Overexpression of STAMP2 suppresses atherosclerosis and stabilizes plaques in diabetic mice.
Our research aims to evaluate the function of the STAMP2 gene, an important trigger in insulin resistance (IR), and explore its role in macrophage apoptosis in diabetic atherosclerotic vulnerable plaques. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. The level of STAMP2 was measured by RT-PCR and Western blot. The plaque area, lipid and collagen content of brachiocephalic artery plaques were measured by histopathological analyses, and the macrophage apoptosis was measured by TUNEL. Correlation of STAMP2/Akt signaling pathway and macrophage apoptosis was validated by Ad-STAMP2 transfection and STAMP2 siRNA inhibition. The diabetic mice showed typical features of IR, hyperglycaemia. Overexpression of STAMP2 ameliorated IR and decreased serum glucose level. In brachiocephalic lesions, lipid content, macrophage quantity and the vulnerability index were significantly decreased by overexpression of STAMP2. Moreover, the numbers of apoptotic cells and macrophages in lesions were both significantly decreased. In vitro, both mRNA and protein expressions of STAMP2 were increased under high glucose treatment. P-Akt was highly expressed and caspase-3 was decreased after overexpression of STAMP2. However, expression of p-Akt protein was decreased and caspase-3 was increased when STAMP2 was inhibited by siRNA. STAMP2 overexpression could exert a protective effect on diabetic atherosclerosis by reducing IR and diminishing macrophage apoptosis.
Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, China.
Jia
J
Wang
Lu
L
Han
Zhi-hao
ZH
Wang
Wen-yuan
WY
Ding
Yuan-yuan
YY
Shang
Meng-xiong
MX
Tang
Wen-bo
WB
Li
Yun
Y
Zhang
Wei
W
Zhang
Ming
M
Zhong
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D059305:Diet, High-Fat; D005786:Gene Expression Regulation; D007333:Insulin Resistance / Q000235:genetics; D008264:Macrophages / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D051058:Oncogene Protein v-akt / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction / Q000235:genetics
D008565:Membrane Proteins; C436323:Tiarp protein, mouse; D051058:Oncogene Protein v-akt
STAMP2/Akt signalling pathway; Type 2 diabetes mellitus; apoptosis of macrophage; insulin resistance; vascular; vulnerable plaque