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).