تفاصيل الوثيقة

نوع الوثيقة : مقال في مجلة دورية 
عنوان الوثيقة :
Metformin improves the angiogenic potential of human CD34⁺ cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction
Metformin improves the angiogenic potential of human CD34⁺ cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction
 
لغة الوثيقة : الانجليزية 
المستخلص : BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM). To identify the most effective treatment for CVD, it is paramount to understand the mechanism behind cardioprotective therapies. Although metformin has been shown to reduce CVD in Type-2 DM clinical trials, the underlying mechanism remains unexplored. CD34(+) cell-based therapies offer a new treatment approach to CVD. The aim of this study was to investigate the effect of metformin on the angiogenic properties of CD34(+) cells under conditions mimicking acute myocardial infarction in diabetes. METHODS: CD34(+) cells were cultured in 5.5 or 16.5 mmol/L glucose ± 0.01 mmol/L metformin and then additionally ± 4 % hypoxia. The paracrine function of CD34(+) cell-derived conditioned medium was assessed by measuring pro-inflammatory cytokines, vascular endothelial growth factor A (VEGFA), and using an in vitro tube formation assay for angiogenesis. Also, mRNA of CD34(+) cells was assayed by microarray and genes of interest were validated by qRT-PCR. RESULTS: Metformin increased in vitro angiogenesis under hyperglycemia-hypoxia and augmented the expression of VEGFA. It also reduced the angiogenic-inhibitors, chemokine (C-X-C motif) ligand 10 (CXCL10) and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNAs, which were upregulated under hyperglycemia-hypoxia. In addition metformin, increased expression of STEAP family member 4 (STEAP4) under euglycemia, indicating an anti-inflammatory effect. CONCLUSIONS: Metformin has a dual effect by simultaneously increasing VEGFA and reducing CXCL10 and TIMP1 in CD34(+) cells in a model of the diabetic state combined with hypoxia. Therefore, these angiogenic inhibitors are promising therapeutic targets for CVD in diabetic patients. Moreover, our data are commensurate with a vascular protective effect of metformin and add to the understanding of underlying mechanisms 
ردمد : 1475-2840 
اسم الدورية : Cardiovasc Diabetol 
المجلد : 15 
العدد : 1 
سنة النشر : 1437 هـ
2016 م 
نوع المقالة : مقالة علمية 
تاريخ الاضافة على الموقع : Monday, May 2, 2016 

الباحثون

اسم الباحث (عربي)اسم الباحث (انجليزي)نوع الباحثالمرتبة العلميةالبريد الالكتروني
Sherin BakhashabBakhashab, Sherin باحث رئيسي sbakhashab@kau.edu.sa
Fahad W. AhmedAhmed, Fahad W.باحث مشارك fahad.ahmed@newcastle.ac.uk
Hans‑Juergen SchultenSchulten, Hans‑Juergen باحث مشارك hschulten@kau.edu.sa
Ayat BashirBashir, Ayat باحث مشارك ayatbashir@yahoo.co.uk
Sajjad KarimKarim, Sajjad باحث مشارك skarim@kau.edu.sa
Abdulrahman L. Al‑MalkiAl‑Malki, Abdulrahman L.باحث مشارك alalmalki@kau.edu.sa
Mamdooh A. GariGari, Mamdooh A.باحث مشارك mgari@kau.edu.sa
Adel M. AbuzenadahAbuzenadah, Adel M.باحث مشارك aabuzenadah@kau.edu.sa
Adeel G. ChaudharyChaudhary, Adeel G.باحث مشارك chaudhary@kau.edu.sa
Mohammed H. AlqahtaniAlqahtani, Mohammed H.باحث مشارك mhalqahtani@kau.edu.sa
Sahira LaryLary, Sahira باحث مشارك slary@kau.edu.sa
Farid AhmedAhmed, Farid باحث مشارك fahmed1@kau.edu.sa
Jolanta U. WeaverWeaver, Jolanta U.باحث مشارك Jolanta.Weaver@newcastle.ac.uk

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