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Pulmonary_hypertension

Cardiovascular Disorder MONDO:0005149 Heart Disease Lung Disease
0
Mappings
0
Definitions
0
Inheritance
7
Pathophysiology
0
Histopathology
8
Phenotypes
9
Genes
5
Treatments
2
Subtypes
0
Differentials
0
Datasets
0
Trials
◆

Subtypes

2
Pulmonary Arterial Hypertension (PAH) Not Yet Curated MONDO:0015924
A type of pulmonary hypertension characterized by high blood pressure in the arteries that supply the lungs, often idiopathic or associated with other conditions.
Secondary Pulmonary Hypertension
Pulmonary hypertension that occurs as a result of other diseases such as left heart disease, chronic lung disease, or thromboembolic disease.
⚙

Pathophysiology

7
Vascular Remodeling
Structural changes in the pulmonary vasculature including smooth muscle hypertrophy, intimal proliferation, and fibrosis.
Smooth Muscle Cell link Endothelial Cell link fibroblast link pericyte link
extracellular matrix organization link smooth muscle cell proliferation link
pulmonary artery link
Endothelial Dysfunction
Endothelial injury and apoptosis with loss of BMPR2/BMP protective signaling; endothelial-to-mesenchymal transition contributing to vascular remodeling.
Endothelial Cell link
endothelial to mesenchymal transition link apoptotic process link BMP signaling pathway link
pulmonary artery link
Inflammation and Immune Activation
Perivascular immune cell infiltration and cytokine release fueling proliferative and fibrotic processes.
macrophage link
inflammatory response link NF-kappaB signaling link
pulmonary artery link
Metabolic Reprogramming
Shift from oxidative phosphorylation to glycolysis in vascular cells, supporting proliferation and apoptosis resistance.
Smooth Muscle Cell link Endothelial Cell link
glycolytic process link oxidative phosphorylation link
Hypoxia Signaling
Hypoxia-inducible factor (HIF) pathway activation contributing to vasoconstriction and vascular remodeling.
response to hypoxia link HIF-1-alpha signaling pathway link
Increased Pulmonary Vascular Resistance
Result of vascular remodeling and vasoconstriction leading to elevated pressure in the pulmonary artery.
pulmonary artery link
Right Ventricular Hypertrophy
The right ventricle thickens in response to increased workload from elevated pulmonary arterial pressure.
right cardiac ventricle link
⬡

Causal Graph

Referential integrity issues (1):
  • Target 'Right Heart Failure' (from 'Right Ventricular Hypertrophy') not found in named elements
graph LR
    Right_Heart_Failure["Right Heart Failure"]
    Reduced_Exercise_Tolerance["Reduced Exercise Tolerance"]
    Right_Ventricular_Hypertrophy["Right Ventricular Hypertrophy"]
    Dyspnea["Dyspnea"]

    Right_Ventricular_Hypertrophy -.-> Right_Heart_Failure
    Dyspnea --> Reduced_Exercise_Tolerance

    style Right_Heart_Failure fill:#fee2e2,stroke:#dc2626,stroke-dasharray: 5 5
    style Reduced_Exercise_Tolerance fill:#fef3c7
    style Right_Ventricular_Hypertrophy fill:#dbeafe
    style Dyspnea fill:#fef3c7
●

Phenotypes

8
Cardiovascular(2) Integument(1) Metabolism(1) Respiratory(1) Constitutional(3)
Cardiovascular 2
Syncope FREQUENT Syncope (HP:0001279)
Fainting spells associated with exertion.
Palpitations FREQUENT Palpitations (HP:0001962)
Integument 1
Cyanosis OCCASIONAL Cyanosis (HP:0000961)
Bluish discoloration due to inadequate oxygenation
Metabolism 1
Edema OCCASIONAL Edema (HP:0000969)
Swelling in the legs and ankles
Respiratory 1
Dyspnea VERY_FREQUENT Dyspnea (HP:0002094)
Sequelae: Reduced Exercise Tolerance
Constitutional 3
Chest Pain FREQUENT Chest pain (HP:0100749)
Fatigue FREQUENT Fatigue (HP:0012378)
Due to reduced cardiac output
Reduced Exercise Tolerance FREQUENT Exercise intolerance (HP:0003546)
🧬

Genetic Associations

9
BMPR2 (Loss-of-function variants central in heritable and idiopathic PAH)
SMAD9 (TGF-beta/BMP axis component implicated in PAH)
ACVRL1 (Implicated in PAH, particularly in hereditary hemorrhagic telangiectasia-associated PAH)
ENG (Implicated in PAH)
EIF2AK4 (Causally linked to pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH))
KCNK3 (Ion channel mutations contribute to vasoconstriction and proliferation)
TBX4 (Transcriptional regulator contributing to developmental and adult-onset PAH)
SOX17 (Variants associated with severe PAH phenotype)
CAV1 (Implicated in vascular dysfunction)
💊

Treatments

5
Phosphodiesterase-5 Inhibitors MAXO:0000058
Medications like sildenafil and tadalafil that relax blood vessels in the lungs
Endothelin Receptor Antagonists MAXO:0000058
Medications that block the effects of endothelin and help decrease blood pressure in the lungs
Prostacyclin Analogues MAXO:0000058
Medications that mimic the effects of prostacyclin, dilating pulmonary and systemic arterial vascular beds
Oxygen Therapy MAXO:0000503
Used to reduce symptoms in patients with hypoxemia
Anticoagulation MAXO:0000181
Used particularly in chronic thromboembolic pulmonary hypertension to prevent clotting complications
🌍

Environmental Factors

1
High-Altitude Exposure
🔬

Biochemical Markers

1
N-terminal pro b-type Natriuretic Peptide (NT-proBNP) (Elevated)
{ }

Source YAML

click to show 
name: Pulmonary_hypertension
creation_date: '2025-12-04T16:57:31Z'
updated_date: '2026-02-17T21:53:14Z'
category: Cardiovascular Disorder
parents:
- Heart Disease
- Lung Disease
has_subtypes:
- name: Pulmonary Arterial Hypertension (PAH)
  subtype_term:
    preferred_term: pulmonary arterial hypertension
    term:
      id: MONDO:0015924
      label: pulmonary arterial hypertension
  description: A type of pulmonary hypertension characterized by high blood
    pressure in the arteries that supply the lungs, often idiopathic or
    associated with other conditions.
- name: Secondary Pulmonary Hypertension
  description: Pulmonary hypertension that occurs as a result of other diseases
    such as left heart disease, chronic lung disease, or thromboembolic disease.
  review_notes: >-
    MONDO does not have a single term for "secondary pulmonary hypertension" as it
    is
    a clinical classification. Specific secondary causes have individual terms:
    MONDO:0013024 (chronic thromboembolic), MONDO:0017157 (due to lung disease/hypoxia).
prevalence:
- population: Global
  percentage: Rare
progression:
- phase: Onset
  age_range: Variable, can occur at any age
  notes: Presentation depends on underlying cause
genetic:
- name: BMPR2
  association: Loss-of-function variants central in heritable and idiopathic PAH
  notes: BMPR2 encodes bone morphogenetic protein receptor type 2; impaired
    BMP/SMAD1/5/9 signaling is a core mechanism in PAH pathogenesis
- name: SMAD9
  association: TGF-beta/BMP axis component implicated in PAH
  notes: Downstream transcription factor in BMP signaling pathway
- name: ACVRL1
  association: Implicated in PAH, particularly in hereditary hemorrhagic
    telangiectasia-associated PAH
  notes: Also known as ALK1; encodes activin receptor-like kinase 1, involved in
    TGF-beta/BMP signaling
- name: ENG
  association: Implicated in PAH
  notes: Encodes endoglin, a TGF-beta co-receptor involved in vascular
    development
- name: EIF2AK4
  association: Causally linked to pulmonary veno-occlusive disease (PVOD) and
    pulmonary capillary hemangiomatosis (PCH)
  notes: Also known as GCN2; encodes eukaryotic translation initiation factor 2
    alpha kinase 4
- name: KCNK3
  association: Ion channel mutations contribute to vasoconstriction and
    proliferation
  notes: Also known as TASK-1; encodes potassium two pore domain channel
    subfamily K member 3
- name: TBX4
  association: Transcriptional regulator contributing to developmental and
    adult-onset PAH
  notes: Encodes T-box transcription factor 4
- name: SOX17
  association: Variants associated with severe PAH phenotype
  notes: Encodes SRY-box transcription factor 17; regulates vascular development
- name: CAV1
  association: Implicated in vascular dysfunction
  notes: Encodes caveolin-1, involved in caveolae formation and endothelial
    signaling
pathophysiology:
- name: Vascular Remodeling
  description: Structural changes in the pulmonary vasculature including smooth
    muscle hypertrophy, intimal proliferation, and fibrosis.
  cell_types:
  - preferred_term: Smooth Muscle Cell
    term:
      id: CL:0000192
      label: smooth muscle cell
  - preferred_term: Endothelial Cell
    term:
      id: CL:0000115
      label: endothelial cell
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  - preferred_term: pericyte
    term:
      id: CL:0000669
      label: pericyte
  locations:
  - preferred_term: pulmonary artery
    term:
      id: UBERON:0002012
      label: pulmonary artery
  biological_processes:
  - preferred_term: extracellular matrix organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
  - preferred_term: smooth muscle cell proliferation
    term:
      id: GO:0048661
      label: positive regulation of smooth muscle cell proliferation
- name: Endothelial Dysfunction
  description: Endothelial injury and apoptosis with loss of BMPR2/BMP
    protective signaling; endothelial-to-mesenchymal transition contributing to
    vascular remodeling.
  cell_types:
  - preferred_term: Endothelial Cell
    term:
      id: CL:0000115
      label: endothelial cell
  locations:
  - preferred_term: pulmonary artery
    term:
      id: UBERON:0002012
      label: pulmonary artery
  biological_processes:
  - preferred_term: endothelial to mesenchymal transition
    term:
      id: GO:0001837
      label: epithelial to mesenchymal transition
  - preferred_term: apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
  - preferred_term: BMP signaling pathway
    term:
      id: GO:0030509
      label: BMP signaling pathway
- name: Inflammation and Immune Activation
  description: Perivascular immune cell infiltration and cytokine release
    fueling proliferative and fibrotic processes.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  locations:
  - preferred_term: pulmonary artery
    term:
      id: UBERON:0002012
      label: pulmonary artery
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: NF-kappaB signaling
    term:
      id: GO:0038061
      label: NIK/NF-kappaB signaling
- name: Metabolic Reprogramming
  description: Shift from oxidative phosphorylation to glycolysis in vascular
    cells, supporting proliferation and apoptosis resistance.
  cell_types:
  - preferred_term: Smooth Muscle Cell
    term:
      id: CL:0000192
      label: smooth muscle cell
  - preferred_term: Endothelial Cell
    term:
      id: CL:0000115
      label: endothelial cell
  biological_processes:
  - preferred_term: glycolytic process
    term:
      id: GO:0006096
      label: glycolytic process
  - preferred_term: oxidative phosphorylation
    term:
      id: GO:0006119
      label: oxidative phosphorylation
- name: Hypoxia Signaling
  description: Hypoxia-inducible factor (HIF) pathway activation contributing to
    vasoconstriction and vascular remodeling.
  biological_processes:
  - preferred_term: response to hypoxia
    term:
      id: GO:0001666
      label: response to hypoxia
  - preferred_term: HIF-1-alpha signaling pathway
    term:
      id: GO:0097411
      label: hypoxia-inducible factor-1alpha signaling pathway
- name: Increased Pulmonary Vascular Resistance
  description: Result of vascular remodeling and vasoconstriction leading to
    elevated pressure in the pulmonary artery.
  locations:
  - preferred_term: pulmonary artery
    term:
      id: UBERON:0002012
      label: pulmonary artery
- name: Right Ventricular Hypertrophy
  description: The right ventricle thickens in response to increased workload
    from elevated pulmonary arterial pressure.
  locations:
  - preferred_term: right cardiac ventricle
    term:
      id: UBERON:0002080
      label: right cardiac ventricle
  consequences:
  - Right Heart Failure
  downstream:
  - target: Right Heart Failure
    description: Sustained pulmonary hypertension causes right ventricular
      remodeling and eventual right heart failure.
    evidence:
    - reference: PMID:39581144
      supports: SUPPORT
      snippet: Pulmonary arterial hypertension (PAH) is a severe cardiovascular
        disease characterized by elevated pulmonary vascular resistance,
        progressive increases in pulmonary artery pressures, ultimately leading
        to right-sided heart failure
      explanation: This 2024 paper establishes that progressive vascular
        remodeling in PAH leads to increased resistance and right ventricular
        failure.
phenotypes:
- category: Respiratory
  name: Dyspnea
  frequency: VERY_FREQUENT
  diagnostic: true
  sequelae:
  - target: Reduced Exercise Tolerance
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
- category: Cardiovascular
  name: Chest Pain
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Chest pain
    term:
      id: HP:0100749
      label: Chest pain
- category: Cardiovascular
  name: Syncope
  frequency: FREQUENT
  notes: Fainting spells associated with exertion.
  phenotype_term:
    preferred_term: Syncope
    term:
      id: HP:0001279
      label: Syncope
- category: Cardiovascular
  frequency: FREQUENT
  name: Palpitations
  phenotype_term:
    preferred_term: Palpitations
    term:
      id: HP:0001962
      label: Palpitations
- category: Systemic
  frequency: FREQUENT
  name: Fatigue
  notes: Due to reduced cardiac output
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
- category: Cardiovascular
  frequency: OCCASIONAL
  name: Edema
  notes: Swelling in the legs and ankles
  phenotype_term:
    preferred_term: Edema
    term:
      id: HP:0000969
      label: Edema
- category: Cardiovascular
  name: Reduced Exercise Tolerance
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Reduced Exercise Tolerance
    term:
      id: HP:0003546
      label: Exercise intolerance
- category: Respiratory
  name: Cyanosis
  frequency: OCCASIONAL
  notes: Bluish discoloration due to inadequate oxygenation
  phenotype_term:
    preferred_term: Cyanosis
    term:
      id: HP:0000961
      label: Cyanosis
biochemical:
- name: N-terminal pro b-type Natriuretic Peptide (NT-proBNP)
  biomarker_term:
    preferred_term: NT-proBNP
    term:
      id: NCIT:C88524
      label: N-Terminal Fragment Brain Natriuretic Protein
  presence: Elevated
  notes: Indicator of right ventricular strain
diagnosis:
- name: Echocardiogram
  diagnosis_term:
    preferred_term: echocardiography
    term:
      id: MAXO:0010203
      label: echocardiography
  notes: Estimates pulmonary artery pressure and evaluates right heart function
- name: Right Heart Catheterization
  diagnosis_term:
    preferred_term: right heart catheterization
    term:
      id: MAXO:0035118
      label: cardiac catheterization
    located_in:
      preferred_term: right cardiac chamber
      term:
        id: UBERON:0035554
        label: right cardiac chamber
  notes: Definitive test to measure pulmonary artery pressures and confirm
    diagnosis
environmental:
- name: High-Altitude Exposure
  effect: Can exacerbate or trigger symptoms
  environment_context:
    preferred_term: Mountain environment
    term:
      id: ENVO:00000081
      label: mountain
treatments:
- name: Phosphodiesterase-5 Inhibitors
  description: Medications like sildenafil and tadalafil that relax blood
    vessels in the lungs
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
- name: Endothelin Receptor Antagonists
  description: Medications that block the effects of endothelin and help
    decrease blood pressure in the lungs
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
- name: Prostacyclin Analogues
  description: Medications that mimic the effects of prostacyclin, dilating
    pulmonary and systemic arterial vascular beds
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
- name: Oxygen Therapy
  description: Used to reduce symptoms in patients with hypoxemia
  treatment_term:
    preferred_term: artificial respiration
    term:
      id: MAXO:0000503
      label: artificial respiration
- name: Anticoagulation
  description: Used particularly in chronic thromboembolic pulmonary
    hypertension to prevent clotting complications
  treatment_term:
    preferred_term: cardiovascular agent therapy
    term:
      id: MAXO:0000181
      label: cardiovascular agent therapy
review_notes: Pulmonary hypertension is a complex condition characterized by
  elevated blood pressure in the pulmonary arteries, leading to right heart
  strain and failure over time. Symptoms are diverse, with dyspnea, fatigue, and
  chest pain being common presentations. Diagnosis typically involves imaging
  and hemodynamic assessments, while treatment focuses on reducing pulmonary
  pressures and improving symptoms.
disease_term:
  preferred_term: pulmonary hypertension
  term:
    id: MONDO:0005149
    label: pulmonary hypertension
references:
- reference: DOI:10.1038/s41392-025-02287-8
  title: Signaling pathways and targeted therapy for pulmonary hypertension
  findings: []
- reference: DOI:10.1038/s41598-024-64251-w
  title: Transcriptomic profiling highlights cell proliferation in the
    progression of experimental pulmonary hypertension in rats
  findings: []
- reference: DOI:10.1164/rccm.202302-0327so
  title: 'Pulmonary Hypertension: A Contemporary Review'
  findings: []
- reference: DOI:10.31083/j.rcm2506217
  title: Roles of LncRNAs in the Pathogenesis of Pulmonary Hypertension
  findings: []