The role of hemoglobin alpha in diabetes-related vascular dysfunction

Scientific Abstract
Hemoglobin, the oxygen carrying protein expressed in erythrocytes, can be glycated following elevations in blood
glucose. Some amino acids, such as the N-terminal valine of the hemoglobin beta chain are highly susceptible
to glycation in diabetic patients. This specific glycated isoform, termed HbA1c, has been used by clinicians as
an overall picture of a diabetic patient’s ability to control their glucose over a 3-month period and as an indicator
for future cardiovascular risks. Recently, it was observed that the alpha chain of hemoglobin, but not the beta
chain, is expressed in endothelial cells lining arteries where it interacts with endothelial nitric oxide synthase
(eNOS) to modulate nitric oxide (NO) release. Hemoglobin alpha is known to be glycated at a number of sites,
including one in the putative eNOS interaction domain. Since it is well recognized that vascular dysfunction
underlies many of the pathologies in diabetic patients, it was hypothesized that the hemoglobin alpha expressed
in the endothelium will have aberrant function in diabetes mellitus, likely due to a glycation event. The aim of the
current proposal is to examine the role of hemoglobin alpha and any possible glycated forms of hemoglobin
alpha in the endothelium of a murine model of diabetes. Using pharmacological and genetic approaches, the
interaction between hemoglobin alpha and eNOS will be disrupted and the influence on the development of
vascular dysfunction will be explored. This work has the potential to identify both a novel biomarker of vascular
risk and also a potential therapeutic target for pharmacological treatments.

Grant Number: 5R01HL155618-05
NIH Institute/Center: NIH
Principal Investigator: Pooneh Bagher