Molecular and pathophysiological intersections between arterial hypertension, pulmonary inflammation and diabetes...

The pathophysiological interactions between arterial hypertension (AH), pulmonary inflammation (PI) and diabetes mellitus (DM) have been widely studied due to their clinical relevance and global impact. Chronic inflammation and oxidative stress act as central axes that exacerbate these conditions, creating a pro-inflammatory and harmful environment. This study aims at characterizing the immunological and molecular mechanisms shared by these pathologies, highlighting the signaling pathways that connect these conditions and their implications for therapeutic management. The scoping review followed JBI and PRISMA-ScR guidelines. Descriptors such as "Hypertension", "Pulmonary inflammation" and "Diabetes" were used, and then 48 articles were selected. Data extracted included inflammatory markers, molecular mediators and pathogenic mechanisms. The methodology ensured the consistency of the analysis and relevance of the findings of articles published in the last 10 years. The results indicated that arterial hypertension aggravated pulmonary inflammation by systemic inflammatory responses, promoted the activation of NF-κB and increased pro-inflammatory cytokines, such as TNF-α, compromising pulmonary vascular integrity and favoring tissue remodeling. Simultaneously, chronic hyperglycemia in diabetes mellitus intensifies these processes by inducing oxidative stress and endothelial dysfunction, reducing the bioavailability of nitric oxide (NO). These effects are possibly potentiated by the activation of the renin-angiotensin-aldosterone system and the mineralocorticoid receptor, promoting vasoconstriction and inflammation. Hyperglycemia stimulates the production of reactive oxygen species (ROS) and activates NF-κB, leading to the release of TNF-α and IL-6, perpetuating vascular dysfunction. Furthermore, macrophage- and neutrophil-mediated IP contributes to pulmonary vascular remodeling and impaired gas exchange, aggravating hypertension and DM. Interventions such as SGLT2 inhibitors have demonstrated potential to modulate the three affected systems, while biomarkers such as NF-κB and TNF-α emerge as promising targets for integrated strategies, since they are considered key modulators of the conditions under study. Indeed the intersection between these conditions could be mediated by shared pathways, as mentioned above, which maintain systemic and local inflammation. These markers play crucial roles in the progression of the analyzed conditions, highlighting the need for integrated therapeutic strategies modulating inflammation, oxidative stress, and vascular remodeling. Those approaches may mitigate the interdependent impacts of these diseases and offer new avenues for personalized treatments.