Myeloid-Derived Suppressor Cells (MDSCs) in Cardiovascular Risk of Obesity-Associated Diabetes

Vollständiger Abstract

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The dysregulation of immune homeostasis and the persistence of chronic, low-grade inflammation represent core pathophysiological drivers governing the onset and progression of metabolic and cardiovascular disorders. Myeloid-derived suppressor cells (MDSCs) comprise a highly heterogeneous population of immature myeloid cells that are rapidly mobilized from the bone marrow in response to biological stressors, such as sustained tissue injury and chronic inflammatory signaling. Historically evaluated within oncology and infectious disease frameworks, accumulating evidence highlights the pivotal, context-dependent roles of MDSCs in cardiometabolic environments. In conditions of obesity and type 2 diabetes (T2D), MDSCs undergo substantial expansion and accumulation within peripheral tissues, including adipose tissue and the liver. Functionally, MDSCs act as dynamic immunoregulators that can either buffer metabolic inflammation, via the secretion of interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), and nitric oxide (NO) or, conversely, reflect and exacerbate disease progression depending on specific cellular subsets, glycemic control, and tissue localization. Within the vascular system, specific monocytic MDSC subsets demonstrate significant atheroprotective and cardioprotective capabilities by dampening Th1/Th17-mediated arterial wall inflammation, stabilizing atherosclerotic plaques, and preserving cardiac structural architecture during heart failure. However, phenotypic and functional heterogeneity poses a critical clinical challenge, as certain persistent or altered subsets correlate with heightened cardiovascular risk and adverse cerebrovascular outcomes. This review delivers a comprehensive synthesis of contemporary insights into MDSC biology at the intersection of obesity-associated diabetes and cardiovascular disease, characterizing their dualistic mechanisms, distinguishing preclinical causal mechanisms from human observational data. Moreover, we have established a comprehensive framework to reconcile the conflicting protective versus detrimental effects of MDSCs. And finally, we have also evaluated their potential clinical utility as candidate biomarkers, delineating the safety imperatives essential for translating MDSC-targeted therapeutic interventions into clinical practice.