Do Endothelial Cells Lining Blood Vessels Express ACE2?
It’s a simple question, but a vital one, considering that cell entry and infection by the SARS-CoV-2 virus is primarily thought to occur via binding of the spike protein to ACE-2 receptors on the surface of cells throughout the body, particularly in the lungs. It’s vital because we need to know exactly how the spike protein is interacting with endothelial cells resulting in inflammation and the formation of the abnormal fibrous clots which embalmers are pulling out of corspes. I pointed out a very early 2020 study a few days ago which suggested that ACE-2 was not present in the endothelium:
Way back in 2004, with the advent of SARS, ACE2 was identified as the critical mode of entry of the virus and apparently it was found on cells all over the body, including endothelial cells. This study for example:
Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS-CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
They found ACE-2 receptors in lung epithelial cells but they also found them on endothelial cells. This study also from December 2020:
Existing studies suggested significant expression of ACE2 and TMPRSS2 in human vascular endothelium. Vascular endothelial dysfunction can potentially activate coagulation cascade eventually resulting in thrombosis. ACE2 has proven role in the maintenance of endothelial integrity inside the vessels. Existing in situ evidence for SARS-CoV-1 (the causative agent for SARS pandemic of 2002, which shared ACE2 as cell entry receptor) suggested that virus binding can downregulate ACE2, thus can induce endothelial dysfunction. Recently, in situ evidence has been presented that SARS-CoV-2 can infect cells in engineered human vascular endothelium, which can be effectively blocked by using clinical-grade recombinant human ACE2. Based on the circumstantial evidence present in the literature, we propose a SARS-CoV-2 cell entry receptor ACE2 based mechanism for vascular thrombosis in COVID-19 patients.
Also, from 2020, another study:
SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells. There is evidence that also endothelial cells are infected by SARS-COV-2, with subsequent occurrence of systemic vasculitis, thromboembolism and disseminated intravascular coagulation.
There’s plenty more where they came from. Even the brilliant and brave Dr. Peter McCullough (January 2021) identifies ACE-2 binding as the mechanism via which the virus infects endothelial cells:
You can’t argue with that. Or maybe you can. This is, after all, science, and science and scientific understanding are in a constant state of flux, where debate and disagreement are healthy. At least, that’s the way it used to be, until the social media censors and the girly Goebbels ‘fact checkers’, in thrall to governments and corporate sponsors came along, alleging that ‘misinformation, disinformation and malinformation’ must be snuffed out for public safety reasons.
This study was published in April 2022:
Evidence of widespread thrombosis with micro‐thrombosis seen in the vasculature of lungs, kidneys, and brain, and other organs together with the presence of biomarkers of vascular dysfunction in blood samples from severe COVID‐19 patients indicate a primary role for the endothelium in the disease process. It is recognized that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) primarily infects cells by using a viral surface glycoprotein (spike protein) which binds to angiotensin‐converting enzyme related carboxypeptidase (ACE2) on the target cell to gain entry. ACE2 is reported to be expressed on many cell types including lung epithelial and vascular endothelium as reported in the previous SARS‐CoV‐1 epidemic. 1 However, current research efforts are unable to demonstrate any or very low levels of ACE2 expression in human endothelial cells, 2 which poses a question as to how SARS‐CoV‐2 can infect and cause endotheliitis as widely reported.
Another study from March 2022 is titled:
SARS-CoV-2 Infects Human ACE2-Negative Endothelial Cells through an αvβ3 Integrin-Mediated Endocytosis Even in the Presence of Vaccine-Elicited Neutralizing Antibodies
Endothelial cells tested negative for ACE-2. Not only that; the authors also state:
Surprisingly, anti-Spike antibodies evoked by vaccination were not able to affect integrins/Spike interaction and therefore, SARS-CoV-2 infection.
Sorry? Could you repeat that please? Certainly:
Surprisingly, anti-Spike antibodies evoked by vaccination were not able to affect integrins/Spike interaction and therefore, SARS-CoV-2 infection.
Even in January 2021, some scientists were reporting that ACE-2 was very rare or absent on endothelial cells:
To support the hypothesis of direct viral damage of ECs via virus-induced infection, the cells should express the main receptor for SARS-CoV-2, ACE2 (angiotensin-converting enzyme 2), a metalloprotease component of the renin–angiotensin hormone system and a critical regulator of cardiovascular homeostasis.1 Indeed, several recent review articles propose that SARS-CoV-2 binding to ACE2 on ECs is the mechanism through which the virus may cause direct endothelial damage and endothelialitis.1 However, expression of ACE2 in ECs has not been convincingly demonstrated to support this assumption, nor has there been sufficient evidence to support a direct infection of ECs by SARS-CoV-2.
Publicly available single-cell RNA sequencing of human organ donor hearts2 showed that, while ACE2 sequence reads are abundant in pericytes, they are rare in ECs (Figure D). Of 100,579 ECs, only 468 (0.47%) were ACE2+, and in the majority (424), only a single ACE2 transcript was detected. This could reflect true low and rare endothelial ACE2 expression but also contamination from adherent pericyte fragments, a common confounder in vascular single-cell RNA sequencing data.3 If such fragments contributed to the ACE2 transcripts observed in certain ECs, we would expect to detect other pericyte transcripts in the same cells. Among the top-50 gene transcripts enriched in ACE2+ versus ACE2− ECs, we noticed several known pericyte markers, including PDGFRB, ABCC9, KCNJ8, and RGS5 (Figure E). Comparison of transcript abundance across the 3 major vascular and mesothelial cells showed that the top-50 gene transcripts were expressed at the highest levels in pericytes (Figure E). This suggests that the rare occurrence of ACE2 transcripts in human heart ECs is likely caused by pericyte contamination. Similar conclusions have been reached previously in mouse tissues.3
In other words, although ACE-2 is abundant in pericytes it is absent in human heart endothelial cells (it is interesting to note that pericytes are cells which wrap around the endothelial cells in small human blood vessels). The findings above are backed up by another study, published May 2022, carried out on mice:
Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells.
In summary then, the SC-2 spike protein, whether introduced through infection or by ‘vaccination’, is not binding to endothelial cells via ACE-2, causing inflammation and blood clotting, so something else must be responsible. The current emerging consensus is that this ‘something else’ is CD147, or basigin and the ‘something else’ is sparking off a catastrophic chain of events resulting in the ‘foot long’ rubbery white clots seen in ‘Died Suddenly’.