PMID- 36830898
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230228
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 11
IP  - 2
DP  - 2023 Jan 26
TI  - Lower Extremity Arterial Disease in Type 2 Diabetes Mellitus: Metformin Inhibits 
      Femoral Artery Ultrastructural Alterations as well as Vascular Tissue Levels of 
      AGEs/ET-1 Axis-Mediated Inflammation and Modulation of Vascular iNOS and eNOS 
      Expression.
LID - 10.3390/biomedicines11020361 [doi]
LID - 361
AB  - Lower extremity arterial disease (LEAD) is a major risk factor for amputation in 
      diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 
      (ET-1)/nitric oxide synthase (NOS) axis-mediated femoral artery injury with and 
      without metformin has not been previously investigated. Type 2 diabetes mellitus 
      (T2DM) was established in rats, with another group of rats treated for two weeks 
      with 200 mg/kg metformin, before being induced with T2DM. The latter cohort were 
      continued on metformin until they were sacrificed at week 12. Femoral artery 
      injury was established in the diabetic group as demonstrated by substantial 
      alterations to the femoral artery ultrastructure, which importantly were 
      ameliorated by metformin. In addition, diabetes caused a significant (p < 0.0001) 
      upregulation of vascular tissue levels of AGEs, ET-1, and iNOS, as well as high 
      blood levels of glycated haemoglobin, TNF-alpha, and dyslipidemia. All of these 
      parameters were also significantly inhibited by metformin. Moreover, metformin 
      treatment augmented arterial eNOS expression which had been inhibited by diabetes 
      progression. Furthermore, a significant correlation was observed between femoral 
      artery endothelial tissue damage and glycemia, AGEs, ET-1, TNF-alpha, and 
      dyslipidemia. Thus, in a rat model of T2DM-induced LEAD, an association between 
      femoral artery tissue damage and the AGEs/ET-1/inflammation/NOS/dyslipidemia axis 
      was demonstrated, with metformin treatment demonstrating beneficial vascular 
      protective effects.
FAU - Shati, Ayed A
AU  - Shati AA
AUID- ORCID: 0000-0003-0444-5595
AD  - Department of Child Health, College of Medicine, King Khalid University, Abha 
      61421, Saudi Arabia.
FAU - Maarouf, Amro
AU  - Maarouf A
AD  - Department of Clinical Biochemistry, Birmingham Heartlands Hospital, University 
      Hospitals Birmingham NHS Foundation Trust, Birmingham B9 5SS, UK.
FAU - Dawood, Amal F
AU  - Dawood AF
AUID- ORCID: 0000-0001-7646-0909
AD  - Department of Basic Medical Sciences, College of Medicine, Princess Nourah Bint 
      Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
FAU - Bayoumy, Nervana M
AU  - Bayoumy NM
AD  - Department of Physiology, College of Medicine, King Saud University, Riyadh 
      11461, Saudi Arabia.
FAU - Alqahtani, Youssef A
AU  - Alqahtani YA
AD  - Department of Child Health, College of Medicine, King Khalid University, Abha 
      61421, Saudi Arabia.
FAU - A Eid, Refaat
AU  - A Eid R
AUID- ORCID: 0000-0001-5633-9562
AD  - Department of Pathology, College of Medicine, King Khalid University, Abha 61421, 
      Saudi Arabia.
FAU - Alqahtani, Saeed M
AU  - Alqahtani SM
AD  - Department of Surgery, College of Medicine, King Khalid University, Abha 61421, 
      Saudi Arabia.
FAU - Abd Ellatif, Mohamed
AU  - Abd Ellatif M
AD  - Department of Clinical Biochemistry, College of Medicine, King Khalid University, 
      Abha 61421, Saudi Arabia.
AD  - Department of Medical Biochemistry, College of Medicine, Mansoura University, 
      Mansoura 35516, Egypt.
FAU - Al-Ani, Bahjat
AU  - Al-Ani B
AD  - Department of Physiology, College of Medicine, King Khalid University, Abha 
      61421, Saudi Arabia.
FAU - Albawardi, Alia
AU  - Albawardi A
AUID- ORCID: 0000-0002-0815-3891
AD  - Department of Pathology, College of Medicine and Health Sciences, United Arab 
      Emirates University, Al Ain 15551, United Arab Emirates.
LA  - eng
GR  - Researchers Supporting Project number (PNURSP2023R110)/Princess Nourah bint 
      Abdulrahman University/
PT  - Journal Article
DEP - 20230126
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC9953164
OTO - NOTNLM
OT  - AGEs
OT  - ET-1
OT  - NOS
OT  - diabetes
OT  - dyslipidemia
OT  - femoral artery
OT  - inflammation
OT  - metformin
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/26 06:00
MHDA- 2023/02/26 06:01
PMCR- 2023/01/26
CRDT- 2023/02/25 01:27
PHST- 2022/12/27 00:00 [received]
PHST- 2023/01/24 00:00 [revised]
PHST- 2023/01/25 00:00 [accepted]
PHST- 2023/02/25 01:27 [entrez]
PHST- 2023/02/26 06:00 [pubmed]
PHST- 2023/02/26 06:01 [medline]
PHST- 2023/01/26 00:00 [pmc-release]
AID - biomedicines11020361 [pii]
AID - biomedicines-11-00361 [pii]
AID - 10.3390/biomedicines11020361 [doi]
PST - epublish
SO  - Biomedicines. 2023 Jan 26;11(2):361. doi: 10.3390/biomedicines11020361.