Preprint Shear Stress Tolerance Threshold, eNOS Uncoupling, and the Two-Threshold Model of [PEM] in [LC]: A Mechanistic Hypothesis [...], 2026, Karipidis et al

[Violeta]

I see that laminar stress and oscillatory shear stress include the topics of senescence, autophagy, and STING.

Oscillatory shear stress promotes atherosclerosis via inducing STING activation. Activation of STING pathway induces endothelial cell senescence in atherosclerosis. Oscillatory shear stress mediating STING activation via mitochondrial DNA leakage.

In this study, we found that laminar shear stress(LSS) could inhibit the increased expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and matrix metallopeptidase-9 (MMP-9) caused by TNF-α in an autophagy-dependent pathway in human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs). Whole-transcriptome sequencing analysis revealed that erythropoietin-producing hepatocyte receptor B2 (EPHB2) was a key gene in response to LSS. Moreover, co-immunoprecipitation assay indicated that LSS could enhance the EPHB2-mediated nuclear translocation of high mobility group box-1 (HMGB1), which interacts with Beclin-1 (BECN1) and finally leads to autophagy.

This tangent is interesting.
Oh, it's not a tangent! Senescence may be part of the vicious cycle.

Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS​

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[Violeta]

A new study supported by PolyBio Research Foundation studied children and young adults with Long COVID, providing evidence linking endovascular inflammation, increased quantity and size of fibrin-amyloid “microclots,” and neutrophil activation, and finding detectable Spike protein in a subset. Published in Pediatric Research, the study helps clarify the biological basis of cardiovascular symptoms in an important but understudied Long COVID population, and advances scientific insights that will support future diagnostic development.

It seems it would be helpful to combine polybio's markers and @YiannisK's.

https://polybio.org/new-study-polybio-supported-study-identifies-microclots-endothelial-injury-markers-and-neutrophil-activation-in-children-and-young-adults-with-long-covid/

 

[Violeta]

I really appreciate that @YiannisK's paper includes recommendations for remediation.



I have heard good things about Sulodexide for repairing glycocalyx. It's not available in the States yet, but fucoidan could be used in it's place.

Here's a study about SARS-CoV-2 effect on glycocalyx.

Endothelial Glycocalyx Injury in SARS-CoV-2 Infection: Molecular Mechanisms and Potential Targeted Therapy​

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