Pulmonary Hypertension: Molecular Mechanisms and Clinical Studies
Joseph Adu-Amankwaah , Qiang You , Xiaoer Liu , Jiayi Jiang , Dongqi Yang , Kuntao Liu , Jinxiang Yuan , Yanfang Wang , Qinghua Hu , Rubin Tan
MedComm ›› 2025, Vol. 6 ›› Issue (3) : e70134
Pulmonary Hypertension: Molecular Mechanisms and Clinical Studies
Pulmonary hypertension (PH) stands as a tumor paradigm cardiovascular disease marked by hyperproliferation of cells and vascular remodeling, culminating in heart failure. Complex genetic and epigenetic mechanisms collectively contribute to the disruption of pulmonary vascular homeostasis. In recent years, advancements in research technology have identified numerous gene deletions and mutations, in addition to bone morphogenetic protein receptor type 2, that are closely associated with the vascular remodeling process in PH. Additionally, epigenetic modifications such as RNA methylation, DNA methylation, histone modification, and noncoding RNAs have been shown to precisely regulate PH molecular networks in a cell-type-specific manner, emerging as potential biomarkers and therapeutic targets. This review summarizes and analyzes the roles and molecular mechanisms of currently identified genes and epigenetic factors in PH, emphasizing the pivotal role of long ncRNAs in its regulation. Additionally, it examines current clinical and preclinical therapies for PH targeting these genes and epigenetic factors and explores potential new treatment strategies.
clinical therapeutics / epigenetic / genetic / noncoding RNAs / pulmonary hypertension
| [1] |
|
| [2] |
|
| [3] |
|
| [4] |
|
| [5] |
|
| [6] |
|
| [7] |
|
| [8] |
|
| [9] |
|
| [10] |
|
| [11] |
|
| [12] |
|
| [13] |
|
| [14] |
|
| [15] |
|
| [16] |
|
| [17] |
|
| [18] |
|
| [19] |
|
| [20] |
|
| [21] |
|
| [22] |
|
| [23] |
|
| [24] |
|
| [25] |
|
| [26] |
|
| [27] |
|
| [28] |
|
| [29] |
|
| [30] |
|
| [31] |
|
| [32] |
|
| [33] |
|
| [34] |
|
| [35] |
|
| [36] |
|
| [37] |
|
| [38] |
|
| [39] |
|
| [40] |
|
| [41] |
|
| [42] |
|
| [43] |
|
| [44] |
|
| [45] |
|
| [46] |
|
| [47] |
|
| [48] |
|
| [49] |
|
| [50] |
|
| [51] |
|
| [52] |
|
| [53] |
|
| [54] |
|
| [55] |
|
| [56] |
|
| [57] |
|
| [58] |
|
| [59] |
|
| [60] |
|
| [61] |
|
| [62] |
|
| [63] |
|
| [64] |
|
| [65] |
|
| [66] |
|
| [67] |
|
| [68] |
|
| [69] |
|
| [70] |
|
| [71] |
|
| [72] |
|
| [73] |
|
| [74] |
|
| [75] |
|
| [76] |
|
| [77] |
|
| [78] |
|
| [79] |
|
| [80] |
|
| [81] |
|
| [82] |
|
| [83] |
|
| [84] |
|
| [85] |
|
| [86] |
|
| [87] |
|
| [88] |
|
| [89] |
|
| [90] |
|
| [91] |
|
| [92] |
|
| [93] |
|
| [94] |
|
| [95] |
|
| [96] |
|
| [97] |
|
| [98] |
|
| [99] |
|
| [100] |
|
| [101] |
|
| [102] |
|
| [103] |
|
| [104] |
|
| [105] |
|
| [106] |
|
| [107] |
|
| [108] |
|
| [109] |
|
| [110] |
|
| [111] |
|
| [112] |
|
| [113] |
|
| [114] |
|
| [115] |
|
| [116] |
|
| [117] |
|
| [118] |
|
| [119] |
|
| [120] |
|
| [121] |
|
| [122] |
|
| [123] |
|
| [124] |
|
| [125] |
|
| [126] |
|
| [127] |
|
| [128] |
|
| [129] |
|
| [130] |
|
| [131] |
|
| [132] |
|
| [133] |
|
| [134] |
|
| [135] |
|
| [136] |
|
| [137] |
|
| [138] |
|
| [139] |
|
| [140] |
|
| [141] |
|
| [142] |
|
| [143] |
|
| [144] |
|
| [145] |
|
| [146] |
|
| [147] |
|
| [148] |
|
| [149] |
|
| [150] |
|
| [151] |
|
| [152] |
|
| [153] |
|
| [154] |
|
| [155] |
|
| [156] |
|
| [157] |
|
| [158] |
|
| [159] |
|
| [160] |
|
| [161] |
|
| [162] |
|
| [163] |
|
| [164] |
|
| [165] |
|
| [166] |
|
| [167] |
|
| [168] |
|
| [169] |
|
| [170] |
|
| [171] |
|
| [172] |
|
| [173] |
|
| [174] |
|
| [175] |
|
| [176] |
|
| [177] |
|
| [178] |
|
| [179] |
|
| [180] |
|
| [181] |
|
| [182] |
|
| [183] |
|
| [184] |
|
| [185] |
|
| [186] |
|
| [187] |
|
| [188] |
|
| [189] |
|
| [190] |
|
| [191] |
|
| [192] |
|
| [193] |
|
| [194] |
|
| [195] |
|
| [196] |
|
| [197] |
|
| [198] |
|
| [199] |
|
| [200] |
|
| [201] |
|
| [202] |
|
| [203] |
|
| [204] |
|
| [205] |
|
| [206] |
|
| [207] |
|
| [208] |
|
| [209] |
|
| [210] |
|
| [211] |
|
| [212] |
|
| [213] |
|
| [214] |
|
| [215] |
|
| [216] |
|
| [217] |
|
| [218] |
|
| [219] |
|
| [220] |
|
| [221] |
|
| [222] |
|
| [223] |
|
| [224] |
|
| [225] |
|
| [226] |
|
| [227] |
|
| [228] |
|
| [229] |
|
| [230] |
|
| [231] |
|
| [232] |
|
| [233] |
|
| [234] |
|
| [235] |
|
| [236] |
|
| [237] |
|
| [238] |
|
| [239] |
|
| [240] |
|
| [241] |
|
| [242] |
|
| [243] |
|
| [244] |
|
| [245] |
|
| [246] |
|
| [247] |
|
| [248] |
|
| [249] |
|
| [250] |
|
| [251] |
|
| [252] |
|
| [253] |
|
| [254] |
|
| [255] |
|
| [256] |
|
| [257] |
|
| [258] |
|
| [259] |
|
| [260] |
|
| [261] |
|
| [262] |
|
| [263] |
|
| [264] |
|
| [265] |
|
| [266] |
|
| [267] |
|
| [268] |
|
| [269] |
|
| [270] |
|
| [271] |
|
| [272] |
|
| [273] |
|
| [274] |
|
| [275] |
|
| [276] |
|
| [277] |
|
| [278] |
|
| [279] |
|
| [280] |
|
| [281] |
|
| [282] |
|
| [283] |
|
| [284] |
|
| [285] |
|
| [286] |
|
| [287] |
|
| [288] |
|
| [289] |
|
| [290] |
|
| [291] |
|
| [292] |
|
| [293] |
|
| [294] |
|
| [295] |
|
| [296] |
|
| [297] |
|
| [298] |
|
| [299] |
|
| [300] |
|
| [301] |
|
| [302] |
|
| [303] |
|
| [304] |
|
| [305] |
|
| [306] |
|
| [307] |
|
| [308] |
|
| [309] |
|
| [310] |
|
| [311] |
|
| [312] |
|
| [313] |
|
| [314] |
|
| [315] |
|
| [316] |
|
| [317] |
|
| [318] |
|
| [319] |
|
| [320] |
|
| [321] |
|
| [322] |
|
| [323] |
|
| [324] |
|
| [325] |
|
| [326] |
|
| [327] |
|
| [328] |
|
| [329] |
|
| [330] |
|
| [331] |
|
| [332] |
|
| [333] |
|
| [334] |
|
| [335] |
|
| [336] |
|
| [337] |
|
| [338] |
|
| [339] |
|
| [340] |
|
| [341] |
|
| [342] |
|
| [343] |
|
| [344] |
|
| [345] |
|
| [346] |
|
| [347] |
|
| [348] |
|
| [349] |
|
| [350] |
|
| [351] |
|
| [352] |
|
| [353] |
|
| [354] |
|
| [355] |
|
| [356] |
|
| [357] |
|
| [358] |
|
| [359] |
|
| [360] |
|
| [361] |
|
| [362] |
|
| [363] |
|
| [364] |
|
| [365] |
|
| [366] |
|
| [367] |
|
| [368] |
|
| [369] |
|
| [370] |
|
| [371] |
|
| [372] |
|
| [373] |
|
| [374] |
|
| [375] |
|
| [376] |
|
| [377] |
|
| [378] |
|
| [379] |
|
| [380] |
|
| [381] |
|
| [382] |
|
| [383] |
|
| [384] |
|
| [385] |
|
| [386] |
|
| [387] |
|
| [388] |
|
| [389] |
|
| [390] |
|
| [391] |
|
| [392] |
|
| [393] |
|
| [394] |
|
| [395] |
|
| [396] |
|
| [397] |
|
| [398] |
|
| [399] |
|
| [400] |
|
| [401] |
|
| [402] |
|
| [403] |
|
| [404] |
|
| [405] |
|
| [406] |
|
| [407] |
|
| [408] |
|
| [409] |
|
| [410] |
|
| [411] |
|
| [412] |
|
| [413] |
|
| [414] |
|
| [415] |
|
| [416] |
|
| [417] |
|
| [418] |
|
| [419] |
|
| [420] |
|
| [421] |
|
| [422] |
|
| [423] |
|
| [424] |
|
| [425] |
|
| [426] |
|
| [427] |
|
| [428] |
|
| [429] |
|
| [430] |
|
| [431] |
|
| [432] |
|
| [433] |
|
| [434] |
|
| [435] |
|
| [436] |
|
| [437] |
|
| [438] |
|
| [439] |
|
| [440] |
|
| [441] |
|
| [442] |
|
| [443] |
|
| [444] |
|
| [445] |
|
| [446] |
|
| [447] |
|
| [448] |
|
| [449] |
|
| [450] |
|
| [451] |
|
| [452] |
|
| [453] |
|
| [454] |
|
| [455] |
|
| [456] |
|
| [457] |
|
| [458] |
|
| [459] |
|
| [460] |
|
| [461] |
|
| [462] |
|
| [463] |
|
| [464] |
|
| [465] |
|
| [466] |
|
| [467] |
|
| [468] |
|
| [469] |
|
| [470] |
|
| [471] |
|
| [472] |
|
| [473] |
|
| [474] |
|
| [475] |
|
| [476] |
|
| [477] |
|
| [478] |
|
| [479] |
|
| [480] |
|
| [481] |
|
| [482] |
|
| [483] |
|
| [484] |
|
| [485] |
|
| [486] |
|
| [487] |
|
| [488] |
|
| [489] |
|
| [490] |
|
| [491] |
|
| [492] |
|
| [493] |
|
| [494] |
|
| [495] |
|
| [496] |
|
| [497] |
|
| [498] |
|
| [499] |
|
| [500] |
|
| [501] |
|
| [502] |
|
| [503] |
|
| [504] |
|
| [505] |
|
| [506] |
|
| [507] |
|
| [508] |
|
| [509] |
|
| [510] |
|
| [511] |
|
| [512] |
|
| [513] |
|
| [514] |
|
| [515] |
|
| [516] |
|
| [517] |
|
| [518] |
|
| [519] |
|
| [520] |
|
| [521] |
|
| [522] |
|
| [523] |
|
| [524] |
|
| [525] |
|
| [526] |
|
| [527] |
|
| [528] |
|
| [529] |
|
| [530] |
|
| [531] |
|
| [532] |
|
| [533] |
Positioning imatinib for pulmonary arterial hypertension (PIPAH). ClinicalTrials.gov identifier: NCT04416750. Updated October 10, 2023. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT04416750. |
| [534] |
|
| [535] |
|
| [536] |
|
| [537] |
|
| [538] |
|
| [539] |
|
| [540] |
|
| [541] |
|
| [542] |
|
| [543] |
|
| [544] |
|
| [545] |
|
| [546] |
|
| [547] |
Tamoxifen therapy to treat pulmonary arterial hypertension (T2PAH). ClinicalTrials.gov identifier: NCT03528902. Updated August 07, 2024. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT03528902. |
| [548] |
Subcutaneous elafin in healthy subjects. ClinicalTrials.gov ClinicalTrials.gov. identifier: NCT03522935. Updated August 15, 2024. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT03522935. |
| [549] |
Pulmonary hypertension: assessment of cell therapy (PHACeT). ClinicalTrials.gov identifier: NCT00469027. Updated October 17, 2016. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT00469027. |
| [550] |
|
| [551] |
Study of angiogenic cell therapy for progressive pulmonary hypertension: intervention with repeat dosing of eNOS-enhanced EPCs (SAPPHIRE). ClinicalTrials.gov identifier: NCT03001414. Updated February 01, 2021. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT03001414 |
| [552] |
|
| [553] |
Apabetalone for pulmonary arterial hypertension: a pilot study (APPRoAcH-p). ClinicalTrials.gov identifier: NCT03655704. Updated April 25, 2022. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT03655704. |
| [554] |
|
| [555] |
|
| [556] |
Bardoxolone methyl evaluation in patients with pulmonary hypertension (PH)— LARIAT. ClinicalTrials.gov identifier: NCT02036970. Updated February 05, 2024. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT02036970. |
| [557] |
Bardoxolone methyl in patients with connective tissue disease-associated pulmonary arterial hypertension—CATALYST. ClinicalTrials.gov identifier: NCT02657356. Updated February 06, 2024. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT02657356. |
| [558] |
Extended access program to assess long-term safety of bardoxolone methyl in patients with pulmonary hypertension RANGER (RANGER). ClinicalTrials.gov identifier: NCT03068130. Updated February 06, 2021. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT03068130. |
| [559] |
|
| [560] |
A study of rodatristat ethyl in patients with pulmonary arterial hypertension (ELEVATE2). ClinicalTrials.gov identifier: NCT04712669. Updated November 05, 2023. Accessed January 28, 2025, https://clinicaltrials.gov/ct2/show/NCT04712669. |
| [561] |
|
| [562] |
|
| [563] |
|
| [564] |
|
| [565] |
|
| [566] |
|
| [567] |
|
2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.
/
| 〈 |
|
〉 |