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Pioneering insights: Does iron protect against arteriosclerosis?
According to experts, around four million people in Germany suffer from arteriosclerosis (atherosclerosis or hardening of the arteries), but only every third person is diagnosed with the disease. The arterial bottlenecks can result in serious complications. Researchers from Austria have now gained new knowledge about the disease.
According to a recent announcement by the Medical University of Innsbruck, the first-time detection of direct interactions between iron metabolism and lipid balance could pave a new therapeutic way to lower LDL cholesterol levels and thus optimize the prevention of cardiovascular diseases.
Increased risk of atherosclerosis
The findings published in the renowned specialist journal "European Heart Journal" are based on the longstanding collaboration of Innsbruck research teams around the internist and iron expert Günter Weiss from the Medical University of Innsbruck.
The starting point of this research work was the surprising discovery that carriers of a mutated HFE gene - changes in this protein trigger hereditary hemochromatosis (genetic iron overload) - have low LDL cholesterol levels.
"Surprisingly, because people with the genetic iron storage disease, incidentally the most common recessive inherited disease in Europeans, were attributed an increased risk of atherosclerosis due to iron deposits in the vessels," explains the director of the Innsbruck University Clinic for Internal Medicine II, Günter Weiss .
"So far there has been disagreement among experts as to whether iron overload has positive or negative effects on the cardiovascular risk profile," says the scientist, who has been researching iron metabolism and associated diseases for many years.
Administration of an iron diet
In a knockout mouse model with an iron overload and a cholesterol level that was adapted to the human organism and was established in Günter Weiss' laboratory, the research team was able to determine after the administration of an iron diet that the mice developed less atherosclerosis.
The Innsbruck scientists were also able to detect low LDL values in over 200,000 human samples from HFE gene carriers from various biodatabases and genome-wide association studies.
"In our investigations, we finally identified three mechanisms that clarify this connection," said Ivan Tancevski from the team.
“We were able to demonstrate that the hemochromatose protein HFE regulates the expression of the LDL receptor on liver cells by making it available on the cell membrane and that Kupffer cells, which are the scavenger cells of the liver, also express LDL receptors and thus on the metabolism of the LDL Cholesterol are involved, ”explains the researcher.
"After all, iron is responsible for the transfer of blood lipids from these Kupffer cells by upregulating the transport protein ABCA1 so that LDL is removed from the serum," adds Egon Demetz, first author of the work, the physiological details.
New treatment approach
The Innsbruck researchers now want to use the clarification of this connection for new strategies for the therapeutic prevention of atherosclerosis.
“Especially in the context of familial hypercholesterolemia, in which a genetic defect limits the function of the LDL receptor, it is conceivable to force this interaction between the HFE protein, the Kupffer cells and iron in order to transport more LDL out of the serum and lower cholesterol levels, ”explains Weiss. (ad)
Author and source information
This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
- Medical University of Innsbruck: Does iron protect against atherosclerosis ?, (accessed: April 21, 2020), Medical University of Innsbruck
- Egon Demetz, Piotr Tymoszuk, Richard Hilbe, Chiara Volani, David Haschka, Christiane Heim, Kristina Auer, Daniela Lener, Lucas B Zeiger, Christa Pfeifhofer-Obermair, Anna Boehm, Gerald J Obermair, Cornelia Ablinger, Stefan Coassin, Claudia Lamina, Juliane Kager, Verena Petzer, Malte Asshoff, Andrea Schroll, Manfred Nairz, Stefanie Dichtl, Markus Seifert, Laura von Raffay, Christine Fischer, Marina Barros-Pinkelnig, Natascha Brigo, Lara Valente de Souza, Sieghart Sopper, Jakob Hirsch, Michael Graber, Can Gollmann-Tepeköylü, Johannes Holfeld, Julia Halper, Sophie Macheiner, Johanna Gostner, Georg F Vogel, Raimund Pechlaner, Patrizia Moser, Medea Imboden, Pedro Marques-Vidal, Nicole M Probst-Hensch, Heike Meiselbach, Konstantin Strauch, Annette Peters, Bernhard Paulweber, Johann Willeit, Stefan Kiechl, Florian Kronenberg, Igor Theurl, Ivan Tancevski, Guenter Weiss: The haemochromatosis gene Hfe and Kupffer cells control LDL cholesterol homeostasis and impact on atherosclerosis development ; in: European Heart Journal, (published: 30.03.2020), European Heart Journal