Abstract
Aims: The development of neuroinflammation deteriorates the prognosis of myocardial infarction (MI). We aimed to investigate the effect of renal denervation (RDN) on post-MI neuroinflammation in rats and the related mechanisms.Methods and Results: Male adult Sprague-Dawley rats were subjected to sham or ligation of the left anterior descending coronary artery to induce MI. One week later, the MI rats received a sham or RDN procedure. Their cardiac functions were analyzed by echocardiography, and their intestinal structures, permeability, and inflammatory cytokines were tested. The intestinal microbiota were characterized by 16S rDNA sequencing. The degrees of neuroinflammation in the brains of rats were analyzed for microglia activation, inflammatory cytokines, and inflammation-related signal pathways. In comparison with the Control rats, the MI rats exhibited impaired cardiac functions, intestinal injury, increased intestinal barrier permeability, and microbial dysbiosis, accompanied by increased microglia activation and pro-inflammatory cytokine levels in the brain. A RDN procedure dramatically decreased the levels of renal and intestinal sympathetic nerve activity, improved cardiac functions, and mitigated the MI-related intestinal injury and neuroinflammation in the brain of MI rats. Interestingly, the RDN procedure mitigated the MI-increased intestinal barrier permeability and pro-inflammatory cytokines and plasma LPS as well as ameliorated the gut microbial dysbiosis in MI rats. The protective effect of RDN was not significantly affected by treatment with intestinal alkaline phosphatase but significantly reduced by L-phenylalanine treatment in MI rats.Conclusions: RDN attenuated the neuroinflammation in the brain of MI rats, associated with mitigating the MI-related intestinal injury.
Highlights
Myocardial infarction (MI) is one of the most dangerous diseases that threaten public health
Echocardiography showed that MI increased left ventricular end-systolic diameter (LVDs) and left ventricular end-diastolic diameter (LVDd), decreased left ventricular anterior wall diastolic thickness (LVAWd), as well as reduced ejection fraction
Echocardiography revealed that there was no significant difference in the cardiac functional measures between the MI and Renal denervation (RDN) groups before RDN procedure (Supplementary Figure 1)
Summary
Myocardial infarction (MI) is one of the most dangerous diseases that threaten public health. Emergency revascularization of the coronary artery has been widely applied, long-term complications, for long-term cognitive impairment post MI, remain a big challenge [1]. There is still no specific treatment for improving cognitive impairment in MI. A recent study has pointed that neuroinflammation is crucial for the development of cognitive deterioration [2]. Neuroinflammation can occur in the early stage of functional impairment in the central nervous system (CNS) [3] and have been observed in both MI mice and coronary heart disease (CHD) patients [4].
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