ライフサイエンスコーパス: betaARKct

1 betaARKct significantly improved cardiac contractility a

2 Long-term cardiac AAV6-betaARKct gene therapy in HF results in sustained improv

3 selective antagonism of beta(2)ARs abolished betaARKct-mediated cardioprotection, suggesting that enh

4 Ad2/betaARKct significantly reduced neointimal hyperplasia i

5 cacy and safety of an adenoviral vector (Ad2/betaARKct) encoding the carboxyl terminus of beta-adrene

6 uction of the external jugular vein with Ad2/betaARKct (5E9, 5E10, or 5E11 particles per vein) did no

7 In addition, betaARKct alone improves outcomes more than a beta-block

8 Adeno-betaARKct delivery to the failing heart through the LCx

9 oding a peptide inhibitor of betaARK1 (Adeno-betaARKct) or an empty virus (EV) as control.

10 of the carboxyl terminus of betaARK1, Adeno-betaARKct) and tested their ability to potentiate beta-a

11 ization was significantly inhibited in Adeno-betaARKct-infected myocytes (16+/-2%) as compared to Ade

12 V systolic performance was improved in Adeno-betaARKct-treated animals compared with their individual

13 in the LV was significantly higher in Adeno-betaARKct-treated rabbits compared with EV-treated anima

14 In vivo delivery of Adeno-betaARKct is feasible in the infarcted/failing heart by

15 blots demonstrated the presence of the Adeno-betaARKct transgene.

16 LV function in Adv-betaARKct-treated hearts, however, was significantly enh

17 ronary delivery of a betaARK1 inhibitor (Adv-betaARKct) could prevent post-CPB dysfunction.

18 eceive 5x10(11) total viral particles of Adv-betaARKct or PBS.

19 Myocardial gene transfer of Adv-betaARKct stabilizes betaAR signaling and prevents LV dy

20 demonstrate, using cardiac-specific GRK2 and betaARKct-expressing transgenic mice, a deleterious effe

21 uncertain, because GRK2 is still present and betaARKct has other potential effects.

22 Gbetagamma sequestering peptide of betaARK1 (betaARKct) can prevent cardiac dysfunction in models of

23 pression of a peptide inhibitor of betaARK1 (betaARKct) has proven beneficial in several animal model

24 rexpressing a peptide inhibitor of betaARK1 (betaARKct) with transgenic mice overexpressing the sarco

25 delivery of a peptide inhibitor of betaARK1 (betaARKct), that the desensitization and down-regulation

26 nction in the betaARK1(+/-) and betaARK1(+/-)betaARKct mice with the greatest level observed in the b

27 served in the betaARK1(+/-) and betaARK1(+/-)betaARKct myocytes compared with wild-type cells, indica

28 OOH-terminal inhibitor peptide, betaARK1(+/-)betaARKct.

29 greatest level observed in the betaARK1(+/-)betaARKct animals.

30 In contrast, CSQ/betaARKct mice exhibited a significant increase in mean

31 The enhancement of the survival rate in CSQ/betaARKct mice was substantially potentiated by chronic

32 t with the betaAR antagonist metoprolol (CSQ/betaARKct nontreated vs. CSQ/betaARKct metoprolol treate

33 metoprolol (CSQ/betaARKct nontreated vs. CSQ/betaARKct metoprolol treated, 15 +/- 1 weeks vs. 25 +/-

34 tion was significantly improved (CSQ vs. CSQ/betaARKct, left ventricular end diastolic dimension 5.60

35 of metoprolol neither enhanced nor decreased betaARKct-mediated beneficial effects, although metoprol

36 In HF rats, we delivered betaARKct or green fluorescent protein as a control via

37 dministration of adenoviral vectors encoding betaARKct into the jugular vein represents a viable stra

38 or blocked its desensitization by expressing betaARKct, an inhibitor of G protein-coupled receptor ki

39 RK2-derived peptide that binds G(beta)gamma (betaARKct) has benefited some models of heart failure, b

40 severe heart failure, whereas mice with high betaARKct expression showed significantly less cardiac d

41 ated hearts, whereas they were normalized in betaARKct-overexpressing hearts.

42 3% in controls) and significantly smaller in betaARKct mice (16.8+/-1.3%, P<0.05).

43 terminus of beta-adrenergic receptor kinase (betaARKct) in a pig model of arteriovenous PTFE graft fa

44 TG mice with low betaARKct expression developed severe heart failure, whe

45 d the effects of in vivo adenoviral-mediated betaARKct gene transfer on VSM intimal hyperplasia in a

46 In contrast, MLP-/-/betaARKct mice had normal LV chamber size and function.

47 Basal LV contractility in the MLP-/-/betaARKct mice, as measured by LV dP/dtmax, was increase

48 conscious mice, and the level of myocardial betaARKct protein was quantified at termination of the s

49 ng degrees of cardiac-specific expression of betaARKct peptide underwent transverse aortic constricti

50 t by coronary catheterization; expression of betaARKct results in marked reversal of ventricular dysf

51 an effect that was blocked by expression of betaARKct.

52 Importantly, mice with a high level of betaARKct expression had preserved isoproterenol-stimula

53 ive linear relationship between the level of betaARKct protein expression and fractional shortening a

54 rotein betagamma subunits by transfection of betaARKct.

55 The peptide betaARKct, which can inhibit the activation of G protein

56 ession of a Gbetagamma-sequestering peptide, betaARKct (TG betaARKct mice), to test whether the prote

57 a peptide inhibitor of Gbetagamma signaling (betaARKct), we evaluated the role of Gbetagamma in MAP k

58 his study was designed to evaluate long-term betaARKct expression in HF with the use of stable myocar

59 etagamma-sequestering peptide, betaARKct (TG betaARKct mice), to test whether the protection of PC is

60 sphorylation of p70S6K was not blocked in TG betaARKct hearts; therefore, we investigated other targe

61 s toxin treatment and was also blocked in TG betaARKct mice.

62 ase-1 that inhibits Gbetagamma signaling (TG betaARKct mouse).

63 e activated by aortic constriction in the TG betaARKct hearts, suggesting a role for Galpha(q), but n

64 We found that betaARKct, a specific PI3K inhibitor wortmannin, and baf

65 These findings show that betaARKct gene therapy can be of long-term therapeutic v

66 tile function in failing human myocytes, the betaARKct was expressed via adenovirus-mediated (AdbetaA

67 as in animal models of HF, expression of the betaARKct can improve contractile function and beta-adre

68 esults demonstrated that the presence of the betaARKct in injured rat carotid arteries significantly

69 Thus, overexpression of the betaARKct resulted in a marked prolongation in survival

70 seen in human heart failure, delivery of the betaARKct transgene at the time of myocardial infarction

71 knockout mice, as well as expression of the betaARKct, a peptide inhibitor of GRK2 activity.

72 sulted in chamber-specific expression of the betaARKct.

73 peutic potential of GRK2 inhibition with the betaARKct not only in chronic HF but also potentially in

74 ctivation and induction of NO production via betaARKct, and these antiapoptotic/survival effects coul

75 f GRK2 on in vivo myocardial I/R injury with betaARKct imparting cardioprotection.

76 ition was observed in cells transfected with betaARKct but not enriched by sorting.