PMID- 35625721
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230308
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 10
IP  - 5
DP  - 2022 Apr 23
TI  - Metformin Protects against Diabetic Cardiomyopathy: An Association between 
      Desmin-Sarcomere Injury and the iNOS/mTOR/TIMP-1 Fibrosis Axis.
LID - 10.3390/biomedicines10050984 [doi]
LID - 984
AB  - The intermediate filament protein desmin is essential for maintaining the 
      structural integrity of sarcomeres, the fundamental unit of cardiac muscle. 
      Diabetes mellitus (DM) can cause desmin to become dysregulated, following 
      episodes of nitrosative stress, through the activation of the iNOS/mTOR/TIMP-1 
      pathway, thereby stimulating collagen deposition in the myocardium. In this 
      study, type 2 diabetes mellitus (T2DM) was induced in rats. One group of animals 
      was pre-treated with metformin (200 mg/kg) prior to diabetes induction and 
      subsequently kept on metformin until sacrifice at week 12. Cardiac injuries 
      developed in the diabetic rats as demonstrated by a significant (p < 0.0001) 
      inhibition of desmin immunostaining, profound sarcomere ultrastructural 
      alterations, substantial damage to the left ventricular tissue, collagen 
      deposition, and abnormal ECG recordings. DM also significantly induced the 
      cardiac expression of inducible nitric oxide synthase (iNOS), mammalian target of 
      rapamycin (mTOR), and the profibrogenic biomarker tissue inhibitor of 
      metalloproteinase-1 (TIMP-1). The expression of all these markers was 
      significantly inhibited by metformin. In addition, a significant (p < 0.0001) 
      correlation between desmin tissue levels/sarcomere damage and glycated 
      hemoglobin, heart rate, iNOS, mTOR, and fibrosis was observed. These findings 
      demonstrate an association between damage of the cardiac contractile unit-desmin 
      and sarcomere-and the iNOS/mTOR/TIMP-1/collagen axis of fibrosis in T2DM-induced 
      cardiomyopathy, with metformin exhibiting beneficial cardiovascular pleiotropic 
      effects.
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, Riyadh 11671, Saudi Arabia.
AD  - Department of Physiology, Kasr al-Aini Faculty of Medicine, Cairo University, 
      Cairo 12613, Egypt.
FAU - Alzamil, Norah M
AU  - Alzamil NM
AD  - Department of Clinical Science, Family Medicine, College of Medicine, Princess 
      Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
FAU - Hewett, Peter W
AU  - Hewett PW
AD  - Institute of Cardiovascular Sciences, College of Medicine and Dental Sciences, 
      University of Birmingham, Birmingham B15 2TT, UK.
FAU - Momenah, Maha A
AU  - Momenah MA
AUID- ORCID: 0000-0002-1827-0995
AD  - Department of Biology, College of Science, Princess Nourah Bint Abdulrahman 
      University, Riyadh 11671, Saudi Arabia.
FAU - Dallak, Mohammad
AU  - Dallak M
AD  - Department of Physiology, College of Medicine, King Khalid University, Abha 
      61421, Saudi Arabia.
FAU - Kamar, Samaa S
AU  - Kamar SS
AUID- ORCID: 0000-0002-9040-584X
AD  - Department of Medical Histology, Kasr al-Aini Faculty of Medicine, Cairo 
      University, Cairo 12613, Egypt.
FAU - Abdel Kader, Dina H
AU  - Abdel Kader DH
AD  - Department of Medical Histology, Kasr al-Aini Faculty of Medicine, Cairo 
      University, Cairo 12613, Egypt.
FAU - Yassin, Hanaa
AU  - Yassin H
AD  - Department of Physiology, Kasr al-Aini Faculty of Medicine, Cairo University, 
      Cairo 12613, Egypt.
FAU - Haidara, Mohamed A
AU  - Haidara MA
AD  - Department of Physiology, Kasr al-Aini Faculty of Medicine, Cairo University, 
      Cairo 12613, Egypt.
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 - Al-Ani, Bahjat
AU  - Al-Ani B
AD  - Department of Physiology, College of Medicine, King Khalid University, Abha 
      61421, Saudi Arabia.
LA  - eng
GR  - Princess Nourah bint Abdulrahman University, through the Research Funding 
      Program, grant No (G18-00006)./King Abdul Aziz University Hospital/
PT  - Journal Article
DEP - 20220423
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC9139128
OTO - NOTNLM
OT  - cardiomyopathy
OT  - desmin
OT  - diabetes
OT  - fibrosis
OT  - metformin
OT  - sarcomere
COIS- The authors declare no conflict of interest.
EDAT- 2022/05/29 06:00
MHDA- 2022/05/29 06:01
PMCR- 2022/04/23
CRDT- 2022/05/28 01:07
PHST- 2022/03/07 00:00 [received]
PHST- 2022/04/09 00:00 [revised]
PHST- 2022/04/20 00:00 [accepted]
PHST- 2022/05/28 01:07 [entrez]
PHST- 2022/05/29 06:00 [pubmed]
PHST- 2022/05/29 06:01 [medline]
PHST- 2022/04/23 00:00 [pmc-release]
AID - biomedicines10050984 [pii]
AID - biomedicines-10-00984 [pii]
AID - 10.3390/biomedicines10050984 [doi]
PST - epublish
SO  - Biomedicines. 2022 Apr 23;10(5):984. doi: 10.3390/biomedicines10050984.