ライフサイエンスコーパス: IPAH

1 IPAH may be associated with pulmonary endothelial dysfun

2 IPAH pulmonary artery endothelial cells had decreased mi

3 Seventeen of 26 IPAH patients performed the total PET study.

4 blood samples of 237 normal subjects and 268 IPAH patients.

5 P=0.017) in a matched-pair analysis of n=336 IPAH patients.

6 nsion with interstitial lung disease, and 67 IPAH).

7 an international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH).

8 Although IPAH/pulmonary artery endothelial cells' ATP content was

9 alleled reduction in Complex IV activity and IPAH cellular NO synthesis.

10 N-acetylglucosamine hydrolase in control and IPAH cells and tissues.

11 is available and may be offered to HPAH and IPAH patients but should be preceded by genetic counseli

12 Gene functional groups shared by SSc-PAH and IPAH lungs included those involved in antigen presentati

13 es in treatment response between CTD-PAH and IPAH.

14 RV afterload was similar in SScPAH and IPAH (pulmonary vascular resistance=7.0+/-4.5 versus 7.9

15 C6 small interfering RNA markedly attenuated IPAH-PASMC proliferation.

16 s for left heart disease; n = 421), atypical IPAH (>/=3 risk factors for left heart disease; n = 139)

17 ed with typical IPAH, patients with atypical IPAH and PH-HFpEF were older, had a higher body mass ind

18 th PH-HFpEF than typical IPAH; with atypical IPAH in between.

19 Patients with atypical IPAH share features of both typical IPAH and PH-HFpEF, s

20 nt clinical and survival differences between IPAH and PAH-Scl.

21 influence an individual's risk of developing IPAH.

22 s to design novel therapeutic strategies for IPAH.

23 Trb3 by phenamil is a potential therapy for IPAH and FPAH.

24 cursors were higher in peripheral blood from IPAH patients than in healthy controls and correlated wi

25 n of pulmonary artery endothelial cells from IPAH and control lungs in vitro revealed that oxygen con

26 pulmonary vascular fibroblasts isolated from IPAH patients exhibited upregulated glycolytic gene expr

27 tes to proliferation of PASMCs isolated from IPAH patients.

28 Lungs from IPAH patients versus unused donor controls revealed heig

29 a(2+)](cyt) by activating CaSR in PASMC from IPAH patients (in which CaSR is upregulated), but not in

30 We tested the hypothesis that PASMC from IPAH patients express more caveolin-1 (Cav-1) and caveol

31 In lung tissues and PASMC from IPAH patients, the mRNA and protein expression of TRPC3

32 ls were also detected in plasma samples from IPAH patients.

33 Human IPAH and control patient lung tissues and pulmonary arte

34 idiopathic pulmonary arterial hypertension (IPAH) involves hyperproliferative and apoptosis-resistan

35 Idiopathic pulmonary arterial hypertension (IPAH) is a cardiopulmonary disease characterized by cell

36 Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disorder characterized by pr

37 Idiopathic pulmonary arterial hypertension (IPAH) is pathogenetically related to low levels of the v

38 Idiopathic pulmonary arterial hypertension (IPAH) is usually without an identified genetic cause, de

39 idiopathic pulmonary arterial hypertension (IPAH) lung tissue and cultured smooth muscle cells.

40 idiopathic pulmonary arterial hypertension (IPAH) patients, hypoxia-exposed mice, and monocrotaline

41 Idiopathic pulmonary arterial hypertension (IPAH) results in increased right ventricular (RV) worklo

42 idiopathic pulmonary arterial hypertension (IPAH), the latter groups representing pathologically rel

43 idiopathic pulmonary arterial hypertension (IPAH), whereas a rise in cytosolic Ca2+ concentration tr

44 idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis

45 idiopathic pulmonary arterial hypertension (IPAH).

46 idiopathic pulmonary arterial hypertension (IPAH).

47 idiopathic pulmonary arterial hypertension (IPAH).

48 idiopathic pulmonary arterial hypertension (IPAH).

49 idiopathic pulmonary arterial hypertension (IPAH).

50 idiopathic pulmonary arterial hypertension (IPAH).

51 idiopathic pulmonary arterial hypertension (IPAH).

52 idiopathic pulmonary arterial hypertension (IPAH).

53 idiopathic pulmonary arterial hypertension (IPAH).

54 idiopathic pulmonary arterial hypertension (IPAH).

55 idiopathic pulmonary arterial hypertension (IPAH).

56 idiopathic pulmonary arterial hypertension (IPAH).

57 idiopathic pulmonary arterial hypertension (IPAH).

58 idiopathic pulmonary arterial hypertension (IPAH).

59 idiopathic pulmonary arterial hypertension (IPAH-ECs) have greater HIF-1alpha expression and transcr

60 idiopathic pulmonary arterial hypertension [IPAH]) or post-capillary (as seen in heart failure with

61 that may be hereditable (HPAH), idiopathic (IPAH), or associated with either drug-toxin exposures or

62 In IPAH/FPAH patients, 78 (37%) patients were acute respond

63 cits, whereas chamber dilation was absent in IPAH (+37+/-10% versus +1+/-8%, P=0.004, and +19+/-4% ve

64 ent evidence that the HA that accumulates in IPAH plexigenic lesions is a pathological form of HA in

65 e found increased stimulated Wnt activity in IPAH versus controls.

66 variants of unknown significance in BMPR2 in IPAH/HPAH, fenfluramine exposure, and PAH associated wit

67 Iron deficiency is common in IPAH patients and associated with disease severity and p

68 dipine-mediated increase in [Ca(2+)](cyt) in IPAH-PASMC was concentration dependent with a half maxim

69 e CaSR-mediated increase in [Ca(2+)](cyt) in IPAH-PASMC; however, the nondihydropyridine blockers, su

70 A pathway-based analysis of WES data in IPAH demonstrated multiple rare GVs that converge on key

71 s factor-stimulated gene 6, were detected in IPAH lung tissue.

72 er WES can also accelerate gene discovery in IPAH remains unknown.

73 ct of bosentan was significantly enhanced in IPAH-PASMCs in comparison with normal PASMCs.

74 increase in Cav-1 and caveolae expression in IPAH-PASMC.

75 There is phenotypic heterogeneity in IPAH, with a minority of patients showing long-term impr

76 hat the percentage of -254G/G homozygotes in IPAH patients was 2.85 times that of normal subjects.

77 and pulmonary vascular medial hypertrophy in IPAH patients.

78 ne biosynthetic pathway flux is increased in IPAH and drives OGT-facilitated PASMC proliferation thro

79 Finally, mitochondria numbers increased in IPAH-ECs with knockdown of HIF-1alpha.

80 rease susceptibility to small vessel loss in IPAH.

81 ume relations were prospectively measured in IPAH (n=9) and SSc-PAH (n=15) patients at rest and durin

82 ly with quantitative RV MVO2 measurements in IPAH.

83 ly as an index of RV oxidative metabolism in IPAH patients.

84 nfirmed increased lung glucose metabolism in IPAH.

85 account for lower numbers of mitochondria in IPAH-ECs.

86 of manganese superoxide dismutase (MnSOD) in IPAH-ECs paralleled increased HIF-1alpha levels and smal

87 The increased proliferation observed in IPAH PASMCs was directly impacted by proteolytic activat

88 gnificant survival advantage was observed in IPAH patients who started warfarin.

89 Partial knockdown of OGT in IPAH PASMCs resulted in reduced global O-linked beta-N-a

90 establish a novel regulatory role for OGT in IPAH, shed a new light on our understanding of the disea

91 ae expression and altered cell physiology in IPAH contrast with previous results obtained in various

92 rmalities of bioenergetics may be present in IPAH.

93 evels of resident endothelial progenitors in IPAH pulmonary arteries were comparable to those of heal

94 glucose metabolism and cell proliferation in IPAH has not been elucidated.

95 lism and smooth muscle cell proliferation in IPAH.

96 Hepcidin was inappropriately raised in IPAH independent of the inflammatory marker interleukin-

97 function increased at faster heart rates in IPAH patients, but were markedly blunted in SSc-PAH.

98 vascular inflammatory cells are recruited in IPAH pathogenesis, we hypothesized that reduced BMPR2 en

99 helial progenitors to vascular remodeling in IPAH.

100 cellular ATP did not change significantly in IPAH cells under hypoxia, whereas ATP decreased 35% in c

101 Knockdown of CaSR with siRNA in IPAH-PASMC significantly inhibited the nifedipine-induce

102 e allele frequency of the -254(C-->G) SNP in IPAH patients (12%) was significantly higher than in nor

103 t of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evalua

104 ersed the increased CCE and DNA synthesis in IPAH-PASMC.

105 rols revealed significantly higher uptake in IPAH lungs as compared with controls, confirming that th

106 d an expansion of LV end-diastolic volume in IPAH (+7%; P < 0.05), whereas end-diastolic pressure con

107 was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or i

108 d during atrial pacing in patients with mild IPAH (n = 10) compared with patients with isolated LV di

109 AH (VR-PAH) versus vasodilator-nonresponsive IPAH (VN-PAH).

110 Patients with nonsevere IPAH (pulmonary artery pressure mean 29 +/- 5 mm Hg) and

111 or reduced HIF-1alpha expression in normoxic IPAH-ECs.

112 irculating sTfR levels were raised in 63% of IPAH patients, indicating significant iron deficiency.

113 are substantial changes in bioenergetics of IPAH endothelial cells, which may have consequences for

114 angiogenic precursors is a characteristic of IPAH and may participate in the pulmonary vascular remod

115 in vitro revealed that oxygen consumption of IPAH cells was decreased, especially in state 3 respirat

116 tand the role of BMPR2 in the development of IPAH, we examined the phenotype of BMPR2(+/-) mice and t

117 roach to attenuate disease manifestations of IPAH.

118 d agonist-activated Ca2+ influx in PASMCs of IPAH patients harboring the -254G allele.

119 nd may be significant in the pathogenesis of IPAH.

120 from CD34+ CD133+ bone marrow precursors of IPAH patients secreted high levels of matrix metalloprot

121 roximately 3-fold greater glycolytic rate of IPAH cells.

122 the primary role for energy requirements of IPAH cells was provided by the approximately 3-fold grea

123 edispose individuals to an increased risk of IPAH by linking abnormal TRPC6 transcription to nuclear

124 d nitric oxide production in supernatants of IPAH-ECs.

125 ial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regress

126 tenuated CCE, and inhibited DNA synthesis of IPAH-PASMC.

127 Treatment of IPAH-PASMC with agents that deplete membrane cholesterol

128 mation, CCE, and DNA synthesis; treatment of IPAH-PASMC with siRNA targeted to Cav-1 produced the opp

129 VO2) of the hypertrophied right ventricle of IPAH patients can be measured using PET and (15)O-labele

130 also be determined in the right ventricle of IPAH patients from the clearance of (11)C-acetate, a sim

131 The greater effect of bosentan on IPAH-PASMCs than on normal PASMCs suggests that increase

132 e (SV/PP) and prospectively gathered data on IPAH patients who underwent a right heart catheterizatio

133 ith [18F]fluoro-deoxy-D-glucose performed on IPAH patients and healthy controls revealed significantl

134 patient populations with either PH-HFpEF or IPAH.

135 s compared with that in patients with IPF or IPAH, with adjustment for demographic and clinical param

136 he procedure compared with those with IPF or IPAH.

137 luable AVT, 212 had idiopathic/familial PAH (IPAH/FPAH) and 105 had PAH associated with congenital he

138 0 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score: 3.27+/-1.22), and 2 patients with conn

139 AH) and approximately 30% of idiopathic PAH (IPAH) patients.

140 ith PAH and 14 patients with idiopathic PAH (IPAH) was subjected to reverse transcriptase-polymerase

141 ntially worse prognosis than idiopathic PAH (IPAH), even though many measures of resting RV function

142 es compared with the idiopathic form of PAH (IPAH).

143 pathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and potentially fatal disease lin

144 Also, in pediatric IPAH, the Sitbon criteria are the criteria of choice to

145 whether GVs differ in vasodilator-responsive IPAH (VR-PAH) versus vasodilator-nonresponsive IPAH (VN-

146 sure-volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7), as well as SSc without PH (

147 ects and patients with Eisenmenger syndrome, IPAH lungs contained perivascular tLTs, comprising B- an

148 poses a greater pulmonary vascular load than IPAH and leads to worse RV contractile function.

149 IPF group (log-rank P = 0.21) and 79% in the IPAH group (P = 0.38).

150 Moreover, of the IPAH/FPAH patients judged by the treating physician as a

151 )FDG uptake and metabolism varied within the IPAH population and within the lungs of individual patie

152 n and caveolae expression thus contribute to IPAH-PASMC pathophysiology.

153 PR2 penetrance and genetic susceptibility to IPAH.

154 ed 1,369 genes with 1,580 variants unique to IPAH.

155 ) channel blockers (eg, nifedipine) to treat IPAH patients with upregulated CaSR in PASMC may exacerb

156 atypical IPAH share features of both typical IPAH and PH-HFpEF, suggesting that there may be a contin

157 unced in patients with PH-HFpEF than typical IPAH; with atypical IPAH in between.

158 treatment responses in patients with typical IPAH (<3 risk factors for left heart disease; n = 421),

159 Compared with typical IPAH, patients with atypical IPAH and PH-HFpEF were olde

160 t to identify gene variants (GVs) underlying IPAH and determine whether GVs differ in vasodilator-res

161 ence of clinical worsening in CTD-PAH versus IPAH (P for interaction = 0.012), but there was no diffe

162 ctile reserve is depressed in SSc-PAH versus IPAH subjects, associated with reduced calcium recycling

163 e in treatment effect on 6MWD in CTD-PAH vs. IPAH, -17.3 m; 90% confidence interval, -31.3 to -3.3; P

164 ntractility (end-systolic elastance) whereas IPAH did (P<0.001).

165 oderma (38%), 23 with IPF (33%), and 14 with IPAH (37%) died.

166 l data from 91 consecutive patients (41 with IPAH and 50 with PAH-Scl).

167 827 participants with CTD-PAH and 1,935 with IPAH from 11 RCTs.

168 TRPC6 gene promoter that are associated with IPAH and have functional significance in regulating TRPC

169 sponse to Ach and prognosis of children with IPAH.

170 dysfunction is worse in SScPAH compared with IPAH at similar afterload, and may be because of intrins

171 was less effective in CTD-PAH compared with IPAH in terms of increasing 6MWD and preventing clinical

172 ve greater vascular stiffening compared with IPAH, RV contractility was more depressed (Ees=0.8+/-0.3

173 Subcutaneous injection of NOD SCID mice with IPAH CFU-ECs within Matrigel plugs, but not with control

174 t versus placebo compared with patients with IPAH (difference in treatment effect on 6MWD in CTD-PAH

175 yt) was enhanced in PASMC from patients with IPAH and animals with experimental pulmonary hypertensio

176 uring pacing at 120 per minute patients with IPAH and DD decreased their stroke volume (-25% and -30%

177 ulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH.

178 Survival rates of patients with IPAH and other forms of PAH were compared by the use of

179 addition, approximately 20% of patients with IPAH carry mutations in BMPR2.

180 Some patients with IPAH exhibit increased lung (18)FDG uptake.

181 Two of 14 (14%) patients with IPAH exhibited BMPR2 point mutations, whereas none showe

182 The prognosis of patients with IPAH is difficult to predict, despite knowledge of clini

183 DNA isolated from 12 unrelated patients with IPAH lacking BMPR2 mutations.

184 March 30, 2010, 75 consecutive patients with IPAH underwent 6MW test and were included in the analysi

185 RPC6 expression in PASMCs from patients with IPAH was greater than in normal PASMCs, and the antiprol

186 s more likely to die than were patients with IPAH, after controlling for the presence of pericardial

187 output (+11%; P < 0.05) in the patients with IPAH, but not in patients with DD and control subjects.

188 s specifically in the lungs of patients with IPAH, providing new evidence of immunological mechanisms

189 ted with a survival benefit in patients with IPAH, supporting current treatment recommendations.

190 table and approximately 15% of patients with IPAH, their low penetrance ( approximately 20%) suggests

191 In patients with IPAH, there was a significantly better 3-year survival (

192 increased exercise capacity in patients with IPAH, with no significant changes in subjects with assoc

193 clinical worsening and TCW in patients with IPAH.

194 donors, patients with IPF, and patients with IPAH.

195 (sTfR), was investigated in 98 patients with IPAH.

196 lls of pulmonary arteries from patients with IPAH.

197 nts with PAH-Scl compared with patients with IPAH.

198 dent predictor of mortality in patients with IPAH.

199 in the overgrowth of PASMCs in patients with IPAH.

200 ndothelial cells isolated from patients with IPAH.

201 clinical worsening and TCW in patients with IPAH.

202 e-exome sequencing (WES) on 36 patients with IPAH: 17 with VR-PAH and 19 with VN-PAH.

203 6.6 mm Hg versus 54.4 mm Hg in patients with IPAH; P = 0.002) despite similar levels of cardiac dysfu

204 interval [95% CI] 0.74-3.93) and those with IPAH (RR 1.52, 95% CI 0.59-3.96), but the differences we

205 95.1% and 83.6%, respectively, in those with IPAH.

206 lescents (mean age: 10.4 +/- 5.5 years) with IPAH were included in the study.