Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the industrialized world. The gut microbiome influences CVD, through atherogenic metabolites like trimethylamine N-oxide (TMAO) or protective effects through short-chain fatty acids (SCFA) production. The specific alterations in the gut microbiome and downstream metabolites in acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) remain unclear. We enrolled ACS patients within 24 h of clinical presentation with a follow-up of 28 days, using CCS patients as controls. Gut microbiome composition, downstream metabolites, and cardiovascular function were assessed at both baseline and follow-up. Microbiome-derived metabolites were analyzed and gut microbiome samples were characterized by 16S rRNA gene analysis. We enrolled 40 patients, with 20 patients each in the ACS and CCS group. Alpha diversity of the microbiome did not differ throughout the follow-up. After ACS gut microbiome composition changed during the follow-up period with increased levels of Butyricicoccus and Butyricoccaceae, a pattern not observed in the CCS cohort. Downstream analysis of microbiome-derived metabolites SCFA revealed increased serum levels of butanoic acid, while TMAO levels remained unchanged. This small prospective observational non-randomized study, suggests that ACS may trigger an enrichment of butanoic acid-producing bacteria in the gut microbiome, accompanied by an increase in serum butanoic acid levels over 28 days. No significant changes in TMAO were observed. These insights could help develop approaches to reduce the burden of CVD. As a small pilot study, these findings require validation in larger ACS cohorts. Trial registration NCT, NCT05456802, Registered 30 June 2022, https://clinicaltrials.gov/study/NCT05122689.
In patients, severity of pressure-induced heart failure (HF) due to aortic stenosis and metabolic disorder correlates with thickness and mass of epicardial adipose tissue (EAT). We examined the role of the less studied pericardial adipose tissue (PAT) during manifestation and progression of pressure-induced HF in mice. Progressive remodeling was assessed in C57BL/6 J males, aged 9 weeks, following sham surgery or transverse aortic constriction (TAC) for 1 week (early pressure-overload), 8 (chronic pressure-overload), or 12 weeks (HF with reduced ejection fraction, HFrEF) with or without concomitant PAT excision. PAT removal did not affect early (1-week TAC) or chronic (8 weeks) pressure-overload-induced concentric remodeling. However, initial PAT excision prevented lung congestion, progressive LV dilation and systolic dysfunction and thereby protected against transition to HFrEF. This protection was associated with alleviation of early TAC-induced pro-inflammatory monocyte and macrophage expansion, attenuation of persistent pro-hypertrophic, pro-inflammatory and pro-fibrotic LV gene expression and the reduction of microscar and perivascular fibrosis in the long term. The latter was reflected by reduced peri-coronary accumulation of pro-fibrotic CD206+ macrophages, and prevention of periostin upregulation. Moreover, PAT protein directly activated naïve cardiac fibroblasts in vitro while bulk RNAsequencing revealed the initiation of an extracellular matrix deposition, monocyte recruiting, and macrophage activation program in the PAT early upon TAC. Our data suggest that PAT does not exert crucial impact on pressure-induced hypertrophy, while its removal counteracts HFrEF manifestation in mice, at least in part, by preventing excessive fibrotic responses suggested to derive from reciprocal fibroblast-macrophage interactions.
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