In a study conducted at the University of California, San Diego, a research group led by Assistant Professor Kunio Kawanishi of the University of Tsukuba found that the gene CMAH lost during human evolution may cause arteriosclerosis.
Arteriosclerosis is a disease that causes cardiovascular disease and cerebrovascular accidents.Aging, hyperlipidemia, hypertension, obesity, smoking, etc. are risk factors for cardiovascular disease.However, about 15% of first-time patients with cardiovascular disease do not have these factors.
On the other hand, sialic acid located at the end of the sugar chain that covers the cell surface of mammals includes Neu5Ac and Neu5Gc, and "CMP-Neu5Ac hydroxylase (CMAH)" converts Neu5Ac to Neu5Gc.Almost all mammals except humans have CMAH and synthesize sugar chains containing Neu5Gc.Humans are said to have lost the function of CMAH 2-3 million years ago and cannot synthesize Neu5Gc.Many microorganisms recognize the sialic acid located at the end of the sugar chain of the cell and infect the host. Due to the absence of Neu5Gc, even if humans coexist with other mammals, they are less likely to suffer from zoonotic diseases.
The research group found that CMAH-deficient mice, which, like humans, cannot synthesize Neu5Gc, form more advanced arteriosclerotic lesions than wild-type mice.Various analyzes and studies have shown that overdose of lean meat (beef, pork, mutton, etc.) is a risk factor for cardiovascular disease and colorectal cancer.Humans have anti-Neu5Gc antibodies, and lean meat is high in Neu5Gc.Therefore, it was found that when anti-Neu5Gc antibody was induced in CMAH-deficient mice and a diet containing Neu5Gc was given, arteriosclerosis worsened compared with other experimental conditions.
This suggests that the accumulation of Neu5Gc due to the intake of lean meat in humans and the microinflammation caused by the anti-Neu5Gc antibody may be involved in the development of arteriosclerosis.In the future, it is expected to develop new preventive methods and treatment strategies for arteriosclerosis and colorectal cancer.
Paper information:[Proceedings of the National Academy of Sciences of the United States of America] Human species-specific loss of CMP-N-acetylneuraminic acid hydroxylase enhances atherosclerosis via intrinsic and extrinsic mechanisms