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. 2016 Apr 25;27(4):408–413. doi: 10.1097/MOL.0000000000000314

Table 1.

The effects of melatonin on various cardiovascular diseases

Function Factor/pathway/action References
Melatonin and myocardial ischemia-reperfusion injury
 Induce/activate SIRT1 [21,22,28]
NOTCH1, NICD, HES1, p-Akt/Akt ratio [24]
BCL-2, [22,24]
SOD-1, HFG [23]
Adiponectin, ERK42/44, GSK-3β, STAT-3, PKB/Akt [27]
TLR4, STAT3, SAFE [30]
 Reduce/inhibit CK-MB [19]
BAX [21,22]
Ac-FoxO1, Ac-p53, Ac-NF-κB [22]
Caspase, ROS [23]
Caspase-3, PTEN, [24]
Serum insulin, HOMA index [27]
PERK/eIF2α/ATF4 signaling pathway [28]
Melatonin and myocardial chronic intermittent hypoxia injury
 Reduce/inhibit TNF-α, IL-6, COX-2; PC1, TGF-β; P22, NOX2; CAT, MnSOD [32]
CK, LDH, MDA [35]
iNOS/i-mtNOS, nNOS/c-mtNOS [36]
Melatonin and pulmonary hypertension
 Induce/activate Nitric oxide [41]
 Reduce/inhibit RV hypertrophy and dysfunction, interstitial fibrosis [39]
Pulmonary artery pressure and resistance [40]
RV/LV+S, RVSP, HIF-1α, PCNA, NF-κb, ERK1/2, p-Akt [41]
Melatonin and hypertension
 Reduce/inhibit Oxidative load in the LV, aorta and LV hypertrophy, LV fibrosis [44]
Renal oxidative stress and vascular reactivity [45]
Melatonin and vascular diseases
 Reduce/inhibit Number and areas of atheromatous plaques [50]
MLCK, p-MYPT, p-MLC, ERK, p-38 [51]
eNOS [54]
Melatonin and valvular heart disease
 Induce/activate bFGF, BCL-2, PDGF [60]
 Reduce/inhibit Caspase 3, PUMA, BAX [60]
Melatonin and lipid metabolism
 Reduce/inhibit TG, LDL-C [61,63]
FFA [62]
TC, oxidized LDL-C, apoB100 [63]

Ac-FoxO1, acetylated forkhead box protein O1; Ac-p53,acetylated p53; Ac-NF-κB, acetylated nuclear factor kappa-light-chain-enhancer of activated B cells; ATF4, activating transcription factor 4; BCL-2, B-cell lymphoma 2; CAT, catalase; ERK42/44, extracellular signal-regulated kinases 42/44; GSK-3 β, glycogen synthase kinase-3 beta; LDH, lactate dehydrogenase; MnSOD, manganese-superoxide dismutase; p-Akt, phosphorylated protein kinase B; PKB, Protein Kinase B; PERK, protein kinase ribonucleic acid-like endoplasmic reticulum kinase; SIRT1, silent information regulator 1; TNF-α: tumor necrosis factor-α; bFGF, basic fibroblast growth factor; CK-MB, creatine kinase-MB; HIF-1α, hypoxia-inducible factor-1α; NICD, NOTCH1 intracellular domain; PCNA, proliferating cell nuclear antigen; PUMA, p53 upregulated modulator of apoptosis; PDGF, platelet-derived growth factor; RV/LV+S, right ventricle to left ventricle plus intraventricular septum; ROS, reactive oxygen species; SOD-1, superoxide dismutase; STAT-3, signal transducer and activator of transcription 3; TLR4, toll-like receptor 4; TGF-β transforming growth factor β; TG, triglycerides.

A summary of the mechanistic effects of melatonin on myocardial ischemia-reperfusion injury, myocardial hypoxia-reoxygenation injury, pulmonary hypertension, hypertension, and vascular diseases. (original).