6533b827fe1ef96bd1286675

RESEARCH PRODUCT

The AMP-Activated Protein Kinase Plays a Role in Antioxidant Defense and Regulation of Vascular Inflammation

Swenja Kröller-schönThomas JansenMiroslava KvandovaThomas MünzelEberhard SchulzPaul StammAndreas DaiberKatie Frenis

subject

0301 basic medicinehypertensionEndotheliumPhysiologyClinical BiochemistryInflammationContext (language use)ReviewPharmacologymedicine.disease_causeBiochemistryendothelial dysfunction03 medical and health sciences0302 clinical medicineAMP-activated protein kinasevascular inflammationoxidative stressMedicineEndothelial dysfunctionProtein kinase AMolecular BiologyAMP-activated protein kinasebiologybusiness.industrylcsh:RM1-950AMPKCell Biologymedicine.diseaselcsh:Therapeutics. Pharmacology030104 developmental biologymedicine.anatomical_structure030220 oncology & carcinogenesisbiology.proteinmedicine.symptombusinessOxidative stress

description

Cardiovascular diseases represent the leading cause of global deaths and life years spent with a severe disability. Endothelial dysfunction and vascular oxidative stress are early precursors of atherosclerotic processes in the vascular wall, all of which are hallmarks in the development of cardiovascular diseases and predictors of future cardiovascular events. There is growing evidence that inflammatory processes represent a major trigger for endothelial dysfunction, vascular oxidative stress and atherosclerosis and clinical data identified inflammation as a cardiovascular risk factor on its own. AMP-activated protein kinase (AMPK) is a central enzyme of cellular energy balance and metabolism that has been shown to confer cardio-protection and antioxidant defense which thereby contributes to vascular health. Interestingly, AMPK is also redox-regulated itself. We have previously shown that AMPK largely contributes to a healthy endothelium, confers potent antioxidant effects and prevents arterial hypertension. Recently, we provided deep mechanistic insights into the role of AMPK in cardiovascular protection and redox homeostasis by studies on arterial hypertension in endothelial and myelomonocytic cell-specific AMPK knockout (Cadh5CrexAMPKfl/fl and LysMCrexAMPKfl/fl) mice. Using these cell-specific knockout mice, we revealed the potent anti-inflammatory properties of AMPK representing the molecular basis of the antihypertensive effects of AMPK. Here, we discuss our own findings in the context of literature data with respect to the anti-inflammatory and antioxidant effects of AMPK in the specific setting of arterial hypertension as well as cardiovascular diseases in general.

https://doi.org/10.3390/antiox9060525