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  • Editorial
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11 November 2025

Microbiome Dysregulation and Inflammation: Key Players in Pulmonary Hypertension Pathophysiology

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA 94305, USA
Biomedicines2025, 13(11), 2750;https://doi.org/10.3390/biomedicines13112750
This article belongs to the Section Molecular and Translational Medicine
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Pulmonary hypertension (PH) is a fatal disease characterized by elevated pulmonary pressures, progressive pulmonary vascular remodeling, and right heart failure [1,2]. The burgeoning field of microbiome research has witnessed significant advancements in recent years, driven by technological innovations and collaborative research efforts [3,4]. Researchers have characterized gut microbial communities by utilizing state-of-the-art sequencing technologies, such as 16S rRNA gene sequencing and shotgun metagenomics, across multiple PH human and animal cohorts [5,6,7,8]. Growing evidence suggests that gut microbial changes contribute to PH through modulation of immune and metabolic pathways, connecting the gut–lung axis to PH pathogenesis [5,7]. The review paper titled “Pulmonary Hypertension and the Gut Microbiome” [9] provides a comprehensive summary of available experimental and clinical evidence, linking gut microbiome imbalances to the development and progression of PH, particularly the pulmonary arterial hypertension (PAH). The review describes how alterations in gut microbiome composition, including reduced microbial diversity, depletion of anti-inflammatory short-chain fatty acid (SCFA)-producing bacteria, and enrichment of proinflammatory species may impair gut barrier integrity, allowing for translocation of microbial metabolic products, such as lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO) into circulation. These microbial metabolites activate toll-like receptor 4 (TLR4) signaling, inflammatory cytokine release, and pathways involving serotonin and arginine metabolism, all of which contribute to endothelial dysfunction and pulmonary vascular remodeling in PH [10,11,12]. Moreover, human and animal studies reveal distinct gut microbiome profiles that predict PH presence and severity, with elevated microbial TMAO correlating with worse clinical outcomes [12,13]. The review also highlights emerging therapeutic targets, including probiotics, prebiotics, dietary modification, and fecal microbiota transplantation, as potential adjuncts to current vasodilator treatments for PH [14,15,16].
Besides the above paper in the Special Issue, which emphasized the role of serotonin in determining health outcomes, another review paper [17] from Prof. Cassidy Delaney’s group explored the multifaceted roles of serotonin signaling in normal lung development and in the pathogenesis of neonatal PH. Serotonin (5-hydroxytryptamine, 5-HT) is mainly synthesized in the gut, and the gut microbiome significantly influences serotonin production [18,19]. Serotonin acts as both a neurotransmitter and a vasoactive mediator that regulates pulmonary vascular tone and smooth muscle proliferation in the developing lung and PAH pathogenesis [12,17,18]. Serotonin contributes to PH through activation of 5-HT receptors (especially 5-HT1B/5-HT2A) and uptake via the serotonin transporter (SERT), leading to marked vasoconstriction and elevated pulmonary vascular resistance [18]. Elevated serotonin levels or enhanced SERT activity increase pulmonary vascular resistance, stimulate vascular remodeling, and contribute to persistent pulmonary hypertension of the newborn (PPHN), a life-threatening condition associated with intracardiac shunting and hypoxemia. The authors reviewed studies implicating maternal factors, such as selective serotonin reuptake inhibitor use and hypoxia, in altering serotonin homeostasis, which, in turn, exacerbates neonatal PH risk [20,21,22]. They also highlight that enhanced serotonin production, receptor activation, and transporter-mediated uptake converge to drive the vasoconstrictive and proliferative phenotype characteristic of PH [23,24], making the serotonin pathway an attractive therapeutic target. Overall, the review underscores serotonin as a critical developmental regulator and a promising target for preventing or treating neonatal PH.
A review of chronic thromboembolic pulmonary hypertension (CTEPH) pathobiology [25] and a case report about PAH-related spontaneous bacterial peritonitis (SBP) [26] were also included in the Special Issue. CTEPH, a rare but potentially surgical curable form of PH, arises when unresolved thrombi become fibrotic and obstruct pulmonary arteries, leading to pulmonary embolism (PE) and eventual right heart failure [27]. The review [25] highlights the interplay of multiple pathological processes, such as prothrombotic state, fibrinolysis resistance, defective angiogenesis, and chronic inflammation, on CTEPH risk [28,29,30]. Importantly, genetic factors, such as variants in fibrinogen [31] and ABO blood group [32], as well as contributors, including gut microbiome dysbiosis, low-grade infections, circulating microparticles, and plasma metabolic disturbances affecting lipid- and amino acid-signaling pathways, are all known to be associated with the pathobiology of CTEPH [12,33,34,35]. Despite these advances, the review emphasized that many pathways overlap with acute PE and venous thromboembolism, leaving the question of why only a minority of PE patients develop CTEPH unresolved. The authors conclude that integrating genetic, epigenetic, microbiome, and metabolomic research will be critical for guiding future preventive and therapeutic strategies for CTEPH. Although ascites is typically caused by cirrhosis, cardiac ascites accounts for ~3% of cases and rarely progresses to SBP due to the preserved opsonic and bactericidal activity of its protein-rich fluid [36,37,38]. This case report [26] describes a 75-year-old man with severe PAH who developed new-onset ascites complicated by SBP—a rare manifestation of right heart failure [39]. The patient presented with dyspnea and abdominal distension. Diagnostic paracentesis revealed a serum–ascites albumin gradient (SAAG) ≥1.1 g/dL and high protein content consistent with cardiac ascites [40,41], while a polymorphic nucleated cell count (PMN) of 663 cells/mm3 confirmed SBP [36,42]. Imaging and clinical data supported decompensated right heart failure secondary to PAH rather than liver cirrhosis. He was successfully treated with antibiotics, diuretics, and fluid restriction. This unique case underscores that PAH-related right heart failure can lead to portal hypertension, congestive hepatopathy, and susceptibility to SBP despite the traditionally low infection risk of cardiac ascites, and it calls for the development of management guidelines specific to SBP in non-cirrhotic ascites.
Finally, a research study [43] in the Special Issue explored the regulatory role and mechanism of N6-methyladenosine (m6A) RNA modification in PAH. m6A is the most abundant internal RNA modification in eukaryotic cells, and emerging evidence [44,45] shows that it plays a key regulatory role in PH by controlling gene expression and vascular remodeling. Using monocrotaline (MCT)-induced PAH rats, the authors performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq to map transcriptome-wide m6A changes and associated gene expression in pulmonary artery tissues. They identified 209 genes with significantly altered m6A peaks, revealing widespread hypermethylation and hypomethylation enriched in extracellular matrix (ECM) remodeling, MAPK, and PI3K/AKT signaling pathways, which are central to PAH pathogenesis [46,47,48]. Integration of m6A and transcriptomic data highlighted 42 key genes with concurrent changes in methylation and expression, among which Centromere Protein F (Cenpf) emerged as a hub gene that promotes pulmonary artery smooth muscle cell (PASMC) proliferation. The study also discovered a novel m6A reader, Leucine-Rich Pentatricopeptide Repeat Containing (Lrpprc), which was significantly downregulated in PAH. Further experiments showed that silencing Lrpprc enhanced PASMC proliferation and increased Cenpf expression, suggesting that Lrpprc negatively regulates vascular remodeling through m6A-dependent mechanisms. Overall, the findings provide a comprehensive map of m6A modifications in PAH pulmonary arteries, implicating dysregulated m6A signaling in abnormal PASMC growth and identifying potential epigenetic targets for therapeutic intervention. Although the work does not directly investigate the microbiome, the identified genes are closely connected to inflammatory processes that drive pulmonary vascular inflammation and remodeling in PAH.
In summary, the assembled reviews [9,17,25] in the Special Issue highlight how gut microbiome alterations, including loss of beneficial taxa and expansion of proinflammatory microbes, can elevate circulating metabolites (e.g., LPS, TMAO) and activate serotonin, TLR4, and other signaling pathways to modulate the immune/inflammatory responses that promote pulmonary vascular remodeling and PH progression. The case report found that PAH-related SBP [26], although rare, can be lethal if not properly treated with antibiotics and other treatments. The original study [43] demonstrates widespread m6A modifications in PAH pulmonary arteries, particularly in genes linked to vascular remodeling, inflammation, and cell proliferation, thereby revealing novel epigenetic targets for PH. Altogether, the collection proposes that the gut microbiota interacts with the lungs through the gut–lung axis, which is mediated through microbial metabolism and inflammatory signaling. While the gut microbiome has received considerable attention due to its profound impact on host physiology and health, recent studies have extended the investigation to various anatomical niches, including the upper airway [49,50] and lungs [7,8], which may impact PH pathogenesis and host response. An important outlook for the field is that microbiome and inflammation research is reframing PH as a systemic, immune–metabolic disease rather than an isolated pulmonary vascular disorder. Thus, microbial dysbiosis, inflammation, and intersection with molecular modifications in vascular cells are emerging as crucial and interlinked contributors to PH pathogenesis and attractive therapeutic targets.

Funding

This research received no external funding.

Conflicts of Interest

The author declares no conflicts of interest.

References

  1. Maron, B.A. Revised Definition of Pulmonary Hypertension and Approach to Management: A Clinical Primer. J. Am. Heart Assoc. 2023, 12, e029024. [Google Scholar] [CrossRef]
  2. Zhao, L.; Cunningham, C.M.; Hong, J.; Agarwal, S.; Yuan, K.; de Jesus Perez, V.A.; Nicolls, M.R. A Cross-Species and Sex-Specific Meta-Analysis of Transcriptomic Studies of Pulmonary Hypertension. Am. J. Respir. Cell Mol. Biol. 2025, 73, 427–440. [Google Scholar] [CrossRef]
  3. Berg, G.; Rybakova, D.; Fischer, D.; Cernava, T.; Vergès, M.-C.C.; Charles, T.; Chen, X.; Cocolin, L.; Eversole, K.; Corral, G.H.; et al. Microbiome Definition Re-Visited: Old Concepts and New Challenges. Microbiome 2020, 8, 103. [Google Scholar] [PubMed]
  4. Zhao, L.; Luo, J.-L.; Ali, M.K.; Spiekerkoetter, E.; Nicolls, M.R. The Human Respiratory Microbiome: Current Understandings and Future Directions. Am. J. Respir. Cell Mol. Biol. 2023, 68, 245–255. [Google Scholar] [CrossRef]
  5. Moutsoglou, D.M.; Tatah, J.; Prisco, S.Z.; Prins, K.W.; Staley, C.; Lopez, S.; Blake, M.; Teigen, L.; Kazmirczak, F.; Weir, E.K.; et al. Pulmonary Arterial Hypertension Patients Have a Proinflammatory Gut Microbiome and Altered Circulating Microbial Metabolites. Am. J. Respir. Crit. Care Med. 2023, 207, 740–756. [Google Scholar] [CrossRef]
  6. Ikubo, Y.; Sanada, T.J.; Hosomi, K.; Park, J.; Naito, A.; Shoji, H.; Misawa, T.; Suda, R.; Sekine, A.; Sugiura, T.; et al. Altered Gut Microbiota and Its Association with Inflammation in Patients with Chronic Thromboembolic Pulmonary Hypertension: A Single-Center Observational Study in Japan. BMC Pulm. Med. 2022, 22, 138. [Google Scholar] [CrossRef] [PubMed]
  7. Xie, J.; Zhang, X.; Cheng, L.; Deng, Y.; Ren, H.; Mu, M.; Zhao, L.; Mu, C.; Chen, J.; Liu, K.; et al. Integrated Multi-Omics Analysis of the Microbial Profile Characteristics Associated with Pulmonary Arterial Hypertension in Congenital Heart Disease. Microbiol. Spectr. 2024, 12, e0180824. [Google Scholar] [CrossRef]
  8. Marinho, Y.; Villarreal, E.S.; Aboagye, S.Y.; Williams, D.L.; Sun, J.; Silva, C.L.M.; Lutz, S.E.; Oliveira, S.D. Schistosomiasis-Associated Pulmonary Hypertension Unveils Disrupted Murine Gut-Lung Microbiome and Reduced Endoprotective Caveolin-1/BMPR2 Expression. Front. Immunol. 2023, 14, 1254762. [Google Scholar] [CrossRef]
  9. Mason, T.; Mukherjee, B.; Marino, P. Pulmonary Hypertension and the Gut Microbiome. Biomedicines 2024, 12, 169. [Google Scholar] [CrossRef]
  10. Chen, Y.-H.; Yuan, W.; Meng, L.-K.; Zhong, J.-C.; Liu, X.-Y. The Role and Mechanism of Gut Microbiota in Pulmonary Arterial Hypertension. Nutrients 2022, 14, 4278. [Google Scholar] [CrossRef]
  11. Wedgwood, S.; Warford, C.; Agvatisiri, S.R.; Thai, P.N.; Chiamvimonvat, N.; Kalanetra, K.M.; Lakshminrusimha, S.; Steinhorn, R.H.; Mills, D.A.; Underwood, M.A. The Developing Gut-Lung Axis: Postnatal Growth Restriction, Intestinal Dysbiosis, and Pulmonary Hypertension in a Rodent Model. Pediatr. Res. 2020, 87, 472–479. [Google Scholar] [CrossRef]
  12. Kim, S.; Rigatto, K.; Gazzana, M.B.; Knorst, M.M.; Richards, E.M.; Pepine, C.J.; Raizada, M.K. Altered Gut Microbiome Profile in Patients With Pulmonary Arterial Hypertension. Hypertension 2020, 75, 1063–1071. [Google Scholar] [CrossRef]
  13. Zhu, W.; Gregory, J.C.; Org, E.; Buffa, J.A.; Gupta, N.; Wang, Z.; Li, L.; Fu, X.; Wu, Y.; Mehrabian, M.; et al. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell 2016, 165, 111–124. [Google Scholar] [CrossRef]
  14. Liu, Y.; Fatheree, N.Y.; Mangalat, N.; Rhoads, J.M. Lactobacillus Reuteri Strains Reduce Incidence and Severity of Experimental Necrotizing Enterocolitis via Modulation of TLR4 and NF-κB Signaling in the Intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 302, G608–G617. [Google Scholar] [CrossRef] [PubMed]
  15. Zhou, D.-D.; Luo, M.; Shang, A.; Mao, Q.-Q.; Li, B.-Y.; Gan, R.-Y.; Li, H.-B. Antioxidant Food Components for the Prevention and Treatment of Cardiovascular Diseases: Effects, Mechanisms, and Clinical Studies. Oxid. Med. Cell. Longev. 2021, 2021, 6627355. [Google Scholar] [CrossRef] [PubMed]
  16. Sharma, R.K.; Oliveira, A.C.; Yang, T.; Karas, M.M.; Li, J.; Lobaton, G.O.; Aquino, V.P.; Robles-Vera, I.; de Kloet, A.D.; Krause, E.G.; et al. Gut Pathology and Its Rescue by ACE2 (angiotensin-Converting Enzyme 2) in Hypoxia-Induced Pulmonary Hypertension. Hypertension 2020, 76, 206–216. [Google Scholar] [CrossRef]
  17. Archambault, J.L.; Delaney, C.A. A Review of Serotonin in the Developing Lung and Neonatal Pulmonary Hypertension. Biomedicines 2023, 11, 3049. [Google Scholar] [CrossRef]
  18. MacLean, M.M.R. The Serotonin Hypothesis in Pulmonary Hypertension Revisited: Targets for Novel Therapies (2017 Grover Conference Series). Pulm. Circ. 2018, 8, 2045894018759125. [Google Scholar] [CrossRef]
  19. Bellono, N.W.; Bayrer, J.R.; Leitch, D.B.; Castro, J.; Zhang, C.; O’Donnell, T.A.; Brierley, S.M.; Ingraham, H.A.; Julius, D. Enterochromaffin Cells Are Gut Chemosensors That Couple to Sensory Neural Pathways. Cell 2017, 170, 185–198.e16. [Google Scholar] [CrossRef]
  20. Hooper, C.W.; Delaney, C.; Streeter, T.; Yarboro, M.T.; Poole, S.; Brown, N.; Slaughter, J.C.; Cotton, R.B.; Reese, J.; Shelton, E.L. Selective Serotonin Reuptake Inhibitor Exposure Constricts the Mouse Ductus Arteriosus in Utero. Am. J. Physiol. Heart Circ. Physiol. 2016, 311, H572–H581. [Google Scholar] [CrossRef] [PubMed]
  21. Delaney, C.; Gien, J.; Roe, G.; Isenberg, N.; Kailey, J.; Abman, S.H. Serotonin Contributes to High Pulmonary Vascular Tone in a Sheep Model of Persistent Pulmonary Hypertension of the Newborn. Am. J. Physiol. Lung Cell. Mol. Physiol. 2013, 304, L894–L901. [Google Scholar] [CrossRef]
  22. Goyal, R.; Papamatheakis, D.G.; Loftin, M.; Vrancken, K.; Dawson, A.S.; Osman, N.J.; Blood, A.B.; Pearce, W.J.; Longo, L.D.; Wilson, S.M. Long-Term Maternal Hypoxia: The Role of Extracellular Ca2+ Entry During Serotonin-Mediated Contractility in Fetal Ovine Pulmonary Arteries. Reprod. Sci. 2011, 18, 948–962. [Google Scholar] [CrossRef] [PubMed]
  23. Launay, J.-M.; Hervé, P.; Peoc’h, K.; Tournois, C.; Callebert, J.; Nebigil, C.G.; Etienne, N.; Drouet, L.; Humbert, M.; Simonneau, G.; et al. Function of the Serotonin 5-Hydroxytryptamine 2B Receptor in Pulmonary Hypertension. Nat. Med. 2002, 8, 1129–1135. [Google Scholar] [CrossRef]
  24. Lawrie, A.; Spiekerkoetter, E.; Martinez, E.C.; Ambartsumian, N.; Sheward, W.J.; MacLean, M.R.; Harmar, A.J.; Schmidt, A.-M.; Lukanidin, E.; Rabinovitch, M. Interdependent Serotonin Transporter and Receptor Pathways Regulate S100A4/Mts1, a Gene Associated with Pulmonary Vascular Disease. Circ. Res. 2005, 97, 227–235. [Google Scholar] [CrossRef]
  25. Ghani, H.; Pepke-Zaba, J. Chronic Thromboembolic Pulmonary Hypertension: A Review of the Multifaceted Pathobiology. Biomedicines 2023, 12, 46. [Google Scholar] [CrossRef] [PubMed]
  26. Beckmann, T.; Pavlatos, N.; Kalra, D.K. Spontaneous Bacterial Peritonitis: A Rare Complication of Pulmonary Arterial Hypertension. Biomedicines 2024, 12, 1389. [Google Scholar] [CrossRef] [PubMed]
  27. McNeil, K.; Dunning, J. Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Heart 2007, 93, 1152–1158. [Google Scholar] [CrossRef]
  28. Remková, A.; Šimková, I.; Valkovičová, T. Platelet Abnormalities in Chronic Thromboembolic Pulmonary Hypertension. Int. J. Clin. Exp. Med. 2015, 8, 9700–9707. [Google Scholar]
  29. Wolf, M.; Boyer-Neumann, C.; Parent, F.; Eschwege, V.; Jaillet, H.; Meyer, D.; Simonneau, G. Thrombotic Risk Factors in Pulmonary Hypertension. Eur. Respir. J. 2000, 15, 395–399. [Google Scholar] [CrossRef]
  30. Hadinnapola, C.M.; Southwood, M.; Hernández-Sánchez, J.; Bunclark, K.; Newnham, M.; Swietlik, E.M.; Cannon, J.; Preston, S.D.; Sheares, K.; Taboada, D.; et al. Angiopoietin 2 and hsCRP Are Associated with Pulmonary Hemodynamics and Long-Term Mortality Respectively in CTEPH-Results from a Prospective Discovery and Validation Biomarker Study. J. Heart Lung Transplant. 2023, 42, 398–405. [Google Scholar] [CrossRef]
  31. Morris, T.A.; Marsh, J.J.; Chiles, P.G.; Magaña, M.M.; Liang, N.-C.; Soler, X.; Desantis, D.J.; Ngo, D.; Woods, V.L., Jr. High Prevalence of Dysfibrinogenemia among Patients with Chronic Thromboembolic Pulmonary Hypertension. Blood 2009, 114, 1929–1936. [Google Scholar] [CrossRef]
  32. Newnham, M.; South, K.; Bleda, M.; Auger, W.R.; Barberà, J.A.; Bogaard, H.; Bunclark, K.; Cannon, J.E.; Delcroix, M.; Hadinnapola, C.; et al. The ADAMTS13-VWF Axis Is Dysregulated in Chronic Thromboembolic Pulmonary Hypertension. Eur. Respir. J. 2019, 53, 1801805. [Google Scholar] [CrossRef]
  33. Kim, N.H.; Lang, I.M. Risk Factors for Chronic Thromboembolic Pulmonary Hypertension. Eur. Respir. Rev. 2012, 21, 27–31. [Google Scholar] [CrossRef]
  34. Frey, M.K.; Alias, S.; Winter, M.P.; Redwan, B.; Stübiger, G.; Panzenboeck, A.; Alimohammadi, A.; Bonderman, D.; Jakowitsch, J.; Bergmeister, H.; et al. Splenectomy Is Modifying the Vascular Remodeling of Thrombosis. J. Am. Heart Assoc. 2014, 3, e000772. [Google Scholar] [CrossRef]
  35. Heresi, G.A.; Mey, J.T.; Bartholomew, J.R.; Haddadin, I.S.; Tonelli, A.R.; Dweik, R.A.; Kirwan, J.P.; Kalhan, S.C. Plasma Metabolomic Profile in Chronic Thromboembolic Pulmonary Hypertension. Pulm. Circ. 2020, 10, 2045894019890553. [Google Scholar] [CrossRef]
  36. Wiest, R.; Krag, A.; Gerbes, A. Spontaneous Bacterial Peritonitis: Recent Guidelines and beyond. Gut 2012, 61, 297–310. [Google Scholar] [CrossRef] [PubMed]
  37. Goh, Z.N.L.; Teo, R.Y.L.; Chung, B.K.; Wong, A.C.; Seak, C.-J. At the Heart of the Problem: Congestive Cardiac Failure as a Cause of Ascites: A Narrative Review. Medicine 2022, 101, e29951. [Google Scholar] [CrossRef] [PubMed]
  38. Farrugia, M.A.; Le Corvec, M.; Renou, C.; Nousbaum, J.-B.; Ouizeman, D.J.; Sire, O.; Loréal, O.; Tariel, H.; Bernard, J.; Piche, T.; et al. Mid-Infrared Spectroscopy as a New Tool for Ruling out Spontaneous Bacterial Peritonitis: A Proof-of-Concept Study. Biomedicines 2023, 11, 838. [Google Scholar] [CrossRef] [PubMed]
  39. Canakis, A.; Canakis, J.; Lohani, M.; Ostrander, T. Spontaneous Bacterial Peritonitis in Cardiac Ascites: A Rare but Deadly Occurrence. Am. J. Case Rep. 2019, 20, 1446–1448. [Google Scholar] [CrossRef]
  40. Farias, A.Q.; Silvestre, O.M.; Garcia-Tsao, G.; da Costa Seguro, L.F.B.; de Campos Mazo, D.F.; Bacal, F.; Andrade, J.L.; Gonçalves, L.L.; Strunz, C.; Ramos, D.S.; et al. Serum B-Type Natriuretic Peptide in the Initial Workup of Patients with New Onset Ascites: A Diagnostic Accuracy Study. Hepatology 2014, 59, 1043–1051. [Google Scholar] [CrossRef]
  41. Trongtorsak, A.; Kittipibul, V.; Antala, D.; Meng, Q.; Puwanant, S. Heart Failure-Related Ascites With Low Serum-Ascites Albumin Gradient: Diagnostic Clues From Triphasic Abdominal Computed Tomography. Cureus 2022, 14, e21251. [Google Scholar] [CrossRef]
  42. Runyon, B.A. AASLD Practice Guidelines Committee Management of Adult Patients with Ascites due to Cirrhosis: An Update. Hepatology 2009, 49, 2087–2107. [Google Scholar] [CrossRef]
  43. Feng, Y.; Yu, Z.; Tang, M.; Li, J.; Peng, B.; Juaiti, M.; Tang, Y.; Liang, B.; Ouyang, M.; Liu, Q.; et al. Transcriptome-Wide N6-Methyladenosine Alternations in Pulmonary Arteries of Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats and Novel Therapeutic Targets. Biomedicines 2024, 12, 364. [Google Scholar] [CrossRef]
  44. Su, H.; Wang, G.; Wu, L.; Ma, X.; Ying, K.; Zhang, R. Transcriptome-Wide Map of m6A circRNAs Identified in a Rat Model of Hypoxia Mediated Pulmonary Hypertension. BMC Genom. 2020, 21, 39. [Google Scholar] [CrossRef] [PubMed]
  45. Hu, L.; Wang, J.; Huang, H.; Yu, Y.; Ding, J.; Yu, Y.; Li, K.; Wei, D.; Ye, Q.; Wang, F.; et al. YTHDF1 Regulates Pulmonary Hypertension through Translational Control of MAGED1. Am. J. Respir. Crit. Care Med. 2021, 203, 1158–1172. [Google Scholar] [CrossRef] [PubMed]
  46. Thenappan, T.; Chan, S.Y.; Weir, E.K. Role of Extracellular Matrix in the Pathogenesis of Pulmonary Arterial Hypertension. Am. J. Physiol. Heart Circ. Physiol. 2018, 315, H1322–H1331. [Google Scholar] [CrossRef]
  47. Shafiq, M.; Jagavelu, K.; Iqbal, H.; Yadav, P.; Chanda, D.; Verma, N.K.; Ghosh, J.K.; Gaestel, M.; Hanif, K. Inhibition of Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 (MK2) Is Protective in Pulmonary Hypertension. Hypertension 2021, 77, 1248–1259. [Google Scholar] [CrossRef] [PubMed]
  48. Zeng, Y.; Huang, T.; Zuo, W.; Wang, D.; Xie, Y.; Wang, X.; Xiao, Z.; Chen, Z.; Liu, Q.; Liu, N.; et al. Integrated Analysis of m6A mRNA Methylation in Rats with Monocrotaline-Induced Pulmonary Arterial Hypertension. Aging 2021, 13, 18238–18256. [Google Scholar] [CrossRef]
  49. Zhang, C.; Zhang, T.; Lu, W.; Duan, X.; Luo, X.; Liu, S.; Chen, Y.; Li, Y.; Chen, J.; Liao, J.; et al. Altered Airway Microbiota Composition in Patients With Pulmonary Hypertension. Hypertension 2020, 76, 1589–1599. [Google Scholar] [CrossRef]
  50. Wang, T.; Xing, Y.; Peng, B.; Yang, K.; Zhang, C.; Chen, Y.; Geng, G.; Li, Q.; Fu, J.; Li, M.; et al. Respiratory Microbiome Profile of Pediatric Pulmonary Hypertension Patients Associated with Congenital Heart Disease. Hypertension 2023, 80, 214–226. [Google Scholar] [CrossRef]
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