Researchers discovered that a new protein, called pre-kallikrein (PK), is a potential therapeutic target for the vascular complications associated with type 1 diabetes. The study, titled “Plasma Prekallikrein is Associated with Carotid Intima-Media Thickness in Type 1 Diabetes,” was published in the journal Diabetes.
Previously reported as a marker for diabetic vascular disease of the kidneys, a team of researchers from the Medical University of South Carolina (MUSC), the American University of Beirut (AUB), and Case Western Reserve University, investigated whether PK was an independent risk factor for the development of whole-body vascular complications in diabetic patients.
The team analyzed data from the cohort of type 1 diabetic patients who took part in the Diabetes Control and Complications Trial/Epidemiology and Diabetes Intervention and Complications (DCCT/EDIC) study. The levels of PK in the blood were measured in 635 patients (corresponding to between years 3 and 5 of the EDIC study). The risk for cardiovascular disease was detected by a non-invasive technique (B-mode ultrasonography in EDIC years 1 and 6) that measures patients’ common and internal carotid intima-media thickness. (The carotid arteries are major blood vessels in the neck that supply blood to the brain, neck, and face, and intima-media are a vessel’s inner layers.)
The team discovered that increasing PK levels associated with increased thickness of intima-media in the vasculature of the carotids in type 1 diabetic patients.
PK belongs to the family of kallikrein-kinin proteins that are present in the wall of blood vessels. They induce, in healthy vessels, a sequence of molecular signals that reach the interior, and modulate vessels’ dilation and tension. In diabetic patients, however, cells of the intima-media reach the surface of the blood vessels, contacting PK directly and leading to a chronic inflammation that results in blood vessel thickening (a phenomenon observed in diabetic kidney disease but also in other pathologies, including retinopathy and atherosclerosis).
The results showed that high blood PK levels regulate the thickening of blood vessels observed in type 1 diabetes patients. However, an open question remains: are the high PK levels causing arteries to thicken or do thickened arteries lead to an increase in PK blood levels?
While further investigation is necessary to answer this question, “[t]hese preclinical studies not only will give us insights into the involvement of plasma PK in vascular disease but will also contribute to development of novel treatment strategies for diabetic vascular disease,” concluded Ayad A. Jaffa, PhD, the study’s lead author in a press release.