Periferal Arter Hastalığında FBXW7, MASP1 ve SERP1 mRNA Ekspresyon Seviyelerinin İncelenmesi

Abstract

Amaç: Periferik Arter Hastalığı (PAD) dünya çapında kardiyovasküler morbiditenin üçüncü önde gelen nedenidir. Daha önce çalışılmamış olan “F-Box and WD domain containing 7” (FBXW7), “mannose-binding lectin-associated serine protease 1” (MASP1) ve “stress associated endoplasmic reticulum protein 1” (SERP1) genlerinin PAD hastalığındaki potansiyel rollerini araştırmayı amaçladık. Materyal ve Metot: Toplam 78 periferal arter hastalığı olan birey ve 76 sağlıklı birey çalışmaya dahil edilmiştir. Total RNA kan örneklerinden izole edildi ve FBXW7, MASP1 ve SERP1 mRNA ekspresyonları kantitatif gerçek zamanlı polimeraz zincir reaksiyonu kullanılarak belirlenmiştir. Bulgular: FBXW7, MASP1 ve SERP1 genlerinin ifade düzeyleri periferik arter hastalığı olan hastalar ile sağlıklı bireyler arasında istatistiksel olarak farklılık göstermemiştir (p>0,05). Sonuç: FBXW7, MASP1 ve SERP1 proteinlerinin arterle ilişkisi olmasına rağmen periferik arter hastalığının gelişiminde etkili değildirler.

Keywords

• FBXW7 geni
• MASP1 geni
• mRNA ekspresyonu
• Periferik arter hastalığı
• SERP1 geni

Investigation of FBXW7, MASP1 and SERP1 mRNA Expression Levels in Patients with Peripheral Artery Disease

Abstract

Objective: Peripheral Artery Disease (PAD) is the third leading cause of cardiovascular morbidity worldwide. Given their established roles in lipid metabolism, the lectin-complement pathway, and endoplasmic reticulum stress, we aimed to investigate the potential involvement of the FBXW7, MASP1, and SERP1 genes in PAD. This study sought to evaluate whether these genes could serve as non-invasive biomarkers for the diagnosis of PAD, as they have not been previously explored in this patient population. Materials and Methods: A total of 78 individuals with peripheral arterial disease and 76 healthy individuals were included in the study. Total RNA was extracted from blood samples, and the expressions of FBXW7, MASP1, and SERP1 mRNAs were determined using the real-time polymerase chain reaction (rt-PCR). Results: No statistically significant differences were observed in the expression levels of FBXW7, MASP1, and SERP1 genes between PAD patients and healthy subjects (p > 0.05). Conclusion: Although FBXW7, MASP1, and SERP1 proteins are associated with arterial function, they do not appear to play a direct role in the development of peripheral artery disease.

Keywords

• FBXW7 gene
• MASP1 gene
• mRNA expression
• Peripheral artery disease
• SERP1 gene

References

1. 1. SHI Y, XU X, LUAN P, et al. miR-124-3p regulates angiogenesis in peripheral arterial disease by targeting STAT3. Mol Med Rep. 2020;22(6):4890-4898.
2. 2. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015;116(9):1509-1526.
3. 3. Stojkovic S, Jurisic M, Kopp CW, et al. Circulating microRNAs identify patients at increased risk of in-stent restenosis after peripheral angioplasty with stent implantation. Atherosclerosis. 2018;269:197-203.
4. 4. Hiatt WR, Armstrong EJ, Larson CJ, Brass EP. Pathogenesis of the limb manifestations and exercise limitations in peripheral artery disease. Circ Res. 2015;116(9):1527-1539.
5. 5. Firnhaber JM, Powell CS. Lower extremity peripheral artery disease: Diagnosis and treatment. Am Fam Physician. 2019;99(6):362-369.
6. 6. Fowkes FGR, Aboyans V, Fowkes FJI, McDermott MM, Sampson UKA, Criqui MH. Peripheral artery disease: Epidemiology and global perspectives. Nat Rev Cardiol. 2017;14(3):156-170.
7. 7. Bauersachs R, Zeymer U, Brière JB, Marre C, Bowrin K, Huelsebeck M. Burden of coronary artery disease and peripheral artery disease: A literature review. Cardiovasc Ther. 2019;2019:8295054. doi:10.1155/2019/8295054
8. 8. Bengoechea-Alonso MT, Ericsson J. The phosphorylation-dependent regulation of nuclear SREBP1 during mitosis links lipid metabolism and cell growth. Cell Cycle. 2016;15(20):2753-2765.

9. 9. Abudesimu A, Adi D, Siti D, et al. Association of lipid metabolism relevant gene FBXW7 polymorphism with coronary artery disease in Uygur Chinese population in Xinjiang, China: a case-control. Int J Clin Exp Pathol. 2017;10(11):11179-11187
10. 10. Wang H, Zhang C, Zhang C, Wang Y, Zhai K, Tong Z. MicroRNA-122-5p regulates coagulation and inflammation through MASP1 and HO-1 genes. Infection, Genetics and Evolution. 2022;100:105268. doi: 10.1016/j.meegid.2022.105268
11. 11. Krarup A, Gulla KC, Gál P, Hajela K, Sim RB. The action of MBL-associated serine protease 1 (MASP1) on factor XIII and fibrinogen. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics. 2008;1784(9):1294-1300.
12. 12. SERP1 Gene–GeneCards SERP1 Protein SERP1 Antibody. https://www.genecards.org/cgi-bin/carddisp.pl?gene=SERP1. Accessed November 1, 2025.
13. 13. Popescu AI, Rata AL, Barac S, et al. Narrative review of biological markers in chronic limb-threatening ıschemia. Biomedicines. 2024;12(4):798. doi:10.3390/biomedicines12040798
14. 14. Okazaki RA, Rizvi SH, Bretón-Romero R, et al. Novel microRNA pathways of impaired angiogenesis in human peripheral artery disease adipose tissue. Vasc Med. 2025;30(5):537-544.
15. 15. Athavale A, Fukaya E, Leeper NJ. Peripheral artery disease: Molecular mechanisms and novel therapies. Arterioscler Thromb Vasc Biol. 2024;44(6):1165-1170.
16. 16. Gornik HL, Aronow HD, Goodney PP, et al. 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease: A report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. Circulation. 2024;149(24):e1313-e1410.
17. 17. Abudesimu A, Adi D, Siti D, et al. Association of genetic variations in the lipid regulatory pathway genes FBXW7 and SREBPs with coronary artery disease among Han Chinese and Uygur Chinese populations in Xinjiang, China. Oncotarget. 2017;8(50):88199-88210.
18. 18. Zhang L, Yang J, Guo M, Hao M. MiR-223-3p affects myocardial inflammation and apoptosis following myocardial infarction via targeting FBXW7. J Thorac Dis. 2022;14(4):1146-1156.
19. 19. Gao W, Guo N, Zhao S, et al. FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling. Exp Cell Res. 2020;393(1):112059. doi:10.1016/j.yexcr.2020.112059
20. 20. Feng T, Li S, Zhao G, et al. DDX39B facilitates the malignant progression of hepatocellular carcinoma via activation of SREBP1-mediated de novo lipid synthesis. Cellular Oncology. 2023;46(5):1235-1252.
21. 21. Jenny L, Noser D, Larsen JB, et al. MASP-1 of the complement system alters fibrinolytic behaviour of blood clots. Mol Immunol. 2019;114:1-9.
22. 22. Fardipour S, Moein S, Teshnizi SH, Khaytian M, Qujeq D. Evaluation of MASP1, CMPF and U.A serum levels in pre-diabetic subjects in comparison to Normal individuals for early diagnosis of subjects with pre-diabetes, a case-control study. J Diabetes Metab Disord. 2020;19(2):1593-1598. doi:10.1007/s40200-020-00697-9
23. 23. Demeter F, Németh Z, Kajdácsi E, et al. Detrimental interactions of hypoxia and complement MASP-1 in endothelial cells as a model for atherosclerosis-related diseases. Scientific Reports. 2024;14(1):1-16. doi:10.1038/s41598-024-64479-6
24. 24. Kietsiriroje N, Scott GE, Ajjan RA, Brôz J, Schroeder V, Campbell MD. Plasma levels of mannan-binding lectin-associated serine proteases are increased in type 1 diabetes patients with insulin resistance. Clin Exp Immunol. 2024;215(1):58-64.
25. 25. Zhang S, Yang L, Guo S, et al. Mannose binding lectin-associated serine protease-1 is a novel contributor to myocardial ischemia/reperfusion injury. Int J Cardiol. 2023;389:131193. doi: 10.1016/j.ijcard.2023.131193
26. 26. Cai J, Sun Z, Zhang L, Xu H. SERP1 reduces inchoate acute hepatic injury through regulation of endoplasmic reticulum stress via the GSK3β/β‑catenin/TCF/LEF signaling pathway. Mol Med Rep. 2022;25(6):193. doi:10.3892/mmr.2022.12709
27. 27. You T, Zhang B. CircWDR33 alleviates human pulmonary microvascular endothelial cell injury in sepsis-associated acute lung injury by targeting miR-217-5p/SERP1 axis. Int Immunopharmacol. 2022;113(Pt B):109440. doi:10.1016/j.intimp.2022.109440
28. 28. Gao M, Yu T, Liu D, et al. Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1. Clin Sci (Lond). 2021;135(2):347-365
29. 29. Fatima S, Ambreen S, Mathew A, et al. ER-stress and senescence coordinately promote endothelial barrier dysfunction in diabetes-induced atherosclerosis. Nutrients. 2022;14(14):2786. doi:10.3390/nu1414278