Fatty acid amide hydrolase is a key regulator of the endocannabinoid‐induced myocardial tissue injury

  title={Fatty acid amide hydrolase is a key regulator of the endocannabinoid‐induced myocardial tissue injury},
  author={Bėla Horv{\'a}th and Partha Mukhopadhyay and Mohanraj Rajesh and Shingo Matsumoto and Keita Saito and Sandor Batkai and Yue R Gao and Benjamin F. Cravatt and György Haskó and P{\'a}l Pacher},
  journal={The FASEB Journal},
Activation of the endocannabinoid system mediates cardiac hypertrophy induced by rosiglitazone.
It is found that activation of PPARγ by RSG stimulated the endocannabinoid system (ECS), a membrane lipid signaling system, which induced cardiac hypertrophy, and that the AEA/CB1/mTOR axis mediates RSG-induced cardiac remodeling.
Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice.
Modulation of the Oxidative Stress and Lipid Peroxidation by Endocannabinoids and Their Lipid Analogues
A better understanding of the main mechanisms triggered by the cross-talk between the oxidative stress and the ECS is provided, focusing also on the enzymatic and non-enzymatic antioxidants as scavengers of reactive aldehydes and their toxic bioactive adducts.
Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis
Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death, and the above-described effects on mitochondrial function and biogenesis may contribute to its beneficial properties described in numerous other models of tissue injury.
Cannabinoid 1 Receptor Promotes Cardiac Dysfunction, Oxidative Stress, Inflammation, and Fibrosis in Diabetic Cardiomyopathy
Activation of CB1 receptors by endocannabinoids may play an important role in the pathogenesis of diabetic cardiomyopathy by facilitating MAPK activation, AT1R expression/signaling, AGE accumulation, oxidative/nitrative stress, inflammation, and fibrosis.
Effects of activation of endocannabinoid system on myocardial metabolism.
Endocannabinoids exert their effect on the regulation of energy homeostasis via activation of specific receptors. They control food intake, secretion of insulin, lipids and glucose metabolism, lipid
Role of cannabinoids and the endocannabinoid system in modulation of diabetic cardiomyopathy
A better understanding of the role of cannabinoids and the endocannabinoid system in diabetic cardiomyopathy may provide novel strategies to manipulate such a serious diabetic complication.
Fatty Acid Amide Hydrolase Deficiency Enhances Intraplaque Neutrophil Recruitment in Atherosclerotic Mice
Increased anandamide and related FAAH substrate levels are associated with the development of smaller atherosclerotic plaques with high neutrophil content, accompanied by an increased proinflammatory immune response.


The emerging role of the endocannabinoid system in cardiovascular disease
The therapeutic potential of the modulation of the ECS by selective agonists/antagonists in various cardiovascular disorders associated with inflammation and tissue injury, ranging from myocardial infarction and heart failure to atherosclerosis and cardiometabolic disorders is discussed.
Fatty Acid Amide Hydrolase Determines Anandamide-induced Cell Death in the Liver*
The endocannabinoid anandamide (AEA) induces cell death in many cell types, but determinants of AEA-induced cell death remain unknown. In this study, we investigated the role of the AEA-degrading
Cannabinoid CB1 receptor antagonists for atherosclerosis and cardiometabolic disorders: new hopes, old concerns?
  • P. Pacher
  • Biology, Medicine
    Arteriosclerosis, thrombosis, and vascular biology
  • 2009
The dysregulation of the endocannabinoid system has recently been implicated in numerous human diseases, and its pharmacological modulation is a very promising strategy to treat various inflammatory, neurodegenerative, cardiovascular, metabolic disorders, ischemia/reperfusion damage, as well as cancer and pain.
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
A comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy is provided.
Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease.
This review focuses on the human data available on the pathophysiological relevance of the peroxynitrite-PARP pathway in a wide range of disparate diseases, ranging from myocardial ischemia/reperfusion injury, myocarditis, heart failure, circulatory shock, and diabetic complications to atherosclerosis, arthritis, colitis, and neurodegenerative disorders.
Potent Metalloporphyrin Peroxynitrite Decomposition Catalyst Protects Against the Development of Doxorubicin-Induced Cardiac Dysfunction
Peroxynitrite plays a key role in the pathogenesis of DOX-induced cardiac failure and may represent a new cardioprotective strategy after DOX exposure or in other conditions associated with peroxynite formation, including myocardial ischemia/reperfusion injury.
Modulation of the endocannabinoid system in cardiovascular disease: therapeutic potential and limitations.
In the absence of a cellular storage mechanism for endocannabinoids, their tissue levels are determined by the balance between the rate of their “on-demand” synthesis and their enzymatic degradation.
CB1 cannabinoid receptors promote oxidative stress and cell death in murine models of doxorubicin-induced cardiomyopathy and in human cardiomyocytes.
CB1 activation in cardiomyocytes may amplify the reactive oxygen/nitrogen species-MAPK activation-cell death pathway in pathological conditions when the endocannabinoid synthetic or metabolic pathways are dysregulated by excessive inflammation and/or oxidative/nitrosative stress, which may contribute to the pathophysiology of various cardiovascular diseases.
Pharmacological inhibition of CB1 cannabinoid receptor protects against doxorubicin-induced cardiotoxicity.