Table 3: Clinical studies of AGE-RAGE inhibitory effects of lipid-lowering drugs.
| Therapeutic drug | Experimental design | Patient characteristics and treatment groups | Treatment duration | Major findings | Reference |
| Atorvastatin | RCT | T2DM, hypercholesterolaemia (n = 25) • Diet therapy (n = 31) • 10 mg atorvastatin (n = 62) |
4 weeks | • Atorvastatin significantly reduced AGE level, total cholesterol, LDL and triglycerides compared to diet control. | [77] |
| Atorvastatin | Single-arm | NASH, dyslipidaemia (n = 43) • 10 mg atorvastatin |
12 months | • AGE levels were reduced, NAFLD activity was improved and serum glucose levels remained unchanged. | [79] |
| Atorvastatin | Double-blind RCT | T2DM, hypercholesterolaemia (n = 80) • Placebo (n = 41) • 10-20 mg atorvastatin (n = 39) |
6 months | • Atorvastatin elevated serum esRAGE, but not sRAGE in comparison to placebo. | [80] |
| Atorvastatin | RCT | Acute myocardial infarction (n = 190) • 40 mg atorvastatin as loading dose, followed by 10 mg as maintenance dose prior to PCI (n = 98) • PCI only (n = 92) |
30 days | • Atorvastatin improved left ventricular ejection fraction at 6 months post-infarction. • Atorvastatin lowered angiopoietin-like protein 2 and glyceraldehyde-derived AGEs 2 week post-infarction. |
[96] |
| Atorvastatin Pravastatin |
Single-arm | Hypercholesterolaemia (n = 20) • 20 mg atorvastatin/40 mg pravastatin |
8 weeks | • Both statins reduced urinary 8-iso-PGF2α while only atorvastatin elevated sRAGE. • No significant change in ADMA levels for both statins. |
[78] |
| Atorvastatin Pitavastatin |
Single-arm | Acute coronary syndrome (n = 208) • 4 mg pitavastatin/20 mg atorvastatin |
8-12 months | • Both statins significantly decreased AGE level without changing sRAGE. | [81] |
| Pravastatin Pitavastatin |
Randomised, parallel group study | Angina pectoris, post PCI (n = 91) • 4 mg pitavastatin (n = 46) • 20 mg pravastatin (n = 45) |
8 months | • Both statins did not affect circulating AGE level. • Both statins elevated sRAGE level which was negatively correlated with external elastic membrane volume and plaque volume. |
[97] |
| Simvastatin | RCT | T2DM, asymptomatic carotid artery stenosis (n = 70) • AHA step I diet (n = 35) • AHA step I diet and 40 mg simvastatin (n = 35) |
4 months | • Simvastatin reduced MPO, AGEs, RAGE, p65, COX-2, mPGES-1, MMP-2, MMP-9, lipids, oxLDL, gelatinolytic activity, macrophages, T-lymphocytes and HLA-DR + while increased procollagen 1 and collagen in plaques. | [82] |
8-iso-PGF2α: 8-iso Prostaglandin F2α; ADMA: Asymmetric Dimethylarginine; AGE: Advanced Glycation End Product; AHA: American Heart Association; COX-2: Cyclooxygenase-2; esRAGE: Endogenous Secretory Receptor For Advanced Glycation End Product; LDL: Low Density Lipoprotein; MMP-2: Matrix Metalloproteinase-2; MMP-9: Matrix Metalloproteinase-9; mPGES-1: Membrane-Associated Prostaglandin E2 Synthase-1; MPO: Myeloperoxidase; NAFLD: Non-Alcoholic Fatty Liver Disease; NASH: Non-Alcoholic Steatohepatitis; oxLDL: Oxidised Low Density Lipoprotein; PCI: Percutaneous Coronary Intervention; RAGE: Receptor for Advanced Glycation End Product; RCT: Randomised Controlled Trial; sRAGE: Soluble Receptor for Advanced Glycation End Product; T2DM: Type 2 Diabetes Mellitus.