动脉粥样硬化 z-bo 2020-11-23 366

　　Researchers at Karolinska Institutet in Sweden pointed out in a research report published in the Proceedings of the National Academy of Sciences (PNAS) that drugs used to treat overactive bladder can accelerate atherosclerosis in mice. According to the researchers, the results of the study indicate that in some cases, this drug may increase the risk of cardiovascular disease and stroke in humans.

　　Drugs developed to treat specific diseases may have other pathophysiological effects. Researchers at Karolinska Institutet in Sweden and their colleagues at Shandong University in China now show that drugs used to treat overactive bladder may be related to atherosclerosis.

　　The substance is called mirabegron, which relaxes the bladder muscles by stimulating the sympathetic nervous system in the brain. In a study published in PNAS, the researchers showed that the substance also affects the fat tissue of mice, activates brown fat and triggers the conversion of white fat into brown fat. The dose received by animals corresponds to the dose given to humans.

　　"The drug is administered to mice lacking certain transport molecules for blood lipids and cholesterol, and therefore used as an animal model of atherosclerosis (mice have modifications in the gene of protein ApoE or the receptor of lipoprotein LDL). It was found that mirabegron accelerated the growth of atherosclerotic plaques, which is a common cause of heart attacks and strokes. The plaque has also become less stable.

　　"Treatment with mirabegron increases the blood levels of lipoproteins LDL and VLDL, which are commonly referred to as "bad" cholesterol, used to cause atherosclerotic plaques in arteries. These changes depend on lipolysis (lipolysis) and thermogenesis (thermogenesis) that occur when brown fat is activated.

　　"We link this drug to atherosclerosis through the mechanism of brown fat, and link it to the risk of diseases that affect blood flow into the brain, such as cardiovascular disease or stroke," said Yihai Cao, professor of the department. Lead the research at Karolinska Institutet in Microbiology, Tumor and Cell Biology.

　　Since this study was conducted on mice, the results cannot be directly transferred to humans. However, in view of a recently published study showing that Mirabegron can activate brown fat in the human body, Li Haihai believes that there are reasons for warning.

　　"Patients with cardiovascular disease or atherosclerosis should be careful when using this drug, because it may accelerate the growth of plaque and make it unstable," he said. "Because this drug increases the level of LDL in the blood, people who have mutations that make it difficult for the body to get rid of LDL may be particularly sensitive."

　　However, he pointed out that this hypothesis must be verified in human clinical studies. One in every 300 to 500 people has a mutation in the LDLR gene, which encodes the LDL receptor protein, which usually removes LDL from the blood.