Glycation and HMG-CoA Reductase Inhibitors: Implication in Diabetes and Associated Complications

摘要

CIntroduction: Diabetes Mellitus (DM) acts as an absolute mediator of cardiovascular risk,prompting the prolonged occurrence, size and intricacy of atherosclerotic plaques via enhanced AdvancedGlycation Endproducts (AGEs) formation. Moreover, hyperglycemia is associated with enhancedglyco-oxidized and oxidized Low-Density Lipoprotein (LDL) possessing greater atherogenicityand decreased the ability to regulate HMG-CoA reductase (HMG-R). Although aminoguanidine (AG)prevents the AGE-induced protein cross-linking due to its anti-glycation potential, it exerts several unusualpharmaco-toxicological effects thus restraining its desirable therapeutic effects. HMG-R inhibitors/statins exhibit a variety of beneficial impacts in addition to the cholesterol-lowering effects.Objective: Inhibition of AGEs interaction with receptor for AGEs (RAGE) and glyco-oxidized-LDL byHMG-R inhibitors could decrease LDL uptake by LDL-receptor (LDL-R), regulate cholesterol synthesisvia HMG-R, decrease oxidative and inflammatory stress to improve the diabetes-associatedcomplications.Conclusion: Current article appraises the pathological AGE-RAGE concerns in diabetes and its associatedcomplications, mainly focusing on the phenomenon of both circulatory AGEs and those accumulatingin tissues in diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy, discussing thepotential protective role of HMG-R inhibitors against diabetic complications.