Pulmonary arterial hypertension associated with congenital heart disease: An omics study

Zhao, Maolin; Liu, Jian; Xin, Mei; Yang, Ke; Huang, Honghao; Zhang, Wenxin; Zhang, Jinbao; He, Siyi

doi:10.3389/fcvm.2023.1037357

Cited by 2 publications

(1 citation statement)

References 100 publications

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“… 25 Newer genetic mutations have also been identified in cases of pulmonary arterial hypertension including the SRY-related high-mobility-group (HMG) box transcription factor 17 (SOX17). 26 A recent study that looked at 4241 patients with pulmonary arterial hypertension cases from the National Biological Sample and Data Repository for pulmonary hypertension identified other possible genetic mutations including fibulin 2 and platelet-derived growth factor D. 27 These genetic mutations may have roles to play in patients with CHD related pulmonary hypertension. This presupposes that the precapillary pulmonary hypertension that is caused in VSD may not entirely be as a result of the volume overload but also the manifestation of primary pulmonary hypertension as a result of mutations in the above-mentioned genes.…”

Section: Discussionmentioning

confidence: 99%

Severe Pulmonary Hypertension From Combined Ventricular Septal Defect and Rheumatic MIitral Valve Disease: A Case Report and Literature Review

Owusu,

Amponsah,

Wiafe

2024

Clin Med Insights Case Rep

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Most individuals with ventricular septal defect survive to adulthood which allows time for other complications such as pulmonary arterial hypertension to gradually develop over a period of time. When there are other associated cardiac conditions that also contribute to the development of pulmonary hypertension such as valvular heart disease, the pulmonary hypertension may be exaggerated. Because these different etiologies of the pulmonary hypertension have different mechanisms, their coexistence can complicate patient management. We present a 26-year-old man with a large ventricular septal defect and rheumatic mitral valve disease who developed severe pulmonary hypertension that became complicated by atrial fibrillation and later sudden cardiac death.

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Section: Discussionmentioning

confidence: 99%

Severe Pulmonary Hypertension From Combined Ventricular Septal Defect and Rheumatic MIitral Valve Disease: A Case Report and Literature Review

Owusu,

Amponsah,

Wiafe

2024

Clin Med Insights Case Rep

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A multimodal approach identifies lactate as a central feature of right ventricular failure that is detectable in human plasma

Hemnes,

Fortune,

Simon

et al. 2024

Front. Med.

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BackgroundIn PAH metabolic abnormalities in multiple pathways are well-recognized features of right ventricular dysfunction, however, prior work has focused mainly on the use of a single “omic” modality to describe a single deranged pathway. We integrated metabolomic and epigenomic data using transcriptomics in failing and non-failing RVs from a rodent model to provide novel mechanistic insight and translated these findings to accessible human specimens by correlation with plasma from PAH patients.MethodsStudy was conducted in a doxycycline-inducible BMPR2 mutant mouse model of RV failure. Plasma was collected from controls and PAH patients. Transcriptomic and metabolomic analyses were done on mouse RV tissue and human plasma. For mouse RV, we layered metabolomic and transcriptomic data for multiple metabolic pathways and compared our findings with metabolomic and transcriptomic data obtained for human plasma. We confirmed our key findings in cultured cardiomyocyte cells with BMPR2 mutation.ResultsIn failing mouse RVs, (1) in the glycolysis pathway, glucose is converted to lactate via aerobic glycolysis, but may also be utilized for glycogen, fatty acid, and nucleic acid synthesis, (2) in the fatty acid pathway, FAs are accumulated in the cytoplasm because the transfer of FAs to mitochondria is reduced, however, the ß-oxidation pathway is likely to be functional. (3) the TCA cycle is altered at multiple checkpoints and accumulates citrate, and the glutaminolysis pathway is not activated. In PAH patients, plasma metabolic and transcriptomic data indicated that unlike in the failing BMPR2 mutant RV, expression of genes and metabolites measured for the glycolysis pathway, FA pathway, TCA cycle, and glutaminolysis pathway were increased. Lactate was the only metabolite that was increased both in RV and circulation. We confirmed using a stable isotope of lactate that cultured cardiomyocytes with mutant BMPR2 show a modest increase in endogenous lactate, suggesting a possibility of an increase in lactate production by cardiomyocytes in failing BMPR2 mutant RV.ConclusionIn the failing RV with mutant BMPR2, lactate is produced by RV cardiomyocytes and may be secreted out, thereby increasing lactate in circulation. Lactate can potentially serve as a marker of RV dysfunction in PAH, which warrants investigation.

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Pulmonary arterial hypertension associated with congenital heart disease: An omics study

Cited by 2 publications

References 100 publications

Severe Pulmonary Hypertension From Combined Ventricular Septal Defect and Rheumatic MIitral Valve Disease: A Case Report and Literature Review

Severe Pulmonary Hypertension From Combined Ventricular Septal Defect and Rheumatic MIitral Valve Disease: A Case Report and Literature Review

A multimodal approach identifies lactate as a central feature of right ventricular failure that is detectable in human plasma

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