Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a debilitating disease, for which the underlying pathophysiological mechanisms have yet to be fully elucidated. Occurrence of a pulmonary embolism (PE) is a major risk factor for the development of CTEPH, with non-resolution of the thrombus being considered the main cause of CTEPH. Polymorphisms in the α-chain of fibrinogen have been linked to resistance to fibrinolysis in CTEPH patients, and could be responsible for development and disease progression. However, it is likely that additional genetic predisposition, as well as genetic and molecular alterations occurring as a consequence of tissue remodeling in the pulmonary arteries following a persistent PE, also play an important role in CTEPH. This review summarises the current knowledge regarding genetic differences between CTEPH patients and controls (with or without pulmonary hypertension). Mutations in BMPR2, differential gene and microRNA expression, and the transcription factor FoxO1 have been suggested to be involved in the processes underlying the development of CTEPH. While these studies provide the first indications regarding important dysregulated pathways in CTEPH (e.g., TGF-β and PI3K signaling), additional in-depth investigations are required to fully understand the complex processes leading to CTEPH.
Keywords: biomarkers; chronic thromboembolic pulmonary hypertension; genetic alterations; microRNAs; molecular factors; mutations; pathophysiology.