Post-infarct sleep disruption and its relation to cardiac remodeling in a rat model of myocardial infarction.
Sleep disruption after myocardial infarction (MI) by affecting ubiquitin-proteasome system (UPS) is thought to contribute to myocardial remodeling and progressive worsening of cardiac function. The aim of current study was to test the hypothesis about the increased risk of developing heart failure due to experience of sleep restriction (SR) after MI. Male Wistar rats (n = 40) were randomly assigned to four experimental groups: (1) Sham, (2) MI, (3) MI and SR (MI + SR) (4) Sham and SR (Sham + SR). MI was induced by permanent ligation of left anterior descending coronary artery. Twenty-four hours after surgery, animals were subjected to chronic SR paradigm. Blood sampling was performed at days 1, 8 and 21 after MI for determination of serum levels of creatine kinase-MB (CK-MB), corticosterone, malondialdehyde (MDA) and nitric oxide (NO). Finally, at 21 days after MI, echocardiographic parameters and expression of MuRF1, MaFBx, A20, eNOS, iNOS and NF-kB in the heart were evaluated. We used H&E staining to detect myocardial hypertrophy. We found out that post infarct SR increased corticosterone levels. Our results highlighted deteriorating effects of post-MI SR on NO production, oxidative stress, and echocardiographic indexes (p < 0.05). Moreover, its detrimental effects on myocardial damage were confirmed by overexpression of MuRF1, MaFBx, iNOS and NF-kB (p < 0.001) in left ventricle and downregulation of A20 and eNOS (p < 0.05). Furthermore, histological examination revealed that experience of SR after MI increased myocardial diameter as compared to Sham subjects (p < 0.05). Our data suggest that SR after MI leads to an enlargement of the heart within 21 days, marked by an increase in oxidative stress and NO production as well as an imbalance in UPS that ultimately results in cardiac dysfunction and heart failure.
a Physiology Department , Faculty of Medicine, Tehran University of Medical Sciences , Tehran , Iran.
Marjan
M
Aghajani
a Physiology Department , Faculty of Medicine, Tehran University of Medical Sciences , Tehran , Iran.
Mahdieh
M
Faghihi
a Physiology Department , Faculty of Medicine, Tehran University of Medical Sciences , Tehran , Iran.|b Occupational Sleep Research Center, Tehran University of Medical Sciences , Tehran , Iran.
Alireza
A
Imani
c Traditional Medicine Clinical Trial Research Center, Shahed University , Tehran , Iran.|d Department of Physiology , Medical Faculty, Shahed University , Tehran , Iran.
Mohammad Reza
MR
Vaez Mahdavi
e Genetic Department , Faculty of Medicine, Tehran University of Medical Sciences , Tehran , Iran.
Abbas
A
Shakoori
f Anatomy Department , Faculty of Medicine, Tehran University of Medical Sciences , Tehran , Iran.
Tayebeh
T
Rastegar
a Physiology Department , Faculty of Medicine, Tehran University of Medical Sciences , Tehran , Iran.
Hoda
H
Parsa
e Genetic Department , Faculty of Medicine, Tehran University of Medical Sciences , Tehran , Iran.
Saman
S
Mehrabi
a Physiology Department , Faculty of Medicine, Tehran University of Medical Sciences , Tehran , Iran.
Fatemeh
F
Moradi
g Shiraz Burn and Wound Healing Research Center, Amir-al-momenin Burn Hospital, Shiraz University of Medical Sciences , Iran.|h Department of Microbiology , Medical Faculty, Shahed University , Tehran , Iran.
Ehsan
E
Kazemi Moghaddam
D000818:Animals; D001835:Body Weight; D003345:Corticosterone; D004452:Echocardiography; D015971:Gene Expression Regulation, Enzymologic; D006321:Heart / Q000033:anatomy & histology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000502:physiology*; D020257:Ventricular Remodeling
D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D003345:Corticosterone
cardiac remodeling; myocardial infarction; nitric oxide; sleep restriction; ubiquitin–proteasome system