Temporal effects of LPS-induced inflammation on aortic remodelling and function

BACKGROUND: Inflammation-induced vascular remodelling and dysfunction are key contributors to the development of cardiovascular disease; however, vessel remodelling processes may vary depending on the inflammatory stimulus. This study explored how varying durations of systemic inflammation impact the molecular pathways underlying aortic remodelling. METHODS: Sprague-Dawley rats were assigned to 24-h (24H), one-week (1 W), and four-week (4 W) groups, each subdivided into control or lipopolysaccharide (LPS)-treated groups. The 24H and 1 W groups received a single injection of saline or LPS and were terminated after 24H and 1 W, respectively. The 4 W group received single, weekly injections of saline or LPS for four weeks and was terminated seven days after the final dose. We measured blood pressure (BP); aortic function (echo-tracking); circulating cytokine concentrations (ELISA); mRNA expression (RT-PCR); structural remodelling (histology); and lipidomic alterations (AP-MALDI MSI). RESULTS: Circulating cytokines were increased in all LPS groups. Inflammatory, endothelial activation, and arterial remodelling genes were upregulated within 24 h of acute inflammation, without altering BP or aortic function. After one week, matrix metalloproteinase-9 expression and structural remodelling were elevated, while aortic compliance was decreased. With repeated LPS exposure, chronic inflammatory signalling markers were increased, alongside increased systolic BP, structural and metabolic remodelling, and aortic stiffness parameters. CONCLUSION: Inflammation differentially and temporally affects the aorta. Early immune activation upregulates genes involved in inflammation and aortic remodelling without immediate dysfunction. In contrast, chronic inflammation upregulates genes associated with long-term NF-κB activation which impacts aortic functional changes, likely through increases in structural remodelling and aortic stiffness.