Abstract
Cardiovascular disease (CVD), including myocardial infarction (MI and heart attack), is a leading cause of death in Aotearoa New Zealand and globally. Patients who survive an MI are at much greater risk of future cardiovascular events, such as heart failure. Preliminary data from the Christchurch Heart Institute (CHI) has shown that patients post-MI have a higher amount of circulating bacterial DNA, from Klebsiella pneumoniae, in their blood. Increased bacterial DNA in the bloodstream has been associated with intestinal barrier dysfunction. An intact intestinal barrier limits the translocation of microbes from the gut; however, when the barrier is breached this leads to translocation of microbes and microbial components into the circulatory system. Bacterial components such as lipopolysaccharides (LPS) interact with immune cells in the blood and induce an inflammatory response. This study aimed to investigate the relationship between circulating bacterial LPS and systemic inflammation in patients after an MI. First, LPS binding protein (LBP) was used as a surrogate marker for LPS to investigate whether increased intestinal permeability is observed in patients that have had an MI. LPS derived from Klebsiella pneumoniae was then investigated to determine whether it would increase the production of inflammatory immune markers in healthy peripheral blood cells.
The concentration of LBP was measured using an ELISA, and preliminary validation was performed prior to testing patient samples. Patients who have had an MI and subsequently developed heart failure, had a significantly higher concentration of LBP, compared to patients who had an MI and did not go on to have heart failure, compared to healthy controls and compared to non-cardiac chest pain controls. This suggests patients who have had an MI that subsequently developed heart failure are likely to have increased intestinal permeability. Gut bacteria in the blood may also have the potential to induce inflammation and increase the risk of future cardiovascular events after an MI.
Measurement of immune marker expression in peripheral blood cells, following stimulation by K. pneumoniae LPS was performed using a LEGENDplex assay and flow cytometry. However, due to technical complications, analysis of immune marker expression was limited.
This study demonstrated that the patients who have had an MI have a higher concentration of LBP compared to controls, suggesting a potential contribution of gut-derived LPS in post-MI inflammation. These results establish the groundwork for future research into the role of bacterial LPS in the development of heart failure after an MI.