Sex differences in distribution of cannabinoid receptors (CB1 and CB2), S100A6 and CacyBP/SIP in human ageing hearts

Piotrowska, Żaneta; Niezgoda, Michał; Łebkowski, W; Filipek, Anna; Domian, Natalia; Kasacka, Irena

doi:10.1186/s13293-018-0209-3

Cited by 15 publications

(22 citation statements)

References 41 publications

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“…Increased female expression of ABHD6 has been previously reported in immune cells, with only female cells showing estrogen- or progesterone-dependent induction of ABHD6 gene levels. Our observations of minor sex-dependent effects on the expression of the 27-gene endocannabinoid signature contrast with sex differences in the expression of CB 1 and CB 2 protein expression in heart tissue, where CB 1 receptors are more highly expressed in females and CB 2 receptors more highly expressed in males(94). Our observations of limited impact of sex on the 27-gene endocannabinoid signature expression in healthy subjects were conserved in asthmatics and individuals with COPD.…”

Section: Discussioncontrasting

confidence: 77%

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Expression of the endocannabinoid system in the human airway epithelial cells – Impact of sex and chronic respiratory disease status

Fantauzzi

Aguiar

Tremblay

et al. 2020

Preprint

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Recreational and medicinal cannabis consumption in the past 12 months has been reported in 1/5th of Canadians, with greater use in males relative to females. Cannabis smoking is the dominant route of delivery in consumers, with the airway epithelium functioning as the site of first contact for inhaled phytocannabinoids. The endocannabinoid system is responsible for mediating the physiological effects of inhaled phytocannabinoids. Acute cannabis smoke inhalation can result in bronchodilation, which may have applications in chronic respiratory disease management. In contrast, chronic cannabis smoke inhalation is associated with reduced lung function and bronchitis, which challenges potential applications in the lung. The contribution of the endocannabinoid system in the airway epithelium to either beneficial or harmful physiological responses remains to be clearly defined in males and females and those with underlying chronic respiratory disease.To begin to address this knowledge gap, a curated dataset of 1090 unique human bronchial brushing gene expression profiles was created from Gene Expression Omnibus deposited microarray datasets. The dataset included 616 healthy subjects, 136 subjects with asthma, and 338 subjects with COPD. A 27-gene endocannabinoid signature was analyzed across all samples with sex and disease specific-analyses performed. Immunohistochemistry and immunoblots were performed to confirm in situ and in vitro protein expression of select genes in human airway epithelial cells.We confirm three receptors for cannabinoids, CB1, CB2, and TRPV1, are expressed at the protein level in human airway epithelial cells in situ and in vitro, justifying examining the downstream endocannabinoid pathway more extensively at the gene expression level. Sex status was associated with differential expression of 6/27 genes. In contrast, disease status was associated with differential expression of 18/27 genes in asthmatics and 22/27 genes in COPD subjects. We confirm at the protein level that TRPV1, the most differentially expressed candidate in our analyses, was up-regulated in airway epithelial cells from asthmatics relative to healthy subjects.Our data demonstrate that endocannabinoid system is expressed in human airway epithelial cells with expression impacted by disease status and minimally by sex. The data suggest that cannabis consumers may have differential physiological responses in the respiratory mucosa, which could impact both acute and chronic effects of cannabis smoke inhalation.

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Section: Discussioncontrasting

confidence: 77%

“…Sex differences in CB 1 and CB 2 expression levels have been reported(94), which could impact downstream responses to cannabinoid exposures. Furthermore, sex and gender differences in cannabis consumption practices have been reported(2-4).…”

Section: Resultsmentioning

confidence: 99%

Expression of the endocannabinoid system in the human airway epithelial cells – Impact of sex and chronic respiratory disease status

Fantauzzi

Aguiar

Tremblay

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Sex differences in CB 1 and CB 2 expression levels have been reported [ 98 ], which could impact downstream responses to cannabinoid exposures. Furthermore, sex and gender differences in cannabis consumption practices have been reported [ 2 – 4 ].…”

Section: Resultsmentioning

confidence: 99%

Expression of endocannabinoid system components in human airway epithelial cells: impact of sex and chronic respiratory disease status

et al. 2020

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Cannabis smoking is the dominant route of delivery, with the airway epithelium functioning as the site of first contact. The endocannabinoid system is responsible for mediating the physiological effects of inhaled phytocannabinoids. The expression of the endocannabinoid system in the airway epithelium and contribution to normal physiological responses remains to be defined.To begin to address this knowledge gap, a curated dataset of 1090 unique human bronchial brushing gene expression profiles was created. The dataset included 616 healthy subjects, 136 subjects with asthma, and 338 subjects with COPD. A 32-gene endocannabinoid signature was analysed across all samples with sex and disease specific-analyses performed. Immunohistochemistry and immunoblots were performed to probe in situ and in vitro protein expression.CB1, CB2, and TRPV1 protein signal is detectable in human airway epithelial cells in situ and in vitro, justifying examining the downstream endocannabinoid pathway. Sex status was associated with differential expression of 7/32 genes. In contrast, disease status was associated with differential expression of 21/32 genes in asthmatics and 26/32 genes in COPD subjects. We confirm at the protein level that TRPV1, the most differentially expressed candidate in our analyses, was up-regulated in airway epithelial cells from asthmatics relative to healthy subjects.Our data demonstrate that endocannabinoid system is expressed in human airway epithelial cells with expression impacted by disease status and minimally by sex. The data suggest that cannabis consumers may have differential physiological responses in the respiratory mucosa.

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“…The activation of the CB1R in isolated rat atria results in feeble cardiomyocyte contractility [59]. Numerous in vivo studies have demonstrated that activation of CB1R promotes cardiomyocyte injury, oxidative stress, inflammation, and fibrosis, and augments collagen deposition and cardiomyocyte overgrowth [60,61,62]. Thus, chronic inhibition of CB1R with rimonabant improves cardiac functions in the early and late stages after myocardial infarction, decreases arterial stiffness, and reduces cardiac remodeling [63,64].…”

Section: Distribution and Biological Roles Of Cb1r In The Human Bodymentioning

confidence: 99%

Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications

Nagappan

Shin

Jung

2019

IJMS

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Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses. Additionally, blocking peripheral CB1R improves insulin sensitivity and glucose metabolism and also reduces hepatic steatosis and body weight in obese mice. Thus, targeting EC receptors, especially CB1R, may provide a potential therapeutic strategy against obesity and insulin resistance. There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance. Recently, the use of CB1R antagonists was suspended due to adverse central effects, and this caused a major setback in the development of CB1R antagonists. Recent studies, however, have focused on development of antagonists lacking adverse effects. In this review, we detail the important role of CB1R in hepatic insulin resistance and the possible underlying mechanisms, and the therapeutic potential of CB1R targeting is also discussed.

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Sex differences in distribution of cannabinoid receptors (CB1 and CB2), S100A6 and CacyBP/SIP in human ageing hearts

Cited by 15 publications

References 41 publications

Expression of the endocannabinoid system in the human airway epithelial cells – Impact of sex and chronic respiratory disease status

Expression of the endocannabinoid system in the human airway epithelial cells – Impact of sex and chronic respiratory disease status

Expression of endocannabinoid system components in human airway epithelial cells: impact of sex and chronic respiratory disease status

Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications

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