Genetic engineering could protect implantable heart valve from destruction

International study led by Dr. Vered Padler-Karavani from Tel Aviv University

showed that the destruction of implantedbioprosthetic heart valves occur due to tissue calcification caused by the immune response to foreign animal sugars. Scientists have proposed using genetic engineering to modify animals from which tissue is taken for transplantation.

Heart valve defects are the most commondisease of the cardiovascular system. Heart defects affect about 2% of the population in developed countries. Almost half of these diseases are aortic valve stenoses. Therapeutic heart valve replacement is the second most popular heart surgery after coronary artery bypass surgery.

Researchers explain that currentlyPatients can be implanted with either mechanical heart valves or biological prosthetic heart valves made from bovine, porcine, or equine tissue. Mechanical implants last a long time, but require daily use of anticoagulants. Biological prostheses allow patients to live a normal life, but typically break down within ten years and require replacement.

“Since bioprosthetic heart valves are madefrom animal tissues, we hypothesized that they contain sugars foreign to humans (Neu5Gc and alpha-Gal), which are attacked by the patient’s immune system,” says Padler-Karavani. “Our studies confirmed this hypothesis.”

About 1,700 people took part in the studypatients from whom 5 thousand blood samples were obtained at different times after implantation. The scientists note that all patients developed an immune response against foreign sugars.

To prevent an immune reaction andCalcification of the implant, scientists proposed using genetic engineering. Researchers have created genetically modified pigs that do not produce sugars that are foreign to humans. Experiments conducted in an artificial environment have shown that tissue obtained from such pigs is significantly less calcified, even in the presence of antibodies against these sugars.

“This study marks a technologicalbreakthrough in the field of artificial heart valves and provides a deep understanding of the mechanisms leading to structural valve wear, notes Padler-Karavani. "Our results could lead to a significant improvement in the quality of life of many patients with cardiovascular problems."

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