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The Spike Protein, Macrophages and Post-COVID (Spike Protein Exposure) Hypertension
In addition to endothelial cells, monocytes are also activated by the Spike Protein, which may explain the development of hypertension post-COVID/Spike Protein exposure.
WALTER M CHESNUT
JUN 23

https://open.substack.com/pub/wmcresearch/p/the-spike-protein-macrophages-and

峰值蛋白，巨噬细胞和杂化后（峰值蛋白暴露）高血压
除内皮细胞外，单核细胞还被尖峰蛋白激活，这可以解释高血压后/尖峰蛋白暴露后的高血压发育。
Walter M Chesnut
6月23日

Angiotensin II (Ang II) activates the microglia through the angiotensin type 1 receptor (AT1R) and promotes their polarization towards an M1 phenotype. Minocycline is a known inhibitor of Ang II mediated M1 polarization of microglia. M1 polarization of the microglia leads to activation of the sympathetic outflow from the central nervous system (CNS). Increased sympathetic outflow leads to 1) Increased expression of chemoattractant molecules (e.g. monocyte chemoattractant protein-1, MCP-1) in end-organs, such as the kidney. Simultaneously, increased sympathetic outflow mobilizes macrophages from immune cell reservoirs (e.g. spleen), while priming them for polarization towards an M1 phenotype. In response to increased expression of the chemoattractants in the kidney, macrophages infiltrate the renal medulla and are activated to polarize into the M1 phenotype. Renal and vascular inflammation leads to the development of hypertension. As hypertension develops, engagement of the AT1R directly on the surface of the macrophage results in M1 polarized macrohages “switching” into M2 macrophages, responsible for renal/vascular fibrosis and remodeling.
First, let’s read an Abstract... from 2009!
A purified recombinant spike (S) protein was studied for its effect on stimulating human peripheral blood monocyte macrophages (PBMC). We examined inflammatory gene mRNA abundances found in S protein-treated PBMC using gene arrays. We identified differential mRNA abundances of genes with functional properties associated with antiviral (CXCL10) and inflammatory (IL-6 and IL-8) responses. We confirmed cytokine mRNA increases by real-time quantitative(q) RT-PCR or ELISA. We further analyzed the sensitivity and specificity of the prominent IL-8 response. By real-time qRT-PCR, S protein was shown to stimulate IL-8 mRNA accumulation in a dose dependent manner while treatment with E protein did not. Also, titration of S protein-specific production and secretion of IL-8 by ELISA showed that the dose of 5.6 nM of S produced a significant increase in IL-8 (p = 0.003) compared to mock-treated controls. The increase in IL-8 stimulated by a concentration of 5.6 nM of S was comparable to concentrations seen for S protein binding to ACE2 or to neutralizing monoclonal antibody suggesting a physiological relevance. An NF-κB inhibitor, TPCK (N-Tosyl-L-Phenylalanine Chloromethyl Ketone) could suppress IL-8 production and secretion in response to S protein in PBMC and THP-1 cells and in HCoV-229E virus-infected PBMC. Activation and translocation of NF-κB was shown to occur rapidly following exposure of PBMC or THP-1 cells to S protein using a highly sensitive assay for active nuclear NF-κB p65 transcription factor. The results further suggested that released or secreted S protein could activate blood monocytes through recognition by toll-like receptor (TLR)2 ligand.
SARS coronavirus spike protein-induced innate immune response occurs via activation of the NF-κB pathway in human monocyte macrophages in vitro
https://www.sciencedirect.com/science/article/pii/S0168170209000124
So, it has been known that the Spike protein of SARS activates monocytes. Now, let’s look at a very recent (June 10th) study which definitively concluded that post-COVID there is a significant increase in hypertension those who become infected with COVID.
COVID-19 infection significantly increased the rate of incident HTN (main effects model HRR: 1.44 [95%CI: 1.32-1.57]; including interactions HRR: 2.05 [1.50-2.79]). If all individuals in our study had a COVID-19 infection, the 2-year cumulative risk of hypertension was 7.1% [5.7%-8.5%] versus 5.0% [4.2%-5.9%] if none had been infected. The largest absolute effects of COVID-19 on HTN incidence were in those with higher BMIs, higher pre-pandemic blood pressure levels and older ages. Our findings remained consistent with different definitions of the post-acute period and to confounding due to changes in HTN testing post-COVID.
COVID-19 Increases the Rate of Incident Hypertension: A Case-Control Cohort Time-to-Event Study
https://www.medrxiv.org/content/10.1101/2025.06.09.25329275v1.full-text
Here I propose that in addition to the Spike Protein’s activation of the Endothelium, its activation of Macrophages is a driving force behind initiating hypertension. M1 Macrophages, the type of Macrophage the Spike Protein polarizes Macrophages to, dominates the initiation/early stages of hypertension.
Macrophages are ubiquitous and universally present in all tissues. This includes the organ systems involved in essential hypertension: nervous, renal, and cardiovascular. Our understanding of macrophage biology and its role in hypertension, as well as other disease processes, is quickly advancing. The ability of macrophages to polarize into numerous phenotypes with functional versatility places them in the unique position to serve as mediators and agents between various tissues. It is clear that the basic elements involved in polarization of macrophages (such as NO, ROS, sodium balance, and regulation of T-lymphocytes) have direct applicability and relevance to the development of essential hypertension. It is also readily apparent that the influence of the “neuro-immuno” axis on macrophages is profound and also versatile. Our evidence indicates a possible model for the role of macrophages in the development of hypertension, demonstrating a critical role for their ability to “switch” between phenotypes, almost as if on a “time-release program”.
Thus, future studies should take into account the fact that although one phenotype, e.g. M1, dominates early in the course of the disease, another phenotype such as the M2 may dominate the later stages of a chronic disease process such as hypertension.
Macrophages Under Pressure: The Role of Macrophage Polarization in Hypertension
https://pmc.ncbi.nlm.nih.gov/articles/PMC5733698/
Additionally, monocytes, which transform into Macrophages, are critical for the initiation of hypertension.
The role of myelomonocytic cells appears to be critical for the initiation, progression and manifestation of arterial hypertension. Monocytes can induce vascular inflammation as well as tissue remodelling and (mal)adaptation by secreting chemokines and cytokines, producing ROS, expressing coagulation factors and transforming into macrophages.
Monocytes as immune targets in arterial hypertension
https://pmc.ncbi.nlm.nih.gov/articles/PMC6534790/
This is especially concerning as Spike from both virus and COVID vaccines have been shown to activate monocytes. Even for as long as 245 days post-vaccination.
Despite over 13 billion SARS-CoV-2 vaccine doses administered globally, persistent post-vaccination symptoms, termed post-COVID-19 vaccine syndrome (PCVS), resemble post-acute sequelae of COVID-19 (PASC). Symptoms like cardiac, vascular, and neurological issues often emerge shortly after vaccination and persist for months to years, mirroring PASC. We previously showed the S1 subunit of the SARS-CoV-2 spike protein persists in CD16+ monocytes after infection, potentially driving PASC. Approved vaccines (Pfizer, Moderna, Janssen, AstraZeneca) deliver synthetic S1 to elicit immunity, suggesting a shared mechanism. We hypothesized that vaccine-derived S1 persistence in CD16+ monocytes sustains inflammation akin to PASC, contributing to PCVS. We studied 50 individuals with PCVS symptoms lasting over 30 days post-vaccination and 26 asymptomatic controls, using (1) machine learning-based immune profiling to compare cytokine signatures with PASC, (2) flow cytometry to detect S1 in CD16+ monocytes, and (3) LC-MS to confirm S1 across vaccine types. We correlated S1 persistence with symptom duration and inflammation. Prior infection was excluded via clinical history, anti-nucleocapsid antibody tests, and T-detect assays, though definitive tests are lacking. Preliminary findings suggest S1 persistence in CD16+ monocytes and an associated inflammatory profile may contribute to PCVS.
Detection of S1 spike protein in CD16+ monocytes up to 245 days in SARS-CoV-2-negative post-COVID-19 vaccine syndrome (PCVS) individuals
https://pubmed.ncbi.nlm.nih.gov/40358138/
Looking at the Big Picture, what we begin to understand is that the Endothelial aspect of Spike Protein disease is just the beginning – the groundbreaking, if you will. Then, and this is what I am working on, it appears that Macrophages are recruited into tissue and organs to cause inflammation/organ damage. A disease of dual activations.
I will continue to search for mechanisms and therapeutics. It is an honor to have your readership, dialogue and support. Thank you, as always.