Endocannabinoid system

Endocannabinoid system

Endocannabinoid system (ECS) is a system composed of cannabinoid receptors, cannabinoid ligands, enzymes and proteins that synthesize, transport and degrade them. ECs and 2-arachi-donoylglycerol (2-AG) and n-arachidonoylethanolamide (AEA) have been widely studied. A variety of factors, such as metabolic receptors (such as dopamine) or ionic receptors (such as ca2+), are beneficial to the synthesis of ECs. CB1 receptors and CB2 receptors are located on the cell surface. CB1 receptors are distributed in the whole brain, and are rich in basal ganglia, hippocampus and other regions, and participate in the regulation of synaptic plasticity. CB2 receptor in normal brain tissue is up-regulated in activated microglia after chronic pro-inflammatory stimulation. ECS acts on synapses when the body needs it.

CB1 mainly exists in the central and peripheral nervous system, and in various peripheral tissues, including the heart and blood vessels; CB2 is mainly distributed in immune system and hematopoietic cells, central nervous system and heart. Cannabinoids play a role in vasodilation, bradycardia, hypotension, inhibition of myocardial contraction, anti-inflammatory and protection of endothelial cells. Cannabinoids have a broad application prospect in the prevention and treatment of cardiovascular diseases.

The role of ECs in cardiovascular diseases

CB1 receptors are distributed in cerebellum, basal ganglia, hippocampus and cortex. It is found in other areas, such as the brainstem, where the regulatory center of respiratory and cardiovascular function is located. In the cardiovascular system, CB1 receptors are located in myocardium, vascular endothelial cells and smooth muscle cells. Studies have found that the heart can promote inflammation, oxidation and fibrosis under disease conditions when CB1 is activated. These effects include increasing the formation of reactive oxygen species, inflammatory cytokines, adhesion molecules, apoptotic signaling pathways and collagen accumulation. Compared with other anti-inflammatory drugs for the treatment of atherosclerosis, drug inhibition of CB1 receptor signal has the advantage of anti atherosclerotic effect by avoiding vascular inflammation and improving the prognosis after myocardial infarction

CB2 receptor is expressed in cardiomyocytes, coronary artery endothelial cells and smooth muscle cells. CB2 receptor is expressed in immune cells such as leukocytes and macrophages. These cells participate in the control of inflammation and cardiac tissue damage. The activation of CB2 receptor has anti fibrosis function in skin and heart. Pharmacological activation of CB2 receptor in bleomycin model experiment of systemic sclerosis (SSC) not only reduces dermal thickness and collagen accumulation around blood vessels, but also prevents mast cell degranulation and macrophage infiltration in skin

Activation of CB2 receptor triggers anti-inflammatory and anti fibrosis effects. In the experimental model of myocardial interstitial fibrosis, the activation of CB2 receptor decreased the increase of type I collagen and type III collagen CB2 deficient mice are more sensitive to fibrosis progression after myocardial infarction (MI).

Endogenous cannabinoid concentration and inhibitor are the main compounds that block degradation. The positive effects of inhibitors have been studied in many pathological states, such as nervous system, gastrointestinal and cardiovascular diseases, hypertension and cerebrovascular diseases, the enhancement of endogenous cannabinoid tension, and the reduction of the level of lipid mediators involved in insulin resistance, which trigger the protective mechanism of the heart. Inhibitors reduce blood pressure and are the regulators of myocardial lipid metabolism in spontaneous hypertension As the treatment of cardiovascular and metabolic diseases, it provides an important research direction and role.

Regulation of ECS on cardiovascular function

Cardiac effects co-exist in atrial myocytes, CB1 and CB2 receptors belonging to G-protein coupled receptors. Endogenous cannabinoids participate in the regulation of cardiovascular function through CB1 receptors. Studies have found that endogenous cannabinoid CB1 receptor agonists reduce atrial contractility in a concentration dependent manner. Presynaptic CB1 receptors with sympathetic nerves inhibit norepinephrine release. The effect of reducing heart rate, myocardial systolic and diastolic rate was blocked by CB1 receptor antagonist. Endocannabinoids are involved in the regulation of myocardial systolic and diastolic function and heart rate through a CB1 receptor independent pathway.

Cannabinoid in the treatment of cardiovascular diseases

Cardiac fibrosis is a major pathological disease associated with numerous cardiovascular diseases. It is characterized by abnormal accumulation of extracellular matrix proteins in the heart, accompanied by activation of cardiac fibroblasts. These two are components of most cardiac pathological conditions After ischemia injury or pressure overload, the heart undergoes a dynamic remodeling process coordinated by cardiomyocytes, endothelial cells, immune cells and cardiac fibroblasts. Myocardial repair ability is low, and ventricular fibrosis remodeling occurs in diseases related to acute myocardial cell death. Myocardial fibroblasts differentiate from myofibroblasts that produce pro-inflammatory cytokines, leading to proliferation of non myocytes and increased production of extracellular matrix (ECM) proteins, such as fibronectin and collagen deposition in myocardial tissue

To study how to prevent immune related myocardial injury and autoimmune myocarditis by enhancing the protective and anti-inflammatory effects of CBD in adenosine A2A receptor The reduction of initial myocardial injury by CBD is associated with acute events such as oxidative stress and activation of death signaling pathway In fact, CBD alleviates diabetes related myocardial fibrosis. A new role of CBD in cardiovascular disease in the mouse model, defective mice have stronger resistance to oxidative stress related to cardiovascular disease. CBD ablation protects mouse myocardium from ischemia-reperfusion and its lack of protection against atherosclerosis

The role of ECs in cardiovascular diseases

CB1 receptors are distributed in cerebellum, basal ganglia, hippocampus and cortex. It is found in other areas, such as the brainstem, where the regulatory center of respiratory and cardiovascular function is located. In the cardiovascular system, CB1 receptors are located in myocardium, vascular endothelial cells and smooth muscle cells. Studies have found that the heart can promote inflammation, oxidation and fibrosis under disease conditions when CB1 is activated. These effects include increasing the formation of reactive oxygen species, inflammatory cytokines, adhesion molecules, apoptotic signaling pathways and collagen accumulation. Compared with other anti-inflammatory drugs for the treatment of atherosclerosis, drug inhibition of CB1 receptor signal has the advantage of anti atherosclerotic effect by avoiding vascular inflammation and improving the prognosis after myocardial infarction

CB2 receptor is involved in the control of inflammation and cardiac tissue damage in cardiac myocytes, coronary artery endothelial cells, smooth muscle cells, leukocytes and macrophages. CB2 receptor has the role of cardiac protection Activation of CB2 receptor has anti fibrosis function in skin and heart. Pharmacological activation of CB2 receptor in bleomycin model experiment of systemic sclerosis (SSC) not only reduces dermal thickness and collagen accumulation around blood vessels, but also prevents mast cell degranulation and macrophage infiltration in skin

Activation of CB2 receptor triggers anti-inflammatory and anti fibrosis effects. In the experimental model of myocardial interstitial fibrosis, the activation of CB2 receptor decreased the increase of type I collagen and type III collagen CB2 deficient mice are more sensitive to fibrosis progression after myocardial infarction (MI).

Outlook and future

Cannabinoid ECS plays an important role in the regulation of cardiovascular processes, and the regulation of ECB tension is considered to be a promising method for the treatment of heart diseases. This method is beneficial to various diseases, such as metabolic equivalent and cardiac fibrosis. Considering the significant complexity of ECs, the effect of ECS modulation needs to be further studied. New research is providing research direction for improving the process of identifying new drugs and therapeutic targets. The continuous in-depth study on the cardiovascular mechanism of ECS will provide a new way for the prevention and treatment of a variety of cardiovascular diseases