Post-infarction cardiovascular remodeling and heart failure are the leading cause of myocardial infarction (MI)-driven death during the past decades. Experimental observations have involved intestinal microbiota in the susceptibility to MI in mice; however, in humans, identifying whether translocation of gut bacteria to systemic circulation contributes to cardiovascular events post-MI remains a major challenge. Here, we carried out a metagenomic analysis to characterize the systemic bacteria in a cohort of 49 healthy control individuals, 50 stable coronary heart disease (CHD) subjects, and 100 ST-segment elevation myocardial infarction (STEMI) patients. We report for the first time higher microbial richness and diversity in the systemic microbiome of STEMI patients. More than 12% of post-STEMI blood bacteria were dominated by intestinal microbiota (Lactobacillus, Bacteroides, and Streptococcus). The significantly increased product of gut bacterial translocation (LPS and d-lactate) was correlated with systemic inflammation and predicted adverse cardiovascular events. Following experimental MI, compromised left ventricle (LV) function and intestinal hypoperfusion drove gut permeability elevation through tight junction protein suppression and intestinal mucosal injury. Upon abrogation of gut bacterial translocation by antibiotic treatment, both systemic inflammation and cardiomyocyte injury in MI mice were alleviated. Our results provide the first evidence that cardiovascular outcomes post-MI are driven by intestinal microbiota translocation into systemic circulation. New therapeutic strategies targeting to protect the gut barrier and eliminate gut bacteria translocation may reduce or even prevent cardiovascular events post-MI.

Excessive gestational weight gain (GWG) is a potential risk factor for hypertensive disorders of pregnancy (HDP). We systematically reviewed three electronic databases for relevant articles published in English: PubMed, EMBASE and Web of Science. The Newcastle-Ottawa Scale was used to assess study quality. Random-effects meta-analyses were performed to supply a pooled estimation of the OR comparing the risk of HDP among healthy pregnant women with and without excessive GWG. The pooled estimation for the association between excessive GWG and the risk of HDPs yielded an odds ratio (OR) of 1.79 (95% CI: 1.61–1.99). A subgroup analysis showed that women who had excessive GWG were more likely to have an HDP (OR 1.82; 95% CI 1.53–2.17), preeclampsia (OR 1.92; 95% CI 1.36–2.72), or gestational hypertension (OR 1.67; 95% CI 1.43–1.95). The pooled estimation for the association between excessive GWG and the risk of HDPs among pregestational normal weight women yielded an OR of 1.57 (95% CI 1.26–1.96). A subgroup analysis showed that women who had excessive GWG were more likely to have HDP (OR 1.45; 95% CI 1.09–1.92) or gestational hypertension (OR 1.51; 95% CI 1.22–1.86). The summary ORs of pre-gestational underweight women and pre-gestational overweight and obese women were 2.17 (95% CI 1.56–3.02) and 1.32 (95% CI 1.08–1.63), respectively. The findings of this study suggest that excessive GWG in accordance with the IOM recommendations influences the rate of HDP.

Context: Silicosis is a devastating, irreversible lung fibrosis condition exposed to crystalline silica. The mononuclear phagocyte system plays an important role in the pathogenesis of silicosis. Objective: The present study was aimed to explore the dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in experimental silicosis model. Materials and methods: A mouse model of lung fibrosis was developed with crystalline silica particles (2 mg/40 μL via oropharyngeal instillation) using male C57BL/6 mice, and were killed on days 1, 3, 7, 14, and 28. The lung inflammation and fibrosis was investigated using hematoxylin–eosin staining and bronchoalveolar lavage fluid (BALF) analysis, Masson’s trichrome staining, and immunofluorescence. Circulating monocyte subsets (Ly6C^hi and Ly6C^lo), polarization state of BALF-derived alveolar macrophages (AMϕ) and lung interstitial macrophages (IMϕ, derived from enzymatically digested lung tissue) were analyzed by flow cytometry. Results: The percentage of Ly6C^hi monocytes significantly increased on day 1 after silica exposure, which reached the peak level from day 7 till day 28. Moreover, M2 (alternative activation) AMϕ (PI − CD64 + CD206+) was dramatically and progressively increased from day 1 to day 28. A parallel increase in IMϕ with M2 polarization (PI-CD64 + CD11b + CD206+) was also observed from day 1 to day 28. Conclusion: Our data demonstrate a dynamic view of mononuclear phagocyte change in three compartments after silica challenge, which highlights the remodeling of mononuclear phagocyte system as a potential therapeutic target for silicosis.