PI3K Inhibitors as Potential Therapeutic Agents for the Treatment of COPD with Associated Atherosclerosis

Abstract

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) share a complex and multifactorial relationship characterized by overlapping risk factors, systemic inflammation, and intertwined pathophysiological mechanisms, with atherosclerosis emerging as a central inflammatory process connecting COPD and CVD, driven by systemic inflammation, oxidative stress, and endothelial dysfunction. While systemic inflammation is recognized as a critical link between these conditions, the precise pathways through which inflammation arises remain under investigation. There is therefore a need for therapeutic strategies to mitigate cardiovascular risks in patients with COPD. Among the pathways contributing to this interplay, the phosphoinositide 3-kinase (PI3K) signaling pathway has gained significant attention. Dysregulated PI3K signaling contributes to inflammation, oxidative stress, and endothelial dysfunction, which are key drivers of both COPD and CVD. Consequently, PI3K inhibitors have emerged as a promising therapeutic approach to mitigate inflammation and oxidative damage, offering a targeted strategy to address the shared pathological mechanisms underlying these diseases. A comprehensive understanding of the role of PI3K signaling and its inhibitors could facilitate the development of novel interventions to reduce cardiovascular risk in patients with COPD.

Fig. 1

Summary of the expression and roles of PI3K isoforms in cardiac and lung function. Each bar corresponds to an isoform, with detailed annotations for its expression pattern and role in cardiac or lung function and pathology