Aspirin – a new drug for blood pressure, reversing heart disease (CVD) and aging?
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During the COVID hysteria, several studies came out showing that the morbidity and mortality of this conditions stems mostly from the ability of the SARS-CoV-2 spike protein to block the enzyme angiotensin converting enzyme (ACE) II. That enzyme converts the highly inflammatory protein angiotensin II back into the less inflammatory angiotensin I. Drugs that block the effects of angiotensin II at the receptor level or increase the activity of ACE II were found to be highly beneficial for COVID and it just so happens that they are also blockbuster blood pressure drugs. The most well-known such drug, used during COVID-19, was the drug losartan. It blocks the angiotensin II receptor type I (AT1R) and thus prevents angiotensin II from exerting its pro-inflammatory and blood pressure promoting effects. Losartan has been in clinical use for decades and recently has also been found to reverse aging of human cells by stimulating mitochondrial function. Thus, At1R drugs are the subject of many ongoing studies not only as potential treatments for COVID-type conditions, but also as disease-modifying therapies for CVD and aging in general. The study below demonstrates that humble aspirin has AT1R effects surprisingly similar to losartan and ameliorates various biomarkers of endothelial dysfunction, inflammation and degeneration. The mechanism of action of aspirin differs slightly from losartan. The former decreases the expression of AT1R, thus making the body less sensitive to the effect of angiotensin II, while the latter simply blocks the binding of angiotensin II with AT1R. However, the end effects are largely the same.
The concentration of aspirin used in the study was on the high end, achievable in humans with single bolus doses in the 1g-1.5g range. This dose range has also been shown in animal studies to retard and even reverse the progression of CVD, and those effects are not present at lower aspirin doses. So, it looks like aspirin’s benefits are dose-dependent and despite medicine telling us that there is no cure for CVD and that aspirin’s only benefits are related to blood clotting and requiring very tiny doses, the available evidence suggest that in higher doses aspirin may not only prevent heart attacks in people with already present CVD, but reverse said CVD altogether.
Finally, the study found that salicylic acid – the main metabolite of aspirin – also had the same effects, but required two-fold higher concentrations to produce the same benefit. That means a single dose of 2g-3g would be required if one were to use salicylic acid instead of aspirin.
https://pubmed.ncbi.nlm.nih.gov/22561363/
“…Previous studies have documented that Ang II, in low concentrations, stimulates formation of new capillaries from endothelium.[17] Atherosclerotic lesions express all components of
renin–angiotensin system, particularly AT1R.[24] The advancing atherosclerotic lesion contains large number of capillary channels (vasa vasorum), which are believed to contribute to the rupture of the plaque and result in acute ischemic syndromes.[25,26] AT1R activation, besides being a proangiogenic signal, is also a proinflammatory stimulus.[27] Accumulation of foam cells and immune cells and thin cap, probably as a result of release of matrix metalloproteinases (MMPs), are other key features of “vulnerable” plaque.[28–30] AT1R blocker therapy, with agents like losartan, reduces neovascularization and the atherosclerotic burden and modifies the molecular characteristics of advancing plaque.[31,32] Profibrotic effects of Ang II translate into fibrosis and reduction in compliance after tissue injury in animal models and in humans.[33–36] Upregulation of AT1R expression has been identified in aging arteries.37 It is interesting that ASA replicates many manifestations of AT1R blockade, such as stabilization of atherosclerotic plaque,[38] decrease in VEGF expression and subsequent angiogenesis,[6,39] and tissue fibrosis.[8] This study clearly demonstrates that treatment of endothelial cells with ASA in therapeutically achieved concentration is associated with reduction in NADPH oxidase–MAPK pathways and AT1R transcription. At the same time, there is inhibition of angiogenic effects of Ang II on endothelial biology, that is, formation of capillaries. It is conceivable that the effects of ASA on angiogenesis are related, at least in part to the reduction in NADP oxidase–MAPK pathways and AT1R transcription.”“…In essence, this study provides evidence that ASA treatment of endothelial cells results in a decrease in AT1R expression and capillary formation from endothelial cells. Reduction in capillary formation may be the basis for a antiatherosclerotic[40,41] and antiaging[42] effect of ASA. Because the effects of ASA were seen in therapeutically achieved concentrations, these data may be clinically relevant. Last, because the effects of SA were similar to those of ASA, it seems that it is the SA moiety that is responsible for the inhibitory effects of ASA on AT1R transcription.”