Vascular complications in cardiometabolic disease – Team Zhichao Zhou

Vascular complications are a leading cause of morbidity and mortality, placing patients at high risk for life-threatening events such as myocardial infarction and stroke. The underlying mechanisms driving these complications remain poorly understood. Current therapies and biomarkers are inadequate for prevention and diagnosis. This highlights the urgent need to identify novel disease mechanisms, effective therapeutic targets, and reliable biomarkers to improve treatments and predict outcomes.

Our research

A central and early driver of vascular complications is endothelial dysfunction, marked by increased oxidative stress and reduced bioavailability of nitric oxide—an essential molecule for maintaining healthy blood vessels.

Cardiovascular research has predominantly focused on the vasculature, overlooking the role of circulation and circulating cells in endothelial regulation. Historically regarded as passive oxygen transporters, red blood cells (RBCs) have now emerged as active regulators of vascular homeostasis. My previous work revealed a paradigm-shifting role of RBCs in cardiovascular health, demonstrating their significant contribution to endothelial dysfunction in type 2 diabetes and their potential as biomarker sources.

Red blood cells have emerged as important mediators of endothelial dysfunction in various cardiometabolic diseases. Red blood cells contain diverse and abundant non-coding RNAs including microRNA, long non-coding RNAs and circular RNAs, whose functions re
Red blood cells have emerged as important mediators of endothelial dysfunction in various cardiometabolic diseases. Red blood cells contain diverse and abundant non-coding RNAs including microRNA, long non-coding RNAs and circular RNAs, whose functions remain largely unexplored. It is hypothesized that alteration of red blood cell-derived non-coding RNAs promotes oxidative stress and reduces nitric oxide bioavailability driving endothelial dysfunction. Photo: Zhichao Zhou

RBCs are rich in non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, yet their role in vascular health is poorly understood. Our translational study combines high-throughput ncRNA profiling with functional validations in RBCs from well-characterized patient cohorts to elucidate how RBC-derived ncRNAs drive endothelial dysfunction. We further test promising ncRNAs as therapeutic targets and biomarkers for assessing endothelial dysfunction and predicting cardiovascular risk. In collaboration with clinicians, translational and basic researchers, our research team aims to uncover how RBCs affect vascular health and establish targeting RBC-derived ncRNAs as a new strategy for preventing and predicting cardiovascular complications.

Publications

All publications from group members