Red blood cell enzyme may promote endothelial dysfunction in diabetics
Swedish researchers have identified a potential mechanism for the endothelial dysfunction found in patients with type 2 diabetes (T2D): increased expression of the arginase I protein in red blood cells.
The enzyme expression was elevated in cells from diabetic patients and more upregulation of reactive oxygen species (ROS) was noted in those cells compared to ones from healthy individuals, the authors reported in the Journal of the American College of Cardiology.
Lead researcher Zhichao Zhou, MD, PhD, and colleagues incubated red blood cells from individuals with T2D—along with those of age-matched healthy controls—inside experimental models of healthy human blood vessels. They also performed similar testing in rats which mimicked the condition of T2D.
“We found that healthy blood vessels exposed to red blood cells from patients with type 2 diabetes suffer damage to their innermost cell layers, the endothelial cells,” senior author John Pernow, MD, PhD, said in a press release. “This phenomenon, which is called endothelial dysfunction, appears early on in the development of diabetes-related vessel injury and greatly reduces the ability of the vessels to dilate while aggravating the inflammation.”
The lack of dilation may be due to the reduced production of nitric oxide (NO) in T2D red blood cells, the authors explained. But attempts to reverse this process were successful in the experimental vessels.
“We … found that treatment that targeted arginase or oxygen-derived free radicals normalized red blood cell function, which meant that their harmful effect on cardiovascular function could be prevented,” Pernow said. “Our hope is that this knowledge will give rise to new treatments, specifically targeted at red blood cells, that prevent vascular injury and protect the heart in the event of heart attack in patients with type 2 diabetes.”
In an accompanying editorial, Gemma Vilahur, PhD, said additional challenges must be overcome before red blood cell (RBC)-targeting therapies are available. Specifically, she pointed to the need for “isoform-specific arginase inhibitors and the ability to target erythrocytes exclusively.” Blocking arginase I in the liver may lead to unwanted side effects, she said, given the protein’s important function in that organ.
Still, Vilahur described the possibility of a new therapeutic option for RBC arginase as “appealing.”
“Overall, the study by Zhou et al. provides evidence that a new contributor to endothelial dysfunction in T2DM has been identified,” Vilahur wrote. “The degree to which erythrocytes impair NO availability has yet to be determined. However, there is no doubt that RBCs deserve attention in patients with T2DM.”
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.