Pleiotropic activities of succinate: The interplay between gut microbiota and cardiovascular diseases

Cardiovascular diseases (CVDs) continue to be a significant contributor to global mortality, imposing a substantial burden and emphasizing the urgent need for disease control to save lives and prevent disability. With advancements in technology and scientific research, novel mechanisms underlying CVDs have been uncovered, leading to the exploration of promising treatment targets aimed at reducing the global burden of the disease. One of the most intriguing findings is the relationship between CVDs and gut microbiota, challenging the traditional understanding of CVDs mechanisms and introducing the concept of the gut-heart axis. The gut microbiota, through changes in microbial compositions and functions, plays a crucial role in influencing local and systemic effects on host physiology and disease development, with its metabolites acting as key regulators. In previous studies, we have emphasized the importance of specific metabolites such as betaine, putrescine, trimethylamine oxide, and N,N,N-trimethyl-5-aminovaleric acid in the potential treatment of CVDs. Particularly noteworthy is the gut microbiota-associated metabolite succinate, which has garnered significant attention due to its involvement in various pathophysiological pathways closely related to CVDs pathogenesis, including immunoinflammatory responses, oxidative stress, and energy metabolism. Furthermore, we have identified succinate as a potential biomarker, highlighting its therapeutic feasibility in managing aortic dissection and aneurysm. This review aims to comprehensively outline the characteristics of succinate, including its biosynthetic process, summarize the current evidence linking it to CVDs causation, and emphasize the host-microbial crosstalk involved in modulating CVDs. The insights presented here offer a novel paradigm for future management and control of CVDs. Current studies have suggested the pleiotropic functions of succinate in vascular endothelial injury, vascular smooth muscle cell proliferation and migration, ischemia-reperfusion injury, macrophage polarization, aortic aneurysm and dissection, regulation of the renin-angiotensin system, cardiomyocyte hypertrophy, etc.Highlightsimage Cardiovascular diseases (CVDs) continue to be a significant contributor to global mortality, imposing a substantial burden and emphasizing the urgent need for disease control to save lives and prevent disability.The gut microbiota, through changes in microbial compositions and functions, plays a crucial role in influencing local and systemic effects on host physiology and disease development, with its metabolites acting as key regulators.Gut microbiota-associated metabolite succinate involves in various pathophysiological pathways closely related to CVDs pathogenesis, including immunoinflammatory responses, oxidative stress, and energy metabolism.The burgeoning evidence surrounding the role of succinate in the gut microbiome carries significant implications for our comprehension of host-microbiome interactions and the development of new treatments for CVDs.