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Abstract Objective We aimed to summarize the association between gestational diabetes mellitus (GDM) and its intergenerational cardiovascular diseases (CVDs) impacts in both mothers and offspring post-delivery in existing literature. Methods PubMed, Embase, Web of Science, and Scopus were utilized for searching publications between January 1980 and June 2024, with data extraction and meta-analysis continuing until 31 July 2024. Based on a predefined PROSPERO protocol, studies published as full-length, English-language journal articles that reported the presence of GDM during pregnancy and its association with any CVD development post-delivery were selected. All studies were evaluated using the Newcastle-Ottawa Scale. Maximally adjusted risk estimates were pooled using random-effects meta-analysis to assess the risk ratio (RR) of GDM, and overall and subtypes of CVDs in both mothers and offspring post-delivery. Results The meta-analysis was based on 38 studies with a total of 77,678,684 participants. The results showed a 46% increased risk (RR 1.46, 95% CI 1.34–1.59) for mothers and a 23% increased risk (1.23, 1.05–1.45) for offspring of developing overall CVDs after delivery, following a GDM-complicated pregnancy. Our subgroup analysis revealed that mothers with a history of GDM faced various risks (20% to 2-fold) of developing different subtypes of CVDs, including cerebrovascular disease, coronary artery disease, heart failure, and venous thromboembolism. Conclusions These findings underscore the heightened risk of developing various CVDs for mothers and offspring affected by GDM, emphasizing the importance of preventive measures even right after birth to mitigate the burden of CVDs in these populations.

Emerging evidence indicates the critical roles of microbiota in mediating host cardiac functions in ageing, however, the mechanisms underlying the communications between microbiota and cardiac cells during the ageing process have not been fully elucidated. Bacterial DNA was enriched in the cardiomyocytes of both ageing humans and mice. Antibiotic treatment remarkably reduced bacterial DNA abundance in ageing mice. Gut microbial DNA containing extracellular vesicles (mEVs) were readily leaked into the bloodstream and infiltrated into cardiomyocytes in ageing mice, causing cardiac microbial DNA enrichment. Vsig4+ macrophages efficiently block the spread of gut mEVs whereas Vsig4+ cell population was greatly decreased in ageing mice. Gut mEV treatment resulted in cardiac inflammation and a reduction in cardiac contractility in young Vsig4-/- mice. Microbial DNA depletion attenuated the pathogenic effects of gut mEVs. cGAS/STING signaling is critical for the effects of microbial DNA. Restoring Vsig4+ macrophage population in ageing WT mice reduced cardiac microbial DNA abundance and inflammation and improved heart contractility.