High-altitude pulmonary hypertension: a comprehensive review of mechanisms and management

Abstract

High-altitude pulmonary hypertension (HAPH) is characterized by an increase in pulmonary artery pressure due to prolonged exposure to hypoxic environment at high altitudes. The development of HAPH involves various factors such as pressure changes, inflammation, oxidative stress, gene regulation, and signal transduction. The pathophysiological mechanisms of this condition operate at molecular, cellular, and genetic levels. Diagnosis of HAPH often relies on echocardiography, cardiac catheterization, and other methods to assess pulmonary artery pressure and its impact on cardiac function. Treatment options for HAPH encompass both nondrug and drug therapies. While advancements have been made in understanding the pathological mechanisms through research on animal models and clinical trials, there are still limitations to be addressed. Future research should focus on exploring molecular targets, personalized medicine, long-term management strategies, and interdisciplinary approaches. By leveraging advanced technologies like systems biology, omics technology, big data, and artificial intelligence, a comprehensive analysis of HAPH pathogenesis can lead to the identification of new treatment targets and strategies, ultimately enhancing patient quality of life and prognosis. Furthermore, research on health monitoring and preventive measures for populations living at high altitudes should be intensified to reduce the incidence and mortality of HAPH.

Keywords: Diagnosis; High-altitude pulmonary hypertension; Hypoxic environment; Pathogenesis; Treatment strategies.

Fig. 1

Pathogenesis of high-altitude pulmonary hypertension

Fig. 2

HIF signaling pathway under hypoxic/normoxic conditions [40]. Under normoxia, the stability and activity of HIF-1α and HIF-2α are low as they are hydroxylated by oxygen-dependent proteolytic enzymes, recognized by the VHL protein complex, and degraded through ubiquitination [41]. In hypoxic conditions, inhibition of prolyl hydroxylase (PHD) activity leads to increased stability of HIF-1α and HIF-2α. The stabilized HIF-α subunit forms a complex with HIF-1β, translocates to the nucleus, and binds to the HIF response element, activating the transcription of downstream genes [42]