ライフサイエンスコーパス: IPAH

1 IPAH may be associated with pulmonary endothelial dysfun

2 IPAH patient-derived PAE cells stimulate accumulation of

3 IPAH pulmonary artery endothelial cells had decreased mi

4 IPAH-PASMC exhibit increased glycosaminoglycan productio

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

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

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

8 Lung tissue samples from 4 SSc-PAH, 4 IPAH, and 4 failed donor specimens were obtained from th

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

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

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

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

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

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

15 Plexiform lesions and IPAH adventitia exhibited the greatest number of differe

16 Plexiform lesions and IPAH adventitia showed upregulation of genes involved in

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

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

19 were consistently increased in IPAH-PAs and IPAH-PAAFs, whereas HDAC2 and HDAC8 showed predominant l

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

21 A and HDAC inhibitors, which also attenuated IPAH-associated hyperproliferation and apoptosis-resista

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

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

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

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

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

27 r of vascular and inflammatory cells between IPAH lesions, which underlies the differential transcrip

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

29 and in various epithelial cell types in both IPAH and SSc-PAH, with epithelial-to-endothelial cell si

30 Conclusions: IPAH lesions express unique molecular transcript profile

31 influence an individual's risk of developing IPAH.

32 s to design novel therapeutic strategies for IPAH.

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

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

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

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

37 tes to proliferation of PASMCs isolated from IPAH patients.

38 Lungs from IPAH patients versus unused donor controls revealed heig

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

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

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

42 editing levels were analyzed in PASMCs from IPAH patients versus healthy controls.

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

44 Human IPAH and control patient lung tissues and pulmonary arte

45 idiopathic pulmonary arterial hypertension (IPAH) and PH associated with lung disease (PH-LD).

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

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

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

49 Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right hea

50 Idiopathic pulmonary arterial hypertension (IPAH) is characterized by extensive pulmonary vascular r

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

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

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

54 idiopathic pulmonary arterial hypertension (IPAH) patients and healthy donors.

55 idiopathic pulmonary arterial hypertension (IPAH) patients compared to those from healthy controls.

56 idiopathic pulmonary arterial hypertension (IPAH) patients, as well as from chronically hypoxic mice

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

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

59 idiopathic pulmonary arterial hypertension (IPAH), a devastating disease leading to right heart fail

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

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

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

63 idiopathic pulmonary arterial hypertension (IPAH).

64 idiopathic pulmonary arterial hypertension (IPAH).

65 idiopathic pulmonary arterial hypertension (IPAH).

66 idiopathic pulmonary arterial hypertension (IPAH).

67 idiopathic pulmonary arterial hypertension (IPAH).

68 idiopathic pulmonary arterial hypertension (IPAH).

69 idiopathic pulmonary arterial hypertension (IPAH).

70 idiopathic pulmonary arterial hypertension (IPAH).

71 idiopathic pulmonary arterial hypertension (IPAH).

72 idiopathic pulmonary arterial hypertension (IPAH).

73 idiopathic pulmonary arterial hypertension (IPAH).

74 Idiopathic Pulmonary Arterial Hypertension (IPAH).

75 idiopathic pulmonary arterial hypertension (IPAH).

76 idiopathic pulmonary arterial hypertension (IPAH).

77 idiopathic pulmonary arterial hypertension (IPAH).

78 idiopathic pulmonary arterial hypertension (IPAH).

79 idiopathic pulmonary arterial hypertension (IPAH).

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

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

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

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

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

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

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

87 intima+media hypertrophy, and adventitia) in IPAH lungs (n = 11) and compared these data with the int

88 of hypoxia-induced PH in mice as well as in IPAH, although SPARC plasma levels were not elevated in

89 Objectives: To study autoimmunity in IPAH using a large cross-sectional cohort.

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

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

92 enes and induced Foxp3(+) Treg conversion in IPAH T cells.

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

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

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

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

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

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

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

100 ide a rich molecular-structural framework in IPAH vascular lesions that inform novel biomarkers and t

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

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

103 and pulmonary vascular medial hypertrophy in IPAH patients.

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

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

106 AC1 and HDAC8 were consistently increased in IPAH-PAs and IPAH-PAAFs, whereas HDAC2 and HDAC8 showed

107 es dysregulation of class I HDAC isoforms in IPAH.

108 Reduced transcript levels of KLF2 in IPAH-PAAFs was augmented by HDAC8 siRNA and HDAC inhibit

109 Plexiform lesions in IPAH showed enrichment for 1) genes associated with tran

110 rease susceptibility to small vessel loss in IPAH.

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

112 ly with quantitative RV MVO2 measurements in IPAH.

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

114 nfirmed increased lung glucose metabolism in IPAH.

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

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

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

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

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

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

121 es to alleviate severe vascular pathology in IPAH and HPAH.

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

123 rmalities of bioenergetics may be present in IPAH.

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

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

126 lism and smooth muscle cell proliferation in IPAH.

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

128 autoantibodies were significantly raised in IPAH, and clustering demonstrated three distinct cluster

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

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

131 helial progenitors to vascular remodeling in IPAH.

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

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

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

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

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

137 regulate distinct subset of transcriptome in IPAH-PAAFs.

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

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

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

141 ught to test the hypothesis that microscopic IPAH vascular lesions express unique molecular profiles,

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

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

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

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

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

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

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

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

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

151 roach to attenuate disease manifestations of IPAH.

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

153 nd may be significant in the pathogenesis of IPAH.

154 molecular insights into the pathogenesis of IPAH.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

169 patient populations with either PH-HFpEF or IPAH.

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

171 he procedure compared with those with IPF or IPAH.

172 nhibitors were evaluated ex vivo (IPAH-PAAF, IPAH-PASMC) and in vivo (rat chronic hypoxia-induced PH

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

174 0 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score: 3.27+/-1.22), and 2 patients with conn

175 isolated from patients with idiopathic PAH (IPAH) and rodent models of pulmonary hypertension (PH):

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

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

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

179 rse outcomes than those with idiopathic PAH (IPAH).

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

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

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

183 A2-expressing cells in extensively remodeled IPAH-PAs.

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

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

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

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

188 ytometric immune profiling demonstrates that IPAH is associated with an altered humoral immune respon

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

190 esults: We detected 8,273 transcripts in the IPAH lesions and control lung pulmonary arteries.

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

192 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification a

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

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

195 PR2 penetrance and genetic susceptibility to IPAH.

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

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

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

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

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

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

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

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

204 g gene expression patterns in SSc-PAH versus IPAH lung tissues could inform the investigation of prec

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

206 expression patterns exist in SSc-PAH versus IPAH, with significant molecular differences suggesting

207 051) HDAC inhibitors were evaluated ex vivo (IPAH-PAAF, IPAH-PASMC) and in vivo (rat chronic hypoxia-

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

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

210 wnregulation of contractile machinery, while IPAH-PAAF display a hyperproliferative phenotype.

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

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

213 827 participants with CTD-PAH and 1,935 with IPAH from 11 RCTs.

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

215 sponse to Ach and prognosis of children with IPAH.

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

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

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

219 th heightened severity in HPAH compared with IPAH.

220 of dendritic cells/macrophages compared with IPAH.

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

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

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

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

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

226 of a significant proportion of patients with IPAH and is associated with clinical outcomes.

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

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

229 PASMCs from patients with IPAH displayed decreased levels of ADAR1 mRNA and isofor

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

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

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

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

234 lticenter study included adult patients with IPAH or PH-LD who underwent incidental CT imaging betwee

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

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

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

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

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

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

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

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

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

244 clinical worsening and TCW in patients with IPAH.

245 clinical worsening and TCW in patients with IPAH.

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

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

248 lls of pulmonary arteries from patients with IPAH.

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

250 dent predictor of mortality in patients with IPAH.

251 in the overgrowth of PASMCs in patients with IPAH.

252 l blood mononuclear cells from patients with IPAH.

253 ndothelial cells isolated from patients with IPAH.

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

255 6.6 mm Hg versus 54.4 mm Hg in patients with IPAH; P = 0.002) despite similar levels of cardiac dysfu

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

257 95.1% and 83.6%, respectively, in those with IPAH.

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