Causes of Pulmonary Hypertension

Author: Shelley Ensz. Scleroderma is highly variable. See Types of Scleroderma. Read Disclaimer
Altitude and Hypoxia
Antiphospholipid Antibodies
Endothelial Dysfunction
Estrogen and Enzyme CYP1B1
Vascular Disease/Scleroderma


There are dozens of causes of pulmonary hypertension, ranging from genetics, medications or street drugs, connective tissue diseases (such as scleroderma), heart and lung diseases, and blood disorders.

Causes of Pulmonary Hypertension. Depending on the type, pulmonary hypertension can have many potential causes. MayoClinic.

Altitude and Hypoxia

Effects of Iron Supplementation and Depletion on Hypoxic Pulmonary Hypertension Two Randomized Controlled Trials. Hypoxia is a major cause of pulmonary hypertension in respiratory disease and at high altitude. Hypoxic pulmonary hypertension may be attenuated by iron supplementation and exacerbated by iron depletion. Thomas G. Smith, MBBS, DPhil. JAMA. 2009;302(13):1444-1450. (Also see Hypoxia, and Vitamins/Minerals)

Antiphospholipid Antibodies (APLA)

The association of antiphospholipid antibodies (APLA) with cardiopulmonary manifestations of systemic sclerosis. APLA is associated with pulmonary arterial hypertension (PH), interstitial lung disease, Raynaud's phenomenon and digital ulcers, so endothelial abnormalities and small vessel thrombosis may be important in the pathogenesis of these disease features. PubMed, Clin Exp Rheumatol, 2014 Feb 24. (Also see Antiphospholipid Syndrome, Raynaud's and Digital Ulcers)

Endothelial Dysfunction

Endothelin and Systemic Scleroderma. Endothelin is a protein that helps to regulate contraction and relaxation of the smooth muscle found in the walls of blood vessels and internal organs (except the heart). An overproduction of endothelin, whether by illness or medication, can cause blood vessels to constrict and blood pressure to increase. In scleroderma, it can cause pulmonary arterial hypertension (PAH). ISN.

Endothelin and Systemic Scleroderma Endothelin Receptor Antagonists

Estrogen and Enzyme CYP1B1

The serotonin transporter (SERT) promotes a pathological estrogen metabolic pathway in pulmonary hypertension (PAH) via cytochrome P450 1B1. Increased intracellular serotonin caused by increased SERT expression may contribute to PAH pathobiology by dysregulation of estrogen metabolic pathways via increased CYP1B1 activity. PubMed, Pulm Circ, 2016 Mar;6(1):82-92.


Elevated Adipsin Levels are Associated with Pulmonary Arterial Hypertension (PAH) in Systemic Sclerosis (SSC). Mechanistically, adipsin might represent a pathogenic link between adipocyte dysfunction and complement pathway activation, and play an important role in the pathogenesis of SSc–PAH. PubMed, Arthritis Rheumatol, 06/26/2017.

Inflammation and Pulmonary Hypertension (PH). Evidence is accumulating to suggest that inflammation plays a significant role in the pathogenesis of PH. Endothelial cells play an important role in inflammation and immune reactions, and inflammatory cytokines cause endothelial dysfunction. Cardiology in Review. March/April 2010.

Medications that Cause Pulmonary Hypertension

Dasatinib Could Increase Risk for Pulmonary Hypertension. The FDA has warned that dasatinib (Sprycel, Bristol-Myers Squibb) may increase the risk for pulmonary arterial hypertension (PAH). Dasatinib is used to treat certain types of leukemia, and is sometimes used off-label for other cancers.

Vascular Disease and Scleroderma

Vascular Disease and Systemic Scleroderma. The vascular system is our circulatory system. It consists of all the vessels that carry blood and lymph through the body, to and from organs. Vessels include arteries, veins, and capillaries. Any condition that affects the vascular system, all of in part, is considered a vascular disease. ISN.

Vascular in Scleroderma
Types in Scleroderma
In Other CTDs
Personal Stories
Related Information
Go to Pulmonary Hypertension Diagnosis

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