Dresden International Graduate School for Biomedicine and Bioengineering

The interplay between organs is crucial for human health and significantly influences various diseases. This organ crosstalk is becoming increasingly important in clinical practice due to the rising number of elderly patients with multiple comorbidities. These comorbidities not only alter the clinical trajectory of individual diseases but also profoundly affect therapeutic outcomes. For instance, Type 2 diabetes mellitus (T2DM) often coexists with chronic kidney disease (CKD), leading to common cardiovascular complications. Patients suffering from T2DM or CKD frequently develop heart failure, resulting in mortality primarily from sudden cardiac death or ischemic heart disease—conditions exacerbated by premature vascular and cardiac aging characterized by cardiovascular calcification, fibrosis, and hypertrophy. This scenario underscores a shared pathophysiological pathway that warrants further investigation.

Arterial calcification—defined as pathological calcific mineral deposition within arteries—is a major understudied mechanism of cardiovascular diseases strongly linked to poor outcomes. The fibro-calcific remodeling of highly flexible cardiovascular tissues disrupts normal biomechanical function, directly impacting cardiovascular complications.

Maintaining metabolic homeostasis is vital in the bidirectional interaction between the cardiovascular system and kidneys. The cardiovascular-renal-metabolic syndrome, prevalent among obese individuals, is strongly associated with an elevated risk of cardiovascular diseases, emphasizing the critical role of organ interactions in sustaining homeostasis. Organ communication occurs through mediators facilitating inter-organ signaling; however, while some insights into organ crosstalk exist, detailed mechanisms remain largely unexplored. Recent studies indicate that extracellular vesicles play a pivotal role alongside traditional hormones.

In a multidisciplinary approach, my colleagues and I have discovered a novel mechanism demonstrating that extracellular vesicles with high calcification potential significantly regulate the formation of microcalcifications. At the molecular level, we have shown that intracellular trafficking processes and post-translational modifications of the lysosomal sorting receptor sortilin regulate the calcification potential of these vesicles. We are currently investigating the role of NOX-mediated redox status and the role of endomembrane maturation on the calcification propensity of extracellular vesicles, the molecular and functional mechanism that mediates the loading of pro-calcifying cargo molecules into extracellular vesicles, and the importance of calcified extracellular vesicles on intercellular communication during inflammation. Additionally, we are exploring the biogenesis of subpopulations of extracellular vesicles contributing to fibro-calcifying remodeling in vascular and renal dysfunction. Our research also includes clinically translational approaches to understand cardiovascular calcification development in patients with chronic renal insufficiency and diabetes mellitus while examining post-translational modifications.

Our methodology integrates both in vitro and in vivo studies alongside cutting-edge omics strategies.