Inflammation and the Stiffness of Blood Vessels

One of the ways in which major blood vessels decline in function with aging is that they lose their elasticity. The state of chronic inflammation that grows with aging contributes to this, as noted in this open access paper (in PDF format). This is probably connected to the fact that exercise helps improve the elasticity of arteries, given that exercise is shown to impact levels of inflammation: "Increased arterial stiffness is an independent predictor of cardiovascular disease independent from blood pressure. Recent studies have shed new light on the importance of inflammation on the pathogenesis of arterial stiffness. Arterial stiffness is associated with the increased activity of angiotensin II, which results in increased NADPH oxidase activity, reduced NO bioavailability and increased production of reactive oxygen species. Angiotensin II signaling activates matrix metalloproteinases (MMPs) which degrade TGFβ precursors to produce active TGFβ, which then results in increased arterial fibrosis. ... There is also ample clinical evidence that demonstrates the association of inflammation with increased arterial stiffness. Recent studies have shown that reductions in inflammation can reduce arterial stiffness. In patients with rheumatoid arthritis, increased aortic pulse wave velocity in patients was significantly reduced by anti tumor necrosis factor-α therapy. ... Thus, there is rationale for targeting specific inflammatory pathways involved in arterial stiffness in the development of future drugs. Understanding the role of inflammation in the pathogenesis of arterial stiffness is important to understanding the complex puzzle that is the pathophysiology of arterial stiffening and may be important for future development of novel treatments."



I think senescent cells are the primary driver of age-related chronic inflammation. The senescent adipocyte precursor phenotype is very pro-inflammatory. I wonder if the benefit of exercise in this case comes simply from depleting fat depots that would otherwise contain such noxious cells. Getting to the root cause by clearing out these cells seems like a good strategy, one for which immunotherapy might be particularly suited. If immunotherapy can work for cancer (which involves protean cells with unstable genotype and phenotype) then it can work all the better for these much less dysfunctional but still harmful cells, which can be gently nudged into apoptosis. Yes, I do note the irony of using the immune system to fight chronic inflammation.

Posted by: Jose at February 17th, 2012 1:30 PM
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