Endothelial cells line your blood vessels, tightly joined together to keep your blood where it is supposed to be flowing. But the endothelium is more than just a lining or a barrier — it is also the largest organ in the body.
The endothelium regulates the constriction and relaxation of blood vessels, regulates the way platelets and white blood cells interact with the wall of the blood vessels, and regulates the proliferation of new blood vessels. The endothelial cells act together to coordinate and release relaxing or constricting factors to regulate blood pressure. For example, nitric oxide is produced and released in the endothelium as a vasodilator (relaxing factor) and angiotensin II is released as a vasoconstrictor.[ref]
A study published in January 2022 explains how the spike protein causes endothelial dysfunction.[ref – full pdf]
While the role of the ACE2 receptor was shown on every news report with cute graphics, the paper explains that spike protein can bind to cells in other ways as well. Importantly for endothelial function, integrins can also bind to the spike protein. Integrins are cell adhesion molecules that are expressed on the surface of cells and interact with the extracellular matrix or with neighboring cells.[ref]
A specific integrin, integrin ⍺5β1, may be at the heart of many vascular-driven problems seen in covid, long covid, and long spike…
The RGD sequence located in the spike protein receptor binding domain is the same binding motif of other substances that bind to integrin ⍺5β1 — including fibronectin. Fibronectin is a protein that binds to integrins and the extracellular matrix, playing a vital role in tissue repair and wound healing. Binding with integrin ⍺5β1 triggers NF-kB activation and inflammation. NF-kB is a transcription factor that is usually inactive, but when activated it triggers the formation of a bunch of inflammatory cytokines.
The researchers found that spike protein binding to integrin ⍺5β1 activated NF-kB in the endothelial cells and allowed leukocyte attachment. This started the cascade of inflammatory cytokines and coagulation factor release that is seen in Covid. The researchers could stop the whole cascade of spike-induced inflammation with a combination of integrin ⍺5 antibodies (blocking integrin ⍺5β1 attachment) and inhibiting NF-kB[ref – full pdf]
This isn’t the only study or research group making the connection between the full-length spike protein and binding with integrins to cause endothelial dysfunction.
Another group of researchers from Berkely showed that the full-length spike protein (without the rest of the virus) can cause endothelial barrier dysfunction independently of ACE2. These researchers also demonstrated that integrins, glycosaminoglycans, and TGF-B signaling interact with the spike protein to cause endothelial dysfunction. Moreover, inhibiting integrins could stop vascular leakage.[ref]