Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension

Abstract

Hypoxic pulmonary hypertension (HPH) is a complicated vascular disorder characterized by diverse mechanisms that lead to elevated blood pressure in pulmonary circulation. Recent evidence indicates that HPH is not simply a pathological syndrome but is instead a complex lesion of cellular metabolism, inflammation, and proliferation driven by the reprogramming of gene expression patterns. One of the key mechanisms underlying HPH is hypoxia, which drives immune/inflammation to mediate complex vascular homeostasis that collaboratively controls vascular remodeling in the lungs. This is caused by the prolonged infiltration of immune cells and an increase in several pro-inflammatory factors, which ultimately leads to immune dysregulation. Hypoxia has been associated with metabolic reprogramming, immunological dysregulation, and adverse pulmonary vascular remodeling in preclinical studies. Many animal models have been developed to mimic HPH; however, many of them do not accurately represent the human disease state and may not be suitable for testing new therapeutic strategies. The scientific understanding of HPH is rapidly evolving, and recent efforts have focused on understanding the complex interplay among hypoxia, inflammation, and cellular metabolism in the development of this disease. Through continued research and the development of more sophisticated animal models, it is hoped that we will be able to gain a deeper understanding of the underlying mechanisms of HPH and implement more effective therapies for this debilitating disease.

The role of immune cells and inflammation in pulmonary hypertension: mechanisms and implications

“…This may be because the increase of CCL2 produced by pulmonary vascular cells contributes to the increase of chemotactic activity of monocytes/macrophages. So that adventitial fibroblasts are activated ( 69 , 70 ), the migration and proliferation of PASMCs increased, and pathological vascular remodeling was induced. In the presence of pulmonary ECs, the mobility of monocytes decreased significantly, while the blocking antibody of CCL2 increased significantly.…”

Single cell transcriptomic analyses reveal diverse and dynamic changes of distinct populations of lung interstitial macrophages in hypoxia-induced pulmonary hypertension

“…In PH, hypoxia and immune dysfunction are central contributors to disease pathogenesis (5)(6)(7)(8)(9)(10). The mechanisms through which hypoxia and immune dysfunction contribute to PH have been examined in animal models, including hypoxia-induced PH (11,12). Myeloid leukocytes, especially macrophages, are thought to be the primary effectors of inflammation and remodeling in the PH vessel wall (1,5).…”