Study finds how diabetes leads to vascular disease

Washington DC: A team of scientists and doctors has identified a cellular link between diabetes and one of its major complications – narrowing of blood vessels – that increases the risk of several serious health problems, including heart disease and stroke. . The same team previously discovered that hyperglycemia, a symptom characteristic of diabetes, activates an enzyme called protein kinase A (PKA), which increases the activity of calcium channels and contracts blood vessels.

"It was a surprise, because PKA is usually badociated with widening blood vessels and is not really part of our radar. We wanted to understand the molecular processes behind this opposite reaction, "said lead author Manuel Navedo.

For the new study published in the journal Clinical Investigation, the team conducted a series of experiments on the effects of high glucose levels on the cerebral blood vessels and arterial cells that control blood flow. The tests were performed on mice and two mouse models of genetically modified diabetes, developed for cardiovascular health studies.

The researchers focused on the relationship between PKA and adenylyl cyclase (AC), an enzyme involved in the production of cyclic AMP (cAMP), a cellular messenger playing a vital role in cell function vascular.

Their results showed that one AC in particular, activation of AMPP and AC5-mediated PKA resulted in increased calcium channel activity and narrowing of blood vessels. They also found that AC5 was essential for constricting blood vessels during diabetes.

The team now hopes to test the effects of the AC5 chain reaction under high glucose conditions in human cells. This step could confirm that there is a target treatment to reduce vascular complications of diabetes including ocular, renal, cerebral, gastrointestinal and cardiovascular diseases.

"Every day in our clinics we see the devastating impact of diabetes on the health and lives of our patients, and our work clearly shows how high blood sugar can damage the vascular system and gives us a new target for block its effects, "said co-author Nipavan Chiamvimonvat.