24 January 2022
Molecular details of the role of a specific protein that is part of a channel in cell membranes offer new insights into the function of blood vessels in health and disease. The findings may be relevant to several medical conditions, including high blood pressure, diet-induced type 2 diabetes, and vascular problems associated with obesity.
Dr. Ahmad Alghanem at King Saud bin Abdulaziz University for Health Sciences, together with colleagues at several research centres in the US, have been investigating the role of the LRRC8A (SWELL1) protein. They had previously shown that the protein is an essential part of the Volume-Regulated Anion Channel (VRAC), which controls the flow of negatively charged ions (anions) through cell membranes.
The team has now performed further studies using endothelial cells from the veins of human umbilical cord tissue. Human Umbilical Vein Endothelial Cells (HUVECs) are widely studied to investigate the activity of the endothelium, a single layer of cells that lines the interior of regions of the body including all blood vessels. It plays an important role in regulating blood pressure, blood flow, and the contractile activity of muscle cells surrounding blood vessels. Endothelial cells are also crucial to the formation of new blood vessels, known as angiogenesis.
The new research has uncovered proteins that LRRC8A interacts with and molecular signalling pathways that it controls. The results suggest that LRRC8A plays a wide and multi-faceted in the normal functioning of blood vessels, including the maintenance of healthy blood pressure. Impairments in the activity of LRRC8A could be linked to problems with insulin signalling associated with the insulin resistance found in type 2 diabetes.
The research also revealed what the authors describe as “curious observations” that suggest there is more to learn about LRRC8A and its role in the vascular system. One possibility requiring further investigation is whether the protein and the VRAC channel as a whole may be involved in sensing fluid flow and fluid pressure within blood vessels. This mechanoresponsive activity may be a significant aspect of blood pressure control, which could be of major significance for many patients.
While the work is fundamental research, rather than applied science, the new insights into the control of blood vessel activity could eventually lead to a better understanding of vascular diseases and possible new avenues towards treatments.
Alghanem, A. F. et al. The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS signaling and vascular function. eLife 10:e61313 (2021). | article