The roles of dipeptidyl peptidase-4 in the development and progression of abdominal aortic aneurysm

• Main Authors: Hsin-Ying Lu, 呂欣穎
• Other Authors: Chun-Che Shih
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/16016975678234439270

博士 === 國立陽明大學 === 臨床醫學研究所 === 104 === Abdominal aortic aneurysm (AAA) is a life-threatening situation affecting almost 10% of elders. There has been no effective medication for AAA other than surgical intervention. Still unclear the mechanism of AAA, the current literature suggests that AAA is characterized by the destruction of elastin and collagen in the media and adventitia via the infiltration of lymphocytes and macrophages. It has been indicated that chronic vascular inflammation is a hallmark of AAA. The main source of proteases from the infiltrated monocytes and macrophages into the vessel wall destroy the integrity of the aortic wall and degrade extracellular matrix (ECM), thus contributing to the development, progression and rupture of AAA. Dipeptidyl peptidase-4 (DPP-4), also known as lymphocyte cell surface marker CD26, has complex biological roles, including cell membrane associated activation of intracellular signal transduction pathways, cell-to-cell interaction, and enzymatic activity. DPP-4 plays an important role in various diseases, such as cancer, diabetes, atherosclerosis and some autoimmune diseases. The role of DPP-4, however, in AAA is unknown. The expression of the levels and enzymatic activity of DPP-4, even membrane-bond DPP-4, depends on the specific physiological or pathophysiological processes involved. This study showed that the relative intensity of DPP-4 in plasma significantly increased as AAA growth, which can be attenuated by the DPP-4 inhibitor, sitagliptin, via glucagon-like peptide-1 (GLP-1) action. Furthermore, the membrane-bond expression of CD26 on monocyte population significantly decreased in relation to aneurysm growth compared with control subjects, associating with monocyte-macrophage differentiation. From experimental study to clinical evidence, this study demonstrated that the multifunctional DPP-4 contributes an important role in AAA progression and development.