CB2 receptor-mediated effects of pro-inflammatory macrophages influence survival of cardiomyocytes

Heinemann, Jan C.; Duerr, Georg Daniel; Keppel, Katharina; Breitbach, Martin; Fleischmann, Bernd K.; Zimmer, Andreas; Wehner, Sven; Welz, Armin; Dewald, Oliver

doi:10.1016/j.lfs.2014.11.027

Cited by 21 publications

(9 citation statements)

References 48 publications

(74 reference statements)

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“…To begin with, circulating levels of endocannabinoids were elevated after cardiac injury, such as myocardial infarction in the rat [27] and ischemia/reperfusion in mice [28]. The CB2 receptors were upregulated in ischemic cardiomyocytes [28] and in cardiomyocytes following cultivation under hypoxia [29]. Our group found general induction of CB1 and CB2 receptor gene expression due to experimental myocardial infarction in the rat 6 weeks after operation [30].…”

Section: Endocannabinoids and Cannabinoid Receptors In The Heartmentioning

confidence: 80%

Cannabinoid CB1/CB2 Receptors in the Heart: Expression, Regulation, and Function

Kaschina¹

2016

Cannabinoids in Health and Disease

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Endocannabinoids exert their actions in the heart and vessels, at least in part, by stimulating the cannabinoid CB and the CB receptor subtypes which belong to a group of seven transmembrane-spanning receptors and are coupled to Gi/o-proteins. Activation of cardiovascular CB receptors leads to depressed cardiac contractility and hypotension. Conversely, in most studies, the CB receptor antagonists are cardioprotective against ischemia reperfusion injury, myocardial ischemia, heart failure, and cardiomyopathies. Evidence to date indicates that CB receptor activation is cardioprotective. CB receptor-mediated effects such as anti-inflammation and anti-fibrosis may be in part opposite to the actions of the CB receptor. The aim of this review is to up-date on recent experimental findings and controversies on the role of endocannabinoid system in the myocardial injury with emphasis on pathophysiological processes such as left ventricular remodeling, cardiac fibrosis, hypertrophy, and endothelial dysfunction. Recent experimental studies employing genetic deficiency of CB and CB receptors and endocannabinoid anandamide metabolizing enzymes are reviewed. Moreover, the protective mechanisms which are mediated by cannabinoid receptors during ischemic preconditioning as well as in the early and late phase after myocardial infarction are discussed in the context of possible therapeutic implications.Keywords: cannabinoid receptors, CB , CB , heart, myocardial infarction, heart remodeling . IntroductionEndocannabinoids, its degrading enzymes and the cannabinoid CB and CB receptors are present in rodent and human cardiovascular tissues. In addition to its role in the control of the central nervous system, the endocannabinoid system ECS may play a pivotal part in cardiovascular regulation by heart diseases reviewed in [ -] .In normal physiological conditions, ECS is not highly regulated. However, by cardiovascular pathologies, this system is activated and may reflect a protective response which limits cardiac injury. Activated ECS has been implicated in acute cardiovascular conditions such as hemorrhagic, septic, and cardiogenic shock as well as in chronic diseases such as coronary heart disease, heart failure, and cardiomyopathy.Endocannabinoids exert their actions in the heart and vessels, at least in part, by stimulating the cannabinoid CB and the CB receptor subtypes which belong to a group of seven transmembrane-spanning receptors and are coupled to Gi/o-proteins [ , ]. Signaling through the CB receptor elicits hypotension, bradycardia, and negative inotropy [ ]. Moreover, this receptor subtype is implicated in inflammation, apoptosis, oxidative stress [ ], and metabolic dysregulation [ ], thereby contributing to tissue injury. The CB receptors, on the contrary, may play a compensatory anti-inflammatory, anti-oxidative, and anti-atherogenic role [ , ] contributing to cardiovascular protection.Nevertheless, the role of cannabinoid receptors in the heart under several pathological conditions remains controversial. ...

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Section: Endocannabinoids and Cannabinoid Receptors In The Heartmentioning

confidence: 80%

Cannabinoid CB1/CB2 Receptors in the Heart: Expression, Regulation, and Function

Kaschina¹

2016

Cannabinoids in Health and Disease

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“…Stokke et al (20) rightfully concluded that strain imaging probably better reflects systolic function in patients with a preserved estimated LVEF (20)(21)(22)(23)(24). Long-axis function might be a potential indicator of subclinical LV dysfunction in numerous diseases (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Speckle Tracking Strain Assessment of Left Ventricle in Synthetic Cannabinoid and Heroin Users

Demirkıran¹

2018

Anatol J Cardiol

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ObjectiveThere is growing evidence regarding the numerous adverse effects of synthetic cannabinoids (SCBs) on the cardiovascular system; however, no studies have shown the cardiovascular effects of opioids using strain echocardiography. This study examines the cardiac structure and function using echocardiographic strain imaging in heroin and synthetic cannabinoid users.MethodsThis double-blind study included patients who were admitted or referred to a rehabilitation center for heroin (n=31) and synthetic cannabinoid users (n=30). Heroin users and synthetic cannabinoid users were compared with healthy volunteers (n=32) using two-dimensional (2D) speckle-tracking (ST) echocardiography.ResultsNo differences were found in the baseline characteristics and 2D echocardiography values. The mean global longitudinal strain value was −20.5%±2.4% for SCB users, −22.3%±2.4% for opioid users, and −22.5%±2.2% for healthy volunteers (p=0.024). The mean apical 2-chamber (AP2C) L-strain values were −20.1%±3.1%, −22.4%±3.0%, and −22.3%±2.8% for SCB users, opioid users, and healthy volunteers, respectively (p=0.032). The mean apical 4-chamber (AP4C) L-strain values were −20.7%±2.5% for SCB users, −23.2%±3.2% for opioid users, and −23.8%±3.1% for healthy volunteers (p<0.001).ConclusionSCBs are potential causes of subclinical left ventricular dysfunction.

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Section: Endocannabinoids In Cellular Mechanisms Of Myocardial Adaptamentioning

confidence: 99%

“…Based on our data from cardiomyocytes in vitro and macrophage modulation in vivo we further investigated cellular interactions between cardiomyocytes and macrophages [50]. Initially we demonstrated the topical expression of CB2 receptor on WT cardiomyocytes and both WT macrophage subtypes M1 and M2 in cell culture, which increased under hypoxic conditions (2% O 2 ) and even more when proinflammatory cytokine interferon (IFN)-γ was added into the culture medium [50]. In order to exclude methodological problems of cell culture we quantified the number of vital WT cardiomyocytes in the culture after 12 and 24 hours cultivation under normoxia and hypoxia and found comparable cell numbers in both conditions, while the number was slightly lower after 24 hours indicating only minor loss due to apoptosis.…”

Section: Endocannabinoids In Cellular Mechanisms Of Myocardial Adaptamentioning

confidence: 99%

“…This raised the question whether the increased apoptosis alone is solely responsible for the loss of cardiomyocytes observed in our in vivo model, and we therefore investigated the function of macrophages in the next step. We stimulated the macrophages with IFN-γ in order to stimulate the differentiation into M1 subtype [50]. In order to measure the migration potential of this subtype we used either supernatant from the cardiomyocytes cell culture after 24 hours hypoxia or potent chemoattractants CCL2 and M-CSF in a Boyden chamber, which are both strongly induced after myocardial infarction in mice [51].…”

Section: Endocannabinoids In Cellular Mechanisms Of Myocardial Adaptamentioning

confidence: 99%

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The Role for the Endocannabinoid System in Cardioprotection and Myocardial Adaptation

Dewald¹,

Duerr²

2016

Cannabinoids in Health and Disease

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Results from different studies showing CB receptor-associated cardioprotective action are still fairly controversial and no single specific mechanism could be identified. Several groups investigated the involvement of the endocannabinoid system in cellular systems and function of cardiomyocytes, fibroblasts, macrophages and endothelial cells. While some studies are limited in their translational relevance, a few recent studies describe a myocardial ischemia and reperfusion scenario in a fashion comparable to the clinical situation. Recent studies provided evidence for involvement of the CB receptor endocannabinoid axis in prevention of cardiomyocyte apoptosis including modulation of antioxidative enzymes and contractile elements expression. CB receptor has further been shown to specifically modulate the inflammatory response and macrophage function after myocardial ischemia. These effects have an impact on the subsequent myocardial remodeling, where the CB receptor modulates function of myofibroblasts, collagen production and limitation of myocardial infarction size. Recent experimental and clinical data showed the association of the endocannabinoid system in myocardial hypertrophy. In conclusion, increasing amount of evidence supports a crucial role of the endocannabinoid system in cardioprotection and myocardial remodeling, while some of them even suggest model-independent systemic effects in adaptation of cardiomyocytes or components of the extracellular matrix.

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CB2 receptor-mediated effects of pro-inflammatory macrophages influence survival of cardiomyocytes

Cited by 21 publications

References 48 publications

Cannabinoid CB1/CB2 Receptors in the Heart: Expression, Regulation, and Function

Cannabinoid CB1/CB2 Receptors in the Heart: Expression, Regulation, and Function

Speckle Tracking Strain Assessment of Left Ventricle in Synthetic Cannabinoid and Heroin Users

The Role for the Endocannabinoid System in Cardioprotection and Myocardial Adaptation

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