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Different expression and function of the endocannabinoid system in human epicardial adipose tissue in relation to
Giuseppe Cappellano1, Francesca Uberti, Philippe Primo Caimmi
1Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy. giuseppe.cappellano@med.unipmn.it
Insights
The endocannabinoid system differs in heart disease patients. Ischemic patients show higher CB1 receptor and PKA activation, linked to poorer outcomes, while non-ischemic patients exhibit increased CB2 receptor expression, suggesting therapeutic potential.
Area of Science:
- Cardiology
- Molecular Biology
- Endocrinology
Background:
- The endocannabinoid system is implicated in cardiovascular disease pathogenesis.
- Adipose tissue, expressing this system, may influence cardiac disorders via inflammation.
Purpose of the Study:
- To investigate the role of the endocannabinoid system in epicardial adipose tissue concerning heart disease.
Main Methods:
- Western blot analysis of CB1, CB2 receptors, fatty acid amidohydrolase, and signaling pathways (PKA, PLC, PKC, eNOS, iNOS, ERK1/2).
- Analysis performed on epicardial adipose tissue from coronary artery bypass (ischemic) and valve surgery (non-ischemic) patients.
Main Results:
- Ischemic patients showed a higher CB1-to-CB2 ratio and increased PKA activation.
- Non-ischemic patients had upregulated CB2, fatty acid amidohydrolase, PLC, PKC, and ERK1/2.
- Ischemic preadipocytes exhibited higher nitric oxide production and iNOS-to-eNOS ratios.
Conclusions:
- Distinct endocannabinoid system modulation occurs in ischemic versus non-ischemic heart disease.
- High CB1 and PKA expression correlate with poor survival pathways and iNOS activation in ischemic heart disease.
- Targeting the endocannabinoid system in ischemics may offer therapeutic strategies for cardiac dysfunction.
Background:
The endocannabinoid system reportedly plays a role in the pathogenesis of cardiovascular diseases. This system is expressed also in adipose tissue, which could thus be involved in cardiac disorders through modulation of metabolically triggered inflammation. The current study aims to determine the relevance of the endocannabinoid system in epicardial adipose tissue in heart disease.
Methods:
Expression of the endocannabinoid receptors CB1 and CB2, and of the endocannabinoid-degrading enzyme, fatty acid amidohydrolase, and activation of protein kinase A (PKA), phospholipase C (PLC), protein kinase C (PKC), endothelial nitric oxide synthase (eNOS) and inducible (i)NOS, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (a member of the reperfusion-injury salvage kinase pathway), were analyzed by Western blot in patients after coronary artery bypass surgery (ischemics; N = 18) or valve surgery (nonischemics; N = 15) and in preadipocytes isolated from epicardial adipose tissue.
Results:
In ischemics, the CB1-to-CB2 expression ratio shifted toward CB1 and was accompanied by higher PKA activation. In contrast, in nonischemics, CB2, fatty acid amidohydrolase, PLC and PKC, and ERK1/2 were upregulated. Moreover, NO production and iNOS-to-eNOS ratios were higher in preadipocytes from ischemics.
Conclusions:
These results show a different modulation and functioning of the endocannabinoid system in ischemics compared with nonischemics. Hence, while CB2, PLC and PKC, ERK1/2, and eNOS are more strongly expressed in patients without ischemic heart disease, high CB1 and PKA expression is associated with low survival intracellular pathway activation and high iNOS activation in ischemic heart disease patients. The changes in the endocannabinoid system in ischemics may contribute to cardiac dysfunction and therefore represents a potential therapeutic target.