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Common Diabetes drug found effective in heart failure

Common Diabetes drug found effective in heart failure

USA: Metformin, a drug commonly used for the treatment of type 2 diabetes, might also be used for the treatment of heart failure with preserved ejection fraction (HFpEF), according to a new study. HFpEF is a condition that is predicted to affect over 8% of people aged 65 or older by the year 2020.

The study, published in the Journal of General Physiology, shows that metformin relaxes titin, a key heart muscle protein, allowing proper filling of the heart with blood before pumping it to the body.

Nearly half of all heart failure patients are considered to have HFpEF, in which the heart can properly contract, but, because the wall of the left ventricle is stiffer than normal, it fails to fully relax between beats, reducing its capacity to fill with blood. This reduces blood supply to the rest of the body, leading to shortness of breath with exertion and difficulty exercising.

HFpEF is more common in women, and other risk factors include hypertension, old age, and obesity. Unlike other forms of heart failure, however, there are currently no drugs available to treat HFpEF.

Also Read: Diabetes and Heart Failure: PURE study

Henk L. Granzier, Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona, and colleagues determined the therapeutic potential of metformin for improving diastolic function in a mouse model with HFpEF-like symptoms because the drug has been shown to increase left ventricular dilation and lower heart failure rate in diabetes patients.

The researchers gave metformin to mice with HFpEF-like symptoms and found that the drug reduced left ventricular stiffness, thereby improving the animals’ capacity for exercise.

Also Read: Metformin prevents development of Hypertension in Diabetes: Journal of American Heart Association

The researchers determined that metformin relaxes the left ventricle by making a heart muscle protein called titin more compliant. Titin acts like a molecular spring that helps the muscle recoil after it is stretched, and titin’s stiffness can be tweaked by enzymes that add phosphate groups to the protein’s spring-like elements. One of these elements, known as the N2B element, contains abnormally few phosphate groups in HFpEF patients, making titin extra stiff. But Granzier and colleagues found that metformin treatment increased the number of phosphate groups in the N2B element of mouse titin, causing the protein, and the heart muscle as a whole, to become more compliant.

“We, therefore, conclude that metformin is a potential therapy for patients with HFpEF,” Granzier says. “Because the drug is already approved and well tolerated in humans, using it to target titin stiffness presents a unique opportunity for immediate translation to the clinic.”

For further reference follow the link: 10.1085/jgp.201812259

Source: With inputs from Journal of General Physiology

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