Elucidation mechanism of hypercholesterolemia associated with H. pylori infection

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16476
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Oita University
• Principal Investigator: Ninomiya Ryo 大分大学, 医学部, 助教 (00794041)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ピロリ菌 / CagA / LDL受容体 / 高コレステロール血症

Outline of Final Research Achievements

Helicobacter pylori (H. pylori) infection mainly causes gastroduodenal diseases, including chronic gastritis, peptic ulcer disease and gastric cancer. Recently, some studies have demonstrated that infection with H. pylori, especially strains harboring the virulence factor CagA (cytotoxin-associated gene A), contribute to the development of non-gastric systemic diseases, including hypercholesterolemia and atherosclerotic cardiovascular diseases. However, the mechanism of H. pylori infection which causes systemic disease yet to be revealed.
This study confirmed that CagA and LDLR cause direct physical bonding to each other, and both proteins co-localize in the cell. Furthermore, we demonstrated that expression of CagA significantly reduced LDL uptake into the cells. This study provided some insight into the causal relationship between CagA-positive H. pylori infection, hypercholesterolemia and its association with ischemic heart disease.

Free Research Field

解剖学，分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ピロリ菌感染、特にCagA蛋白質をもつピロリ菌感染は胃炎、胃潰瘍、さらに胃癌を引き起こすばかりでなく、胃以外の全身性疾患の発症に関連することが知られていた。しかしながら、その臨床的重要性にも関わらず、ピロリ菌感染が全身性疾患を引き起こす機序は明らかになっていなかった。
本研究によって、CagAがLDLRとの物理的結合を介してLDLRの機能を阻害することが明らかとなり、ピロリ菌感染が高コレステロール血症から虚血性心疾患を引き起こすメカニズムの一端が解明された。この成果は、ピロリ菌によって全身性疾患が発症するメカニズムの最初の報告となり、今後新たな治療法の開発が期待される。