Hyperglycaemia could lead to heart attack complications

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The mechanism by which blood glucose levels can affect the contraction of blood vessels has been demonstrated for the first time by a team from the University of Leicester, UK.

The group, led by Richard Rainbow, Department of Cardiovascular Sciences, University of Leicester, UK, have shown that hyperglycaemia can cause blood vessels to contract more strongly than at physiologically normal blood sugar levels.

Using electrophysiology and myography techniques to examine the impact of glucose on arterial myocytes, the team has identified a mechanism that controls the narrowing of blood vessels.

High glucose at the time of heart attack could make coronary artery blockage more severe by causing the blood vessel to contract, leading to a higher risk of complications.

Richard Rainbow, lecturer in Cardiovascular Cell Physiology, says “We have shown that the amount glucose in the blood changes the behaviour of blood vessels, making them contract more than normal. This could result in higher blood pressure, or could reduce the amount of blood that flows through vital organs.

“We have identified a known signalling protein family, protein kinase C, is a key part of this enhanced contractile response, and have also shown in our experiments that we can restore the normal level of contractile response, and reverse the effects on the heart, with inhibitors of these proteins.

“This is the first study to show direct evidence of blood vessel contraction to glucose, and the potential mechanism behind this contractile response. In the experimental models we used in this study, including human blood vessels, increasing glucose to the levels that could be reached after a large meal altered vascular contraction.

“A large number of people who suffer a heart attack will have high glucose due to the ‘stress response’. This means that even people who are not diabetic may become hyperglycaemic during a heart attack.”

The research team have previously shown that high glucose from any cause, not just diabetes, is an indicator of a ‘worse outcome’ following a heart attack. Further research in by the Leicester group has shown that glucose has potentially damaging effects on the normal function of the heart, such as arrhythmia and abolishing the built-in protective mechanisms that the heart can activate on stress.

Rainbow adds, “Our studies show that glucose has an important physiological effect on the normal functioning of the cardiovascular system. Increases in blood sugar to pathophysiological levels cause marked changes in normal blood vessel and cardiac muscle behaviour that could be life-threatening if left untreated.

“Our data show a clear glucose-induced potentiation of contraction in blood vessels. Targeting the specific types of protein kinase C that we’ve shown to be involved in this can provide a novel therapeutic route for improving outcome in ischaemic diseases, such as heart attack or stroke.”

Jeremy Pearson, associate medical director at the British Heart Foundation, says, “This team have shown that, in multiple species, it is possible to use PKC as a target to block blood vessel constriction caused by high levels of glucose in the blood. This opens up the possibility for improved treatment for patients where recovery from heart attack is complicated by raised glucose levels.”