What are endothelial cells and why are they so important?

Endothelial cells form a single cell layer (tunica intima) that lines the entire vascular system, from the heart to the smallest capillary.¹ 

It is surrounded by two additional layers; a middle layer (tunica media) consisting of vascular smooth muscle cells, and the outermost layer (tunica externa) which contains fat cells, fibroblast cells, collagen and nerve endings.²

Figure 1 | Structure of arterial walls.²

However, the endothelium is not just a simple barrier; it plays an important and overarching role as a ‘gatekeeper’ of the entire cardiovascular system by regulating:^1-4

• Transport and vascular permeability (passage of nutrients and drugs)
• Blood vessel diameter/vascular tone (vasoconstriction and relaxation)
• Fibrinolysis (antithrombotic mechanisms)
• Platelet aggregation (anticoagulant mechanisms)
• Adhesion of monocytes/leukocyte (immune mechanisms)
• Angiogenesis (blood vessel formation)
• Inflammatory mechanisms

Endothelial cells are metabolically active and have a remarkable ability to adapt to local changes by releasing specific vasoactive mediators, in particular nitric oxide (NO), which influences many of the above-mentioned processes.⁴ It is this role in NO production that makes the endothelium an important therapeutic target in cardiovascular disease.

In contrast, endothelial dysfunction - which is characterised by abnormal vasodilation and vasoconstriction, increased reactive oxygen species (ROS), inflammation, and diminished bioavailability of NO - contributes to the initiation and progression of a plethora of vascular disorders, including cardiovascular diseases (CVDs) (see figure 2).^3-7

Cardiovascular risk factors and endothelial dysfunction

Modifiable risk factors for endothelial dysfunction and the resulting vascular changes (atherothrombosis) are largely based on preventable habits, such as an unhealthy diet, physical inactivity, tobacco use and high alcohol consumption. Likewise, other risk factors such as chronic inflammation, infection, environmental stress and mental-emotional stress are partly preventable or treatable (see figure 2).^3,5,6 Considering that only advancing age and genetic predisposition are non-modifiable, the majority of risk factors can be mitigated in clinical practice through targeted treatment interventions. Irrespective of the cause, all risk factors collectively impair NO-dependent signalling, which leads to the disruption of the homeostatic balance between NO and O2 (oxygen). It is this loss of balance which plays a central role in the causation of oxidative stress and low-grade inflammation,⁶ and therefore the initiation or acceleration of atherosclerosis. ^7,8

Figure 2 | Cardiovascular risk factors and manifestations of cardiovascular disease.⁶

How herbal medicines support endothelial health

Given the importance of a healthy endothelium, it is prudent to prevent and treat the root causes of vascular dysfunction. While clinicians will need to address the underlying risk factors outlined above, herbal medicines such as Gingko biloba (Ginkgo), Vitis vinifera (Grape seed) and Centella asiatica (Gotu kola) are especially suitable for supporting the endothelium as they provide a multitude of actions that work synergistically on various targets. Table 1 below summarises their endothelium-focused and cardiovascular-protective actions.

Table 1 | Endothelium-focused & cardiovascular-protective actions of Ginkgo, Grape seed & Gotu kola

*Inhibition of PAF might increase cardiac contractility and coronary blood flow.²⁴

Conclusion

Endothelial dysfunction is an important underlying and often preventable cause of cardiovascular disease. However, Ginkgo, Grape Seed and Gotu Kola possess many therapeutic actions that are endothelium-focused and cardioprotective, thereby offering valuable and safe treatment options for clinicians to use in at risk patients.

References

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