ライフサイエンスコーパス: PAPP-A

1 PAPP-A >6.0 muIU/ml at presentation was associated with

2 PAPP-A also improved the net reclassification for CVD/MI

3 PAPP-A and its paralog PAPP-A2 are metalloproteases that

4 PAPP-A can cleave IGF binding protein-4 (IGFBP-4), upon

5 PAPP-A is a high molecular weight, zinc-binding metallop

6 PAPP-A is a new candidate marker of unstable angina and

7 PAPP-A is present in unstable plaques, and circulating l

8 PAPP-A levels correlated with levels of C-reactive prote

9 PAPP-A levels were only increased by infliximab (p = 0.0

10 PAPP-A mRNA was expressed by the human fibroblasts and o

11 PAPP-A was abundantly expressed in plaque cells and extr

12 PAPP-A was also associated with higher rates of CVD (HR:

13 PAPP-A was independently associated with recurrent cardi

14 PAPP-A was not related to total or free IGF-1, but posit

15 PAPP-A, PCSK9, and ST2 have been regarded as promising c

16 PAPP-A, proMBP, and C-reactive protein (hs-CRP) serum le

17 ease (P<0.001), aspirin treatment (P<0.001), PAPP-A levels (P<0.001), and PAPP-A/proMBP ratio (P<0.00

18 Our results demonstrate that 1) PAPP-A increases the proliferation and differentiation o

19 governed by its proteolytic activity, and 3) PAPP-A promotes skeletal myogenesis by increasing the am

20 irculating levels of IGF-I, IGF-II, IGFBP-3, PAPP-A, and STC2 were measured by immunoassays.

21 Concentrations of IGFBP-4, PAPP-A, and STC2 on day 0 and 7 were compared to healthy

22 A PAPP-A threshold value of 10 mlU per liter identified pa

23 ls of pregnancy-associated plasma protein A (PAPP-A) in the lowest fifth percentile compared with 17

24 uated pregnancy-associated plasma protein A (PAPP-A), a potentially proatherosclerotic metalloprotein

25 uding Pregnancy-Associated Plasma Protein A (PAPP-A).

26 ysins pregnancy associated plasma protein-A (PAPP-A) and -A2 (PAPP-A2) act as proteinases of insulin-

27 inase pregnancy-associated plasma protein-A (PAPP-A) has been implicated in coronary plaque disruptio

28 Pregnancy-associated plasma protein-A (PAPP-A) is a large metalloproteinase specifically cleavi

29 ether pregnancy-associated plasma protein-A (PAPP-A) is useful for risk assessment in non-ST-segment

30 Pregnancy-associated plasma protein-A (PAPP-A), a member of the metalloproteinase superfamily,

31 Pregnancy-associated plasma protein-A (PAPP-A), a metalloproteinase in the insulin-like growth

32 ng as pregnancy-associated plasma protein-A (PAPP-A), a protein of unknown function found in high con

33 nzyme pregnancy-associated plasma protein-A (PAPP-A), which modulates IGF-I activity.

34 nase, pregnancy-associated plasma protein-A (PAPP-A), which modulates insulin-like growth factor (IGF

35 nase, pregnancy-associated plasma protein-A (PAPP-A).

36 ency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic go

37 Antibodies raised against PAPP-A both inhibited and immunodepleted IGFBP-4 proteas

38 ment (P<0.001), PAPP-A levels (P<0.001), and PAPP-A/proMBP ratio (P<0.001) were correlated with the n

39 atio (3.1+/-1.2 versus 2.7+/-0.8x10(-3)) and PAPP-A levels (5.9+/-1.6 versus 5.1+/-1.4 mIU/L) than th

40 In patients with stable angina, PAPP-A and PAPP-A/proMBP ratio are associated with angiographic pla

41 er, age, severe coronary artery disease, and PAPP-A/proMBP ratio were independent predictors of the n

42 y the human fibroblasts and osteoblasts, and PAPP-A protein was secreted into the culture medium.

43 sought to assess whether PAPP-A, proMBP, and PAPP-A/ProMBP ratio are markers of angiographic plaque c

44 WT/WT and PAPP-A KO mice showed little or no lesion development ev

45 nd were 10-fold higher than in the WT/WT and PAPP-A KO mice.

46 In patients with stable angina, PAPP-A and PAPP-A/proMBP ratio are associated with angio

47 ased assay that STC1 effectively antagonizes PAPP-A-mediated type 1 IGF receptor (IGF1R) phosphorylat

48 (KO), PAPP-A KO, wild-type (WT/WT), and ApoE/PAPP-A double KO (KO/KO) mice.

49 IGFBP-4 fragments generated upon cleavage by PAPP-A were all decreased following treatment with eithe

50 Circulating PAPP-A levels were significantly higher in patients with

51 s-sectionally the association of circulating PAPP-A, PAPP-A2 and STC2 with IGF-1 and its binding prot

52 , hypertension, and coronary artery disease, PAPP-A was independently associated with CVD/myocardial

53 Addition of exogenous PAPP-A also increased the myotube formation and the acti

54 tenoses had a significantly (P<0.001) higher PAPP-A/proMBP ratio (3.1+/-1.2 versus 2.7+/-0.8x10(-3))

55 ly conserved zebrafish homologs of the human PAPP-A gene.

56 ex with a peptide from its substrate IGFBP5 (PAPP-A(BP5)) and also in its substrate-free form, by lev

57 poE KO aortas had 8- to 20-fold increases in PAPP-A, IGFBP-4, and IGF-I mRNA levels compared with non

58 TC2, STC2(C120A), which is unable to inhibit PAPP-A, grow like wild-type mice.

59 ntly, we show that STC2 efficiently inhibits PAPP-A-mediated IGF receptor signaling in vitro and that

60 STC1 potently (Ki = 68 pm) inhibits PAPP-A cleavage of IGFBP-4, and we show in a cell-based

61 been found that the homologous STC2 inhibits PAPP-A proteolytic activity, and that this depends on th

62 icient mice, generating ApoE knock-out (KO), PAPP-A KO, wild-type (WT/WT), and ApoE/PAPP-A double KO

63 Transient overexpression of the full-length PAPP-A-(1-1547), but not truncated protease-inactive N-t

64 We measured PAPP-A at baseline in 3,782 patients with non NSTE-ACS r

65 Moreover, PAPP-A purified from pregnancy sera had IGF-dependent IG

66 uctures of the catalytically inactive mutant PAPP-A (E483A) in complex with a peptide from its substr

67 he regulation of IGF and IGFBP-4, as neither PAPP-A nor STC2 were discernibly affected.

68 The associations of PAPP-A, PAPP-A2 and STC2 with IGF-1 or IGFBPs were inves

69 n of myoblasts, 2) the stimulatory effect of PAPP-A on myogenesis is governed by its proteolytic acti

70 We examined the level of expression of PAPP-A in eight culprit unstable coronary plaques and fo

71 t evidence for a non-proteolytic function of PAPP-A.

72 llele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resul

73 o relationship between having a low level of PAPP-A and maternal age, ethnicity, parity, height, body

74 nalyzed by cause of stillbirth, low level of PAPP-A was strongly associated with stillbirth due to pl

75 We also measured circulating levels of PAPP-A, C-reactive protein, and insulin-like growth fact

76 biochemical studies reveal the mechanism of PAPP-A substrate binding and selectivity.

77 Overexpression of PAPP-A led to degradation of the IGFBP-2 produced by C2C

78 However, the role of PAPP-A and its mechanism of action in various cellular p

79 this study, we have investigated the role of PAPP-A in skeletal myogenesis using C2C12 myoblasts.

80 P-A-IGFBP5 interaction is not found in other PAPP-A substrates.

81 tioned medium of HT1080 cells overexpressing PAPP-A.

82 Plasma PAPP-A, PAPP-A2, total and free IGF-1, IGFBP-1, IGFBP-2,

83 Binding of STC2 prevents PAPP-A cleavage of insulin-like growth factor-binding pr

84 Recombinant PAPP-A was purified from the conditioned medium of HT108

85 AMA was associated with lower maternal serum PAPP-A and sFlt and a higher PlGF:sFlt ratio.

86 P5 anchor peptide that mediates the specific PAPP-A-IGFBP5 interaction is not found in other PAPP-A s

87 ith clinical indicators plus BNP, cTnI, ST2, PAPP-A, and MPO (each p</=0.01) [corrected].

88 b exert different effects on levels of STC2, PAPP-A, and IGFBP-4, thereby explaining the distinct met

89 This finding supports PAPP-A as a candidate prognostic marker in patients with

90 tive N-terminal PAPP-A-(1-920) or C-terminal PAPP-A-(1100-1547), significantly enhanced the prolifera

91 t not truncated protease-inactive N-terminal PAPP-A-(1-920) or C-terminal PAPP-A-(1100-1547), signifi

92 We further demonstrate that PAPP-A trans-dimer formation and distal inter-domain int

93 ro and in situ experiments demonstrated that PAPP-A cleaves insulin-like growth factor-binding protei

94 These data indicate that PAPP-A plays a critical role in lesion development in a

95 We show that PAPP-A is a flexible trans-dimer that binds IGFBP5 via a

96 e-resistant IGFBP-4 completely abolished the PAPP-A-induced proliferation of C2C12 myoblasts.

97 ally, we illustrate the critical role of the PAPP-A central domain as it mediates both IGFBP5 recogni

98 It rather binds to PAPP-A with high affinity (KD = 75 pm).

99 nd that STC1 is unable to bind covalently to PAPP-A, in agreement with the absence of a corresponding

100 and at the same time assigned a function to PAPP-A.

101 ibition requires covalent binding of STC2 to PAPP-A and is mediated by a disulfide bond, which involv

102 We sought to assess whether PAPP-A, proMBP, and PAPP-A/ProMBP ratio are markers of a

103 To determine whether PAPP-A plays an active role in the development of athero

104 ed mice lacking apolipoprotein E (ApoE) with PAPP-A-deficient mice, generating ApoE knock-out (KO), P

105 as no difference in the risk associated with PAPP-A stratified by baseline cardiac troponin I [Accu-T

106 Treatment of C2C12 myoblasts with PAPP-A increased their proliferation in a dose- and time