Methylation of MMP2, TIMP2, MMP9 and TIMP1 in abdominal aortic aneurysm

Abstract

OBJECTIVES: Abdominal aortic aneurysm (AAA) and its complications are among the most serious cardiovascular diseases and its occurrence has risen sharply in recent years. The aim of this pilot study is to explore the relationship between the methylation of matrix metalloproteinases and tissue inhibitors of the metalloproteinases genes' promoter region, and abdominal aortic aneurysm (AAA) through the detection of the methylation status of MMP2, TIMP2, TIMP1, and MMP9 genes in peripheral blood. METHODS: The study included 43 males with verifi ed AAA (case group) and 34 healthy males (control group). The methylation status of the genes' promoter region was detected by methylation-specifi c polymerase chain reaction (MS-PCR). RESULTS: In adominal aortic aneurysm patients, the methylation ratio of MMP2 gene was positive in 9.3 % (4 cases), 2.3 % (1 case) had methylated TIMP2 gene, 7.0 % (3 cases) had methylated TIMP1 gene, while the methylation ratio of MMP9 gene was positive in 93.0 % (40 cases). In the control group, MMP2 gene was found to be methylated in 5.9 % (2 cases), 5.9 % of cases had methylated TIMP2 and TIMP1 genes (2 cases), and MMP9 gene was found to be methylated in 91.2 % (31 cases). CONCLUSION: In our pilot study, we found no association between DNA methylation of gelatinases and their tissue inhibitors, and the development of an abdominal aortic aneurysm (Tab. 2, Fig. 1, Ref. 27).

The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs

“…The position of the AP-1 sequence of TIMP2 is important, as treatment with 12-O-tetradecanoylphorbol-13-acetate only provokes a response within specific AP-1 consensus regions [ 38 ]. Methylation influences TIMP2 gene expression [ 39 , 40 ], as well as TIMP1 [ 41 ] and TIMP3 [ 42 ]. Further, hypermethylation of the TIMP2 promoter causes transcriptional repression of TIMP2 levels in many types of tumors, including lymphoma [ 43 ] and prostate cancer [ 44 ], resulting in tumor metastasis through MMP activation.…”

The role of rs3025058 polymorphism in the development of ischemic stroke in patients with cardiovascular diseases (review)

“…Доказана ассоциация минорного аллеля 5А rs3025058 гена MMP-3 с аневризмой брюшной аорты (ОШ=1,48; 95% ДИ: 1,23-1,78, р=0,00395). В работах [7][8][9] эти результаты подтверждены.…”

Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

“…This opinion is addressed in a recent article, which evaluates the global methylation level in AAA patient-derived peripheral blood mononuclear cells (PBMCs) and compares it with that in PBMCs from normal subjects [ 40 ]. The study conducted by Skorvanova et al revealed no association of AAA development with DNA methylation of gelatinases and their tissue inhibitors (e.g., MMP2, TIMP2, TIMP1, and MMP9) [ 49 ].…”