts.

85 s PGC-1alpha protein increased by 58% in the failing hearts.

86 quitin proteasome system activity in HCM and failing hearts.

87 associated with the loss of positive FFR in failing hearts.

88 oxidative damage was increased by 50% in the failing hearts.

89 rocess of mtDNA, was decreased by 75% in the failing hearts.

90 or of cardiac hypertrophy, is inactivated in failing hearts.

91 in expression implicated in human and animal failing hearts.

92 ion and size were similar in both normal and failing hearts.

93 ression is downregulated in human and animal failing hearts.

94 nges have been described in hypertrophic and failing hearts.

95 R2 is required for the beneficial effects in failing hearts.

96 -labeling (TUNEL) in myocardial samples from failing hearts.

97 deltac-dependent arrhythmogenic disorders in failing hearts.

98 ubiquitinated proteins are observed in human failing hearts.

99 tion of Ca cycling by protecting stressed or failing hearts.

100 erformance and reduced functional reserve in failing hearts.

101 appears to be significantly downregulated in failing hearts.

102 rs of the LV, but was unchanged in the RV of failing hearts.

103 lated from canine tachycardic pacing-induced failing hearts.

104 l JMC protein SPEG is downregulated in human failing hearts.

105 uclear-1 were substantially downregulated in failing hearts.

106 or lipoxygenases attenuated mPTP opening in failing hearts.

107 umol/L peroxide exposure and in myocyte from failing hearts.

108 ts an additional layer of gene regulation in failing hearts.

109 of normalizing NADH/NAD(+) imbalance in the failing hearts.

110 pic slices isolated from donor and end-stage failing hearts.

111 been shown to provide functional support to failing hearts.

112 icular wedge preparations of human donor and failing hearts.

113 of JMCs underlies contractile dysfunction in failing hearts.

114 shortened action potential duration only in failing hearts.

115 tor and inotropic response were decreased in failing hearts.

116 rts 2 to 78 years of age and in 17 explanted failing hearts 22 to 70 years of age.

117 In failing hearts, 30S proteasomes were significantly lower

118 A (PDE3A) was significantly reduced in human failing hearts, accompanied by up-regulation of inducibl

119 ectrically stimulated myocytes from ischemic failing hearts, AdMYH6 increased the contractile amplitu

120 ement of left ventricular dysfunction in the failing heart after myocardial infarction or doxorubicin

121 ence in regional work between nonfailing and failing hearts after MI and offer novel insight into the

122 P2 in cardiomyocytes facilitated recovery of failing hearts after reversible transverse aortic constr

123 (mtDNA) content was decreased by >40% in the failing hearts, after normalization for a moderate decre

124 onverting enzyme (ACE) is upregulated in the failing heart and has been associated with disease progr

125 een insights into the pathophysiology of the failing heart and illuminate a previously unrecognized p

126 of NAD(+) biosynthetic enzymes in the human failing heart and in the heart of a mouse model of dilat

127 n HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and

128 e immune-mediated injurious responses in the failing heart and retain this memory on adoptive transfe

129 GRK2 and GRK5 are overexpressed in the failing heart and thus have become therapeutic targets.

130 oxidative and/or nitrosative stresses in the failing heart and vascular tree, which contribute to the

131 protein or FKBP12.6) causes SR Ca2+ leak in failing hearts and can trigger fatal ventricular arrhyth

132 In both failing hearts and cultured cardiac myocytes, the increa

133 d the increased abundance of c-kit+ cells in failing hearts and demonstrated frequent coexpression of

134 PDE2 is markedly up-regulated in failing hearts and desensitizes against acute beta-AR st

135 and succinate decreased from non-failing to failing hearts and did not change significantly post-LVA

136 ic amino acids decreased from non-failing to failing hearts and did not change significantly post-LVA

137 te values both decreased from non-failing to failing hearts and increased again significantly in the

138 cause mitochondrial function is depressed in failing hearts and iron accumulation can lead to oxidati

139 PDE5 is upregulated in hypertrophied and failing hearts and is thought to contribute to their pat

140 e myocyte contribution to their induction in failing hearts and the underlying regulatory mechanism i

141 ion was decreased in end-stage human DCM and failing hearts and, most importantly, a significant incr

142 ll O-GlcNAc in donor, 68 +/- 9% in end-stage failing heart, and 76 +/- 6% in myectomy muscle samples

143 ged AP duration exclusively in myocytes from failing heart, and the critical conductance required for

144 utophagy may be an adaptive mechanism in the failing heart, and this phenomenon is attenuated by LVAD

145 rdial effects of dyssynchrony and CRT in the failing heart, and we highlight new research aiming to b

146 transcript abundance between nonfailing and failing hearts, and between failing an LVAD-supported he

147 e cardiac metabolites in non-failing hearts, failing hearts, and hearts post-LVAD support.

148 n is up-regulated in human hypertrophied and failing hearts, and its inhibition (e.g., by sildenafil)

149 in human nonfailing donor hearts, explanted failing hearts, and myectomy samples from patients with

150 n expression was down-regulated in end-stage failing hearts, and that this effect was reverted upon m

151 dyssynchrony is induced by RBBB than LBBB in failing hearts, and the corresponding impact of CRT on t

152 Th1) and Th17 (versus Treg) predominance in failing hearts, and with expansion of memory T cells in

153 In failing heart, AP morphology was dramatically altered, w

154 er abnormal calcium-handling proteins in the failing heart are candidates for gene therapy; many shor

155 rial dysfunction and energy depletion in the failing heart are innovative therapeutic targets in hear

156 hondrial function, also are present in human failing hearts as well as in mouse hearts with pathologi

157 activity were significantly reduced in human failing hearts as well as mouse hearts with chronic pres

158 Finally, in failing heart, asymmetry of transmural electrical propag

159 2 cm/s (95% CI, 27-37; P=0.001) in 12 native failing hearts at 1000 ms pacing cycle length (PCL).

160 First described in failing hearts, autophagy within the cardiovascular syst

161 First described in failing hearts, autophagy within the cardiovascular syst

162 stress but is ultimately detrimental in the failing heart because of accrual of cardiomyocyte death.

163 orms might have therapeutic potential in the failing heart because they increase the maximal force of

164 ransients duration (CaD) in donor but not in failing hearts, because of desensitization of beta1-adre

165 This shift was also observed in human failing heart biopsies in comparison with nonfailing con

166 ally nonuniform alteration of AP duration in failing heart blunted the transmural gradient of repolar

167 reased conduction velocity in both donor and failing hearts but shortened action potential duration o

168 e altered Ca(2+) regulatory phenotype of the failing heart, but PKA-mediated phosphorylation of RyRS2

169 bioenergetics is a prominent feature of the failing heart, but the underlying metabolic perturbation

170 ated to glucose metabolism are diminished in failing hearts, but recovered their values post-LVAD.

171 In failing hearts, Ca2+ cycling is profoundly altered, resu

172 stable increased expression of S100A1 in the failing heart can be used for long-term reversal of LV d

173 The findings indicate that in the failing heart cell, NCX inhibition can improve SR Ca2+ l

174 ied to probe TATS electrical conductivity in failing heart cells.

175 sed to increase cardiac contractility of the failing heart center on increasing the amount of calcium

176 This pattern of remodeling was attenuated in failing hearts chronically unloaded with a left ventricu

177 In human failing heart, CM Tln1 also increases compared with cont

178 nsient duration was significantly smaller in failing hearts compared with nonfailing hearts at fast p

179 Global S-nitrosylation was decreased in failing hearts compared with nonfailing.

180 ts were significantly increased in SOCS3 cKO failing hearts compared with wild-type hearts.

181 derstand why MyBP-C dephosphorylation in the failing heart contributes to contractile dysfunction and

182 Failing hearts demonstrated depressed LV ejection fracti

183 cycle length decreases, both the normal and failing heart develop T-wave alternans, but only the fai

184 se 4 (HDAC4), upregulation of ANP and BNP in failing hearts did not require increased histone acetyla

185 A failing heart differs from healthy hearts by an array of

186 entricular myocytes isolated from normal and failing hearts displayed no inotropic response to CGRP,

187 The failing heart displays increased glycolytic flux that is

188 In human failing hearts, Drp1 phosphorylation at S616 is increase

189 ces (LVADs) induce reverse remodeling of the failing heart except for the extracellular matrix, which

190 been observed experimentally that cells from failing hearts exhibit elevated levels of reactive oxyge

191 was prepared from 7 human nonfailing and 10 failing heart explants.

192 In animal and human failing hearts, expression of JP2 is decreased markedly,

193 ar wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for trans

194 et out to measure cardiac metabolites in non-failing hearts, failing hearts, and hearts post-LVAD sup

195 mitochondrial membrane are reviewed for the failing heart from the perspectives of chronic pressure

196 abetic patients but not in normal hearts and failing hearts from lean, nondiabetic humans.

197 ge amylin oligomers, fibrils, and plaques in failing hearts from obese and diabetic patients but not

198 t studies also identified amylin deposits in failing hearts from patients with obesity or type 2 diab

199 Failing hearts further demonstrated spatially discordant

200 In failing hearts, G6PD is upregulated and generates reduce

201 Third, calcium transient in failing hearts had a flattened plateau at the midmyocard

202 Failing hearts had exaggerated electrophysiological resp

203 Surprisingly, SOCS3 cKO failing hearts had minimal histological abnormalities wi

204 ocaine autoradiography to determine that the failing heart has 30% lower SCN5A levels - the first ev

205 Our findings indicate that the failing heart has a previously unrecognized reparative c

206 Since the failing heart has increased reliance on glucose, the inf

207 lar complexes isolated from murine and human failing hearts have reduced CaMKIIdelta levels.

208 During AF in failing hearts, heterogeneous spatial distribution of fi

209 amage and DDR activation are observed in the failing heart, however, the type of DNA damage and its r

210 in vivo gene transfer of AAV9.SERCA2a in the failing heart improved left ventricular contractile func

211 s to provide hemodynamic augmentation in the failing heart in most patients.

212 ar in femoral vascular rings from normal and failing hearts in dogs.

213 n increases dramatically in hypertrophic and failing hearts in rodent models and in humans.

214 in vitro and upregulated ACE2 expression in failing hearts in vivo.

215 ves contraction and relaxation in normal and failing hearts in vivo.

216 t of metabolomic changes in hypertrophic and failing hearts in vivo.

217 e several components of the phenotype of the failing heart, including contractile function, interstit

218 The overexpression of cTnI-ND in Gsalpha-DF failing hearts increased relaxation velocity and left ve

219 nnels arachidonic acid into EETs, whereas in failing hearts, increased iPLA2gamma activity channels A

220 bservations provide direct evidence that the failing heart is "energy starved" as it relates to CK.

221 stolic function, the question of whether the failing heart is "energy starved" has been debated for d

222 Thus, induction of Mg29 in the failing heart is a compensatory response that directly c

223 HO-1 induction in the failing heart is an important cardioprotective adaptatio

224 The deficit in ATP supplied by CK in the failing heart is cardiac-specific and potentially of suf

225 Significant evidence indicates that the failing heart is energy starved.

226 The failing heart is hypothesized to suffer from energy supp

227 The failing heart is subject to elevated metabolic demands,

228 nce of GRK5 up-regulation in the injured and failing heart is the induction of NF-kappaB expression a

229 hallmark of cells and tissues isolated from failing hearts is prolongation of action potential durat

230 actile performance in human and experimental failing hearts, is impaired calcium sequestration into t

231 In the failing heart, it has long been established that multipl

232 To develop therapies aimed at rescuing the failing heart, it is important to understand the molecul

233 of myocardial creatine are a hallmark of the failing heart, leading to the widely held view that crea

234 eptor-alpha (PPARalpha) in hypertrophied and failing hearts leads to the reappearance of the fetal me

235 turnover is reduced in pressure-overloaded, failing hearts, limiting the availability of this rich s

236 (GRKs), some of which are upregulated in the failing heart, making them desirable therapeutic targets

237 results suggest that IF1 upregulation in the failing heart may be a maladaptive response.

238 that the downregulation of PDE3A observed in failing hearts may play a causative role in the progress

239 rotein were decreased significantly in human failing hearts (n=10) compared with normal hearts (n=3;

240 Remodeled TTs in cells from failing hearts no longer exist in the regularly organize

241 data show that SERCA2a gene transfer in the failing heart not only improves contractile function but

242 implant) and 8 post-LVAD hearts, plus 8 non-failing hearts obtained from the tissue bank at the Univ

243 a 30% loss in levels of NAD(+) in the murine failing heart of both DCM and transverse aorta constrict

244 Our findings indicate that the failing heart of patients with type 2 diabetes mellitus

245 ological injury in mice and was increased in failing hearts of both mice and humans.

246 s, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly

247 proach could enhance contractile function in failing hearts of various etiologies, even here where re

248 444 mRNAs that were altered by >1.3-fold in failing hearts, only 29 mRNAs normalized by as much as 2

249 In the failing heart, oxidative stress occurs in the myocardium

250 ially restored after mechanical unloading in failing hearts (P<0.01) and was significantly lower in H

251 In the failing heart, persistent beta-adrenergic receptor activ

252 In failing heart, preferential conduction from subendocardi

253 ial nNOS expression and activity increase in failing hearts, raising the possibility that nNOS may in

254 ing in cardiomyocytes from hypertrophied and failing hearts, reflected as increased diastolic Ca(2+)

255 ncomitant reduction of Sir2alpha activity in failing hearts regulate the post-translational acetylati

256 Similarly, MeCP2 repression in human failing hearts resolved after unloading by a left ventri

257 d and phospholamban is hypophosphorylated in failing hearts, resulting in impaired SR Ca2+ reuptake t

258 Human end-stage failing hearts revealed higher CaMKII expression/activit

259 the cell and tissue level have increased the failing heart's susceptibility to dynamic instabilities

260 results indicate that the hypertrophied and failing heart shifts to ketone bodies as a significant f

261 trometry revealed that the hypertrophied and failing heart shifts to oxidizing ketone bodies as a fue

262 heart develop T-wave alternans, but only the failing heart shows QRS alternans (although moderate) at

263 In myocytes from failing hearts, stimulation of PKA failed to induce a sh

264 to exert profound beneficial effects in the failing heart, suggesting a significant role for PDE5 in

265 expression are present in the myocardium of failing hearts, suggesting a potential role for iNOS in

266 repair and antioxidant genes were reduced in failing hearts, suggestive of a defective repair and pro

267 he pattern of metabolite derangements in the failing heart suggests bottlenecks of carbon substrate f

268 ular [Ca(2+)] and [cAMP], which are lower in failing hearts than in normal hearts.

269 oform might offer functional advantages in a failing heart that is expressing only the beta-MHC isofo

270 c remodeling common to both hypertrophic and failing hearts that are indicative of extracellular matr

271 g function of the postinfarction chronically failing heart, there was late-phase arrhythmogenicity sp

272 miRNA changes in failing heart tissues partially resembled that of fetal

273 n targeting mitochondrial dysfunction in the failing heart to revive the myocardium and its contracti

274 In the failing hearts, transmural activation was significantly

275 n geometric remodeling in the dyssynchronous failing heart versus control.

276 reased betaARK1-coupled PI3K activity in the failing hearts was associated with downregulation of bet

277 achidonic acid (AA) in mitochondria from non-failing hearts was calcium-dependent phospholipase A2zet

278 ble alterations of NAD(+) homeostasis in the failing heart, we quantified the expression of NAD(+) bi

279 junctin levels are severely reduced in human failing hearts, we performed an in-depth study of the me

280 METHODS AND Leukocytes infiltrating the failing heart were analyzed by a multistep enzymatic pro

281 solated ventricular myocytes from normal and failing hearts were not different (P=0.8, not significan

282 f several pathologies including ischemic and failing heart where they demonstrated efficacy.

283 Ca(2+) cycling perturbations manifest in the failing heart, where their protein levels are significan

284 ase termination was changed in myocytes from failing hearts, where remodelling processes lead to alte

285 The need for mechanical assistance of the failing heart, whether acute after a myocardial infarcti

286 ently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive

287 ft ventricular hypertrophy, but decreased in failing hearts, while ryanodine receptor was unchanged i

288 yofiber mechanics during LVP and BiVP in the failing heart with left bundle branch block.

289 egies for normalizing gene expression in the failing heart with small molecules that control signal t

290 f cardiac resynchronization therapy (CRT) in failing hearts with a pure right (RBBB) versus left bund

291 ure [dP/dt(max)]) was similarly depressed in failing hearts with both conduction delays.

292 ronization therapy is effective for treating failing hearts with conduction delay and discoordinate c

293 a-actin isoforms in human healthy hearts and failing hearts with dilated cardiomyopathy (DCM).

294 ignificantly changed in the hypertrophied or failing heart, with the notable exception of a progressi

295 ver the roles of cardiac titin in normal and failing hearts, with a special emphasis on the contribut

296 idates are often differentially expressed in failing hearts, with an inverse correlation between 3'UT

297 ved a significant increase in heme levels in failing hearts, with corresponding feedback inhibition o

298 ea of LV lateral wall in both nonfailing and failing hearts, with modest anterior or posterior deviat

299 Cardiac dyssynchrony in the failing heart worsens global function and efficiency and

300 process of deterioration from a healthy to a failing heart yet remains deficiently understood.