The important place of cell death and/or impaired endothelial activity in vascular dysfunction development cannot be overemphasized. It is associated with several conditions, like atherosclerosis, coronary artery disease, hypertension, diabetic complications, congestive heart failure and cancer.
Lots of evidence is coming to the fore about the beneficial effect of the inhibition of cannabinoid receptor 1 (CB1) in the management of conditions like inflammation and atherosclerosis in both humans and experimental models. This paper will investigate the impact of the activation of the CB1 receptor with the synthetic agonist or endocannabinoid anandamide on interrelated signal transduction pathways and cell death in the primary coronary artery endothelial cells in humans.
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Activation of signal transduction pathways, reactive oxygen species (ROS) generation, receptor expression and cell death were determined via molecular biology and flow cytometry tools. The activation of endothelial cells by the CB1 receptor is equally involved in the process. It may activate the endothelial cells and amplify the ROS-MAPK activation-cell death pathway in pathological conditions. As a result, it can contribute to endothelial dysfunction development and multiple cardiovascular disease pathophysiology.
The endothelial cells generate vasoconstriction and vasodilating substances. The production is consequent of several physical and chemical stimuli, like substances released by platelets, autonomic nerves, sensory nerve, as well as drugs, circulating hormones, cytokines, shear stress, and change in pressure. The secretion equally includes substances responsible for regulating inflammation, angiogenesis, homeostasis, permeability and regulates vascular tone.
The intact vascular endothelium maintains the balance between the stimulation and prevention of platelets aggregation, inhibition of smooth muscle cell proliferation, promotion, fibrinolysis, thrombogenesis and platelet aggregation. The process also concerns substances that can regulate conditions like inflammation, angiogenesis, hemostasis, permeability and vascular tone.
ROS Generation Detection
Activated endothelial cells can equally play an important role in the production of different pro-inflammatory mediators, like adhesion molecules, chemokines, and cytokines. It equally affects reactive oxygen/nitrogen species and equally involved in the orchestration of immune cell activation and migration to the site where tissue injury occurs.
Also cell death and/or impaired endothelial homeostasis are contributory to the development of dysfunctions and vascular inflammatory responses; the dysfunctions are associated with multiple diseases that range from cardiovascular aging, atherosclerosis and coronary artery disease to diabetic complications, hypertension, and congestive heart failure.
The CB1 pharmacological inhibition or activation limits the interrelated disease progression and vascular inflammation, as well as reduce proliferation of smooth muscles in pre-clinical models of atherosclerosis. Some of the benefits of the CB1 antagonist on a condition like atherosclerosis have been shown in humans having diabetes and/or obesity, as well as metabolic syndrome. The expression of CB1 receptors occurs in the cardiomyocytes and endothelial cells.
Cardiovascular CB1 Receptors activation via excess endocannabinoids has been implicated in pathophysiological alteration development, which is associated with heart failure, cirrhotic cardiovascular dysfunction, cardiogenic shock, hemorrhagic shock and septic shock. Studies are revealing that the activation of the CB1 receptor in different pathological conditions with endocannabinoids may cause the promotion of signaling pathway activation, which further promotes cell death. This is the basic reason for investigating the impacts of the CB1 receptor activation on conditions like human coronary artery endothelial cells (HCAECs), ROS generation and cell death.
The above information shows the relationship between ROS system dependent and independent protein kinase derived from mitogen-activation and how the condition can accelerate cell death and other related conditions. It also investigates the effects of the activation of the CB1 receptor on several health conditions. Conclusively, the pathological disruption of regulated endothelial homeostasis culminates in endothelial dysfunction development.