Effects of mechanical ventilation on the interstitial extracellular matrix in healthy lungs and lungs affected by acute respiratory distress syndrome: a narrative review

Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage in the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly in conditions such as acute respiratory distress syndrome (ARDS). This review discusses the detailed structure of the ECM in healthy and ARDS-affected lungs under mechanical ventilation, aiming to bridge the gap between experimental insights and clinical practice by offering a thorough understanding of lung ECM organization and the dynamics of its alteration during mechanical ventilation. Focusing on the clinical implications, we explore the potential of precise interventions targeting the ECM and cellular signaling pathways to mitigate lung damage, reduce inflammation, and ultimately improve outcomes for critically ill patients. By analyzing a range of experimental studies and clinical papers, particular attention is paid to the roles of matrix metalloproteinases (MMPs), integrins, and other molecules in ECM damage and VILI. This synthesis not only sheds light on the structural changes induced by mechanical stress but also underscores the importance of cellular responses such as inflammation, fibrosis, and excessive activation of MMPs. This review emphasizes the significance of mechanical cues transduced by integrins and their impact on cellular behavior during ventilation, offering insights into the complex interactions between mechanical ventilation, ECM damage, and cellular signaling. By understanding these mechanisms, healthcare professionals in critical care can anticipate the consequences of mechanical ventilation and use targeted strategies to prevent or minimize ECM damage, ultimately leading to better patient management and outcomes in critical care settings. Question: How does mechanical ventilation affect the lung’s interstitial extracellular matrix (ECM), with a specific focus on ECM organization in healthy lungs and those affected by acute respiratory distress syndrome (ARDS). Findings: The narrative review reveals that mechanical ventilation induces stress on the interstitial ECM, leading to inflammation, fibrogenesis, elastogenesis, and matrix metalloproteinase hyperactivity. Matrix metalloproteinase and integrin involvement in ECM damage are emphasized. Our findings are based on a narrative review of studies of mechanical ventilation-induced alterations of interstitial ECM organization and cellular response. Meaning: The key conclusion is that understanding the intricate processes of interstitial ECM damage, as well as cell signaling and communication related to ventilation-induced lung injury, can pave the way for more targeted interventions that have the potential to mitigate lung damage and improve outcomes for patients in critical care settings.