(November 10, 2020) WEBINAR: Sugar Rush: How Diabetes Leads to Vascular Disease

Diabetes is a devastating disease affecting millions worldwide. Vascular complications are a major cause of morbidity and mortality in the diabetic population. Although much effort has been placed in examining mechanisms of endothelial dysfunction in diabetes, vascular smooth muscle complications are understudied. The L-type Ca²⁺ channel Ca_V1.2 plays key roles in vascular smooth muscle excitability, muscle contraction and gene expression. Exaggerated Ca_V1.2 activity has been implicated in the chain of events contributing to hyperglycemia-induced vascular complications during diabetes, but the mechanisms for this remains the subject of investigation.

In this webinar, Dr. Navedo discussed new data describing a previously unappreciated pathway that gets activated by hyperglycemic conditions and contributes to changes in vascular function. He presented evidence that activation of this pathway can contribute to changes in vascular smooth muscle Ca_V1.2 activity and vascular reactivity in animal models of diabetes and diabetic patients. The exquisite detail of the dissected signaling pathway and the link to vascular complications was made possible by the implementation of a multiscale approach that examines changes from the biochemical level to single-molecule biophysics to changes in cerebral blood flow and systemic blood pressure. For this, Dr. Navedo uses 1) sophisticated biochemistry to examine protein abundance and phosphorylation state of proteins, 2) electrophysiology to examine changes in ion channel activity, 3) super-resolution microscopy and PLA assay to define the spatial distribution of proteins, 4) pressure myography to examine effect of treatments on myogenic tone, 4) radio telemetry to measure blood pressure and 5) Laser Speckle imaging to explore the consequences of different treatments in blood flow regulation. With this approach, the research team can provide a comprehensive examination of hyperglycemia and diabetic effects in vascular smooth muscle that extend from the single-molecule to the whole animal level.

The key learning objectives were:

1) Understand what is arterial (myogenic) tone and the role of different ion channels involved.

2) Appreciate effects of hyperglycemia on Ca_V1.2 channel activity and vascular reactivity.

3) Describe mechanisms by which hyperglycemia modulates Ca_V1.2 channel activity and vascular reactivity from single-molecule events to whole-body physiology.

4) Implement a multiscale approach for any given research program.