Metabolites and metabolism in vascular calcification: links between adenosine signaling and the methionine cycle. American journal of physiology. Heart and circulatory physiology The global population of individuals with cardiovascular disease is expanding, and a key risk factor for major adverse cardiovascular events is vascular calcification. The pathogenesis of cardiovascular calcification is complex and multifaceted, with external cues driving epigenetic, transcriptional, and metabolic changes that promote vascular calcification. This review provides an overview of some of the lesser understood molecular processes involved in vascular calcification and discusses the links between calcification pathogenesis and aspects of adenosine signaling and the methionine pathway; the latter of which salvages the essential amino acid methionine, but also provides the substrate critical for methylation, a modification that regulates the function and activity of DNA and proteins. We explore the complex and dynamic nature of osteogenic reprogramming underlying intimal atherosclerotic calcification and medial arterial calcification (MAC). Atherosclerotic calcification is more widely studied; however, emerging studies now show that MAC is a significant pathology independent from atherosclerosis. Furthermore, we emphasize metabolite and metabolic-modulating factors that influence vascular calcification pathogenesis. Although the contributions of these mechanisms are more well-define in relation to atherosclerotic intimal calcification, understanding these pathways may provide crucial mechanistic insights into MAC and inform future therapeutic approaches. Herein, we highlight the significance of adenosine and methyltransferase pathways as key regulators of vascular calcification pathogenesis. 10.1152/ajpheart.00267.2024

Role of gut microbiota-derived metabolites on vascular calcification in CKD. Yin Li,Li XiaoXue,Ghosh Sounak,Xie Changming,Chen Jie,Huang Hui Journal of cellular and molecular medicine The interaction between gut microbiota and the host has gained widespread concern. Gut microbiota not only provides nutrients from the ingested food but also generates bioactive metabolites and signalling molecules to impact host physiology, especially in chronic kidney disease (CKD). The development of CKD, accompanied by changed diet and medication, alters the gut flora and causes the effect in distant organs, leading to clinical complications. Vascular calcification (VC) is an actively regulated process and a high prevalence of VC in CKD has also been linked to an imbalance in gut microbiota and altered metabolites. In this review, we focused on gut microbiota-derived metabolites involved in VC in CKD and explained how these metabolites influence the calcification process. Correcting the imbalance of gut microbiota and regulating microbiota-derived metabolites by dietary modification and probiotics are new targets for the improvement of the gut-kidney axis, which indicate innovative treatment options of VC in CKD. 10.1111/jcmm.16230