Category Archives: Cardiovascular Disease

Signaling Pathways Involved in the Cardioprotective Effects of Cannabinoids

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jphs

“The aim of the present article is to review the cardioprotective properties of cannabinoids, with an emphasis on the signaling pathways involved.

Cannabinoids have been reported to protect against ischemia in rat isolated hearts, as well as in rats and mice in vivo.

Finally, although nitric oxide (NO) was shown to exert both pro and anti-apoptotic effects on cardiomyocytes, with an apparently controversial effect on myocardial survival, our data suggest that NO may contribute to the cardioprotective effect of some cannabinoids.”

“Signaling pathways involved in the cardioprotective effects of cannabinoids.”  http://www.ncbi.nlm.nih.gov/pubmed/17031075

https://www.jstage.jst.go.jp/article/jphs/102/2/102_2_155/_article

6B.09: EFFECT OF CANNABINOID RECEPTOR ACTIVATION ON ABERRANT MITOCHONDRIAL BIOENERGETICS IN HYPERTROPHIED CARDIAC MYOCYTES.

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“We recently reported that activation of endocannabinoid receptors attenuates cardiac myocyte hypertrophy. Mitochondrial dysfunction has emerged as a critical determinant of aberrant myocyte energy production in cardiac hypertrophy. Thus, we determined endocannabinoid influence on mitochondrial function in the hypertrophied cardiac myocyte…

The cardioprotective actions of liganded cannabinoid receptors extend to the mitochondrial level. Therefore, a cannabinoid-based treatment for cardiac disease remains a potential therapeutic strategy that warrants further study.”

http://www.ncbi.nlm.nih.gov/pubmed/26102932

CB1 cannabinoid receptor antagonist attenuates left ventricular hypertrophy and Akt-mediated cardiac fibrosis in experimental uremia.

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“Cannabinoid receptor type 1 (CB1R) plays an important role in the development of myocardial hypertrophy and fibrosis-2 pathological features of uremic cardiomyopathy. However, it remains unknown whether CB1R is involved in the pathogenesis of uremic cardiomyopathy.

Here, we aimed to elucidate the role of CB1R in the development of uremic cardiomyopathy via modulation of Akt signalling…

CB1R inhibition exerts anti-fibrotic effects via modulation of Akt signaling in H9c2 myofibroblasts.

Therefore, the development of drugs targeting CB1R may have therapeutic potential in the treatment of uremic cardiomyopathy.”

Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1 activation.

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“The protective effects of cannabidiol (CBD) have been widely shown in preclinical models and have translated into medicines for the treatment of multiple sclerosis and epilepsy. However, the direct vascular effects of CBD in humans are unknown.

CONCLUSION:

This study shows, for the first time, that CBD causes vasorelaxation of human mesenteric arteries via activation of CB1 and TRP channels, and is endothelium- and nitric oxide-dependent.”

http://www.ncbi.nlm.nih.gov/pubmed/26092099

Bi-directional CB1 receptor-mediated cardiovascular effects of cannabinoids in anaesthetized rats: role of the paraventricular nucleus.

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“The activation of cannabinoid CB1 receptors decreases and increases blood pressure (BP) in anaesthetized and conscious rats, respectively. The aim of our study was to check the possible involvement of CB1 receptors in the paraventricular nucleus of the hypothalamus (PVN) in the cardiovascular effects of cannabinoids in rats.

In conclusion, the cannabinoid CP55940 administered to the PVN of urethane-anaesthetized rats can induce depressor and pressor effects. The direction of the response probably depends on the sympathetic tone. The centrally induced hypertensive response of CP55940 can, in addition, be masked by peripheral CB1 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/26084216

Pharmacologic effects of cannabidiol on acute reperfused myocardial infarction in rabbits: evaluated with 3.0T cardiac magnetic resonance imaging and histopathology.

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“Cannabidiol (CBD) has anti-inflammatory effects.

We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform…

Compared to controls, CBD treatment improved systolic wall thickening, significantly increased blood flow in the AAR, significantly decreased microvascular obstruction, increased the PDR by 1.7-fold, lowered the AMI-core/AAR ratio, and increased the MSI.

These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis.

Thus, CBD therapy reduced AMI size and facilitated restoration of LV function.

We demonstrated that this experimental platform has potential theragnostic utility.”

http://www.ncbi.nlm.nih.gov/pubmed/26065843

Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.

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“The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer.

Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25970609

The effect of endocannabinoid system in ischemia-reperfusion injury: a friend or a foe?

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“In recent years, the endocannabinoid system has emerged as a new therapeutic target in variety of disorders associated with inflammation and tissue injury, including those of the neuronal, liver, renal and cardiovascular system.

The aim of the present review is to elucidate the effect of endocannabinoid system on ischemia reperfusion injury (IRI) in different organs and systems.

Expert opinion: CB2 receptors may play an important compensatory role in controlling tissue inflammation and injury in cells of the neuronal, cardiovascular, liver and renal systems, as well as in infiltrating monocytes/macrophages and leukocytes during various pathological conditions of the systems (atherosclerosis, restenosis, stroke, myocardial infarction, heart, liver and renal failure).

These receptors limit inflammation and associated tissue injury.

On the basis of preclinical results, pharmacological modulation of CB2 receptors may hold a unique therapeutic potential in stroke, myocardial infarction, atherosclerosis, IRI and liver disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25936364

Cannabis and cardiotoxicity.

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“Cannabis is the most commonly consumed illicit drug… Despite the drug’s extreme popularity, reports of cannabis-related stroke and myocardial infarction are so rare as to still be reportable… The observation that cardiotoxicity has never been reported in cancer patients taking dronabinol, the synthetic form of THC, tends to suggest that animal studies may have overstated the cardiovascular risk,” http://www.ncbi.nlm.nih.gov/pubmed/25868498

http://www.thctotalhealthcare.com/category/cardiovascular-disease/

The cannabinoid receptor 2 is involved in acute rejection of cardiac allografts.

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“Acute rejection of cardiac allografts is a major risk factor limiting survival of heart transplant recipients. Rejection is triggered by dendritic cell (DC) mediated activation of host T cells, amongst others CD4+ T helper (TH)1- and TH17 cells.

The cannabinoid receptor 2 (CB2) is an important modulator of cellular immune responses…

These results demonstrate that CB2 modulates in vitro cytokine responses via DCs and directly via its influence on TH1/TH17 differentiation.

These findings and the fact that allograft rejection is enhanced in Cnr2-/- mice suggest that CB2 may be a promising therapeutic target in organ transplantation.”

http://www.ncbi.nlm.nih.gov/pubmed/25744392