Research Article
BibTex RIS Cite

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

Year 2026, Volume: 11 Issue: 1, 16 - 23, 15.03.2026
https://doi.org/10.26453/otjhs.1812461
https://izlik.org/JA52WF29UH

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.

Ethical Statement

Çalışma için etik onay, XXX Yüksek Uzmanlık Eğitim ve Araştırma Hastanesi Klinik Araştırma Etik Kurulu'ndan alınmıştır (Tarih: 20.12.2018, karar no: 2018/7/72). Çalışma, Helsinki Bildirgesi'ne uygun olarak yürütülmüştür.

Supporting Institution

Proje, Türkiye Sağlık Bilimleri Üniversitesi, Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir (proje no: 2019/035).

References

  • 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. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015;116(9):1509-1526.
  • 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. 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. Firnhaber JM, Powell CS. Lower extremity peripheral artery disease: Diagnosis and treatment. Am Fam Physician. 2019;99(6):362-369.
  • 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. 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. 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. 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. 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. 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. SERP1 Gene–GeneCards SERP1 Protein SERP1 Antibody. https://www.genecards.org/cgi-bin/carddisp.pl?gene=SERP1. Accessed November 1, 2025.
  • 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. 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. Athavale A, Fukaya E, Leeper NJ. Peripheral artery disease: Molecular mechanisms and novel therapies. Arterioscler Thromb Vasc Biol. 2024;44(6):1165-1170.
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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

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

Year 2026, Volume: 11 Issue: 1, 16 - 23, 15.03.2026
https://doi.org/10.26453/otjhs.1812461
https://izlik.org/JA52WF29UH

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.

Ethical Statement

Ethical approval for the study was obtained from the XXX High Specialization Education and Research Hospital, Clinical Research Ethics Committee (Date: 20.12.2018, decision no: 2018/7/72). The study was conducted in accordance with the Declaration of Helsinki.

Supporting Institution

The project was supported by the University of Health Sciences Türkiye, Unit of Scientific Research Projects (project no: 2019/035).

References

  • 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. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015;116(9):1509-1526.
  • 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. 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. Firnhaber JM, Powell CS. Lower extremity peripheral artery disease: Diagnosis and treatment. Am Fam Physician. 2019;99(6):362-369.
  • 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. 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. 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. 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. 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. 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. SERP1 Gene–GeneCards SERP1 Protein SERP1 Antibody. https://www.genecards.org/cgi-bin/carddisp.pl?gene=SERP1. Accessed November 1, 2025.
  • 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. 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. Athavale A, Fukaya E, Leeper NJ. Peripheral artery disease: Molecular mechanisms and novel therapies. Arterioscler Thromb Vasc Biol. 2024;44(6):1165-1170.
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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
There are 29 citations in total.

Details

Primary Language English
Subjects Cardiovascular Surgery
Journal Section Research Article
Authors

Bekir Erdoğan 0000-0001-9637-3837

Sibel Kuraş 0000-0002-1230-7777

Fatih Yıılmaz 0000-0002-8439-0426

Fatih Hacımustafaoğlu 0000-0002-1429-0526

Mahmud Esad Pençe 0000-0002-8411-3138

Halime Hanim Pence 0000-0002-8346-1018

Submission Date October 30, 2025
Acceptance Date February 9, 2026
Publication Date March 15, 2026
DOI https://doi.org/10.26453/otjhs.1812461
IZ https://izlik.org/JA52WF29UH
Published in Issue Year 2026 Volume: 11 Issue: 1

Cite

AMA 1.Erdoğan B, Kuraş S, Yıılmaz F, Hacımustafaoğlu F, Pençe ME, Pence HH. Investigation of FBXW7, MASP1 and SERP1 mRNA Expression Levels in Patients with Peripheral Artery Disease. OTJHS. 2026;11(1):16-23. doi:10.26453/otjhs.1812461

Creative Commons License

Online Türk Sağlık Bilimleri Dergisi [Online Turkish Journal of Health Sciences (OTJHS)] is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open-access journal distributed under the terms of the Creative Commons Attribution License (CC BY-NC 4.0). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Click here to get help about article submission processes and "Copyright Transfer Form".