A major cause of most coronary artery disease and the majority of ischemic stroke among humans is Atherosclerosis. Atherosclerosis is the process in which fatty acid deposits build up in the inner lining of arteries. Accumulation of fatty acid buildup results in a plaque that can significantly reduce blood flow and possibly even rupture. If they rupture they can cause blood clots to form which may block blood flow or travel to other parts of the body. Several studies suggest that there are several inflammatory mechanisms involved with the development and progression of Atherosclerosis. The cytokines IL-1 beta, IL-6 and TNF-alfa, nitric oxide synthase (NOS), cylcooxygenase-2 (COX-2) intrcelular adhesion molecule-1 (ICAM-1), matrix metalloproteinases, C-reactive protein and leukocytes are all involved with ischemic stroke. Studies suggest IL-6 and TNF alfa can have antiinflammatory, neuroprotective, and proinflammatory effects on ischemic stroke. Nitric oxide synthase produced early may be beneficial to vasodilation whereas if it is produced later may contribute to ischemic injury. Reactive oxygen species are a product of COX-2 reactions and are thought to increase tissue damage during cerebral ischemia. Adhesion molecules such as ICAM-1 are involved with leukocyte infiltration into the brain. Matrix metalloproteinases increase tissue damage and aide in the opening of the blood brain barrier. C-Reactive protein has received a lot of attention since its levels can be measured using a blood test and the protein levels increases during systemic inflammation. It is possible that this test can determine cardiovascular disease risk, and may help predict cardiovascular events such as heart attack and stroke. There are several studies which account for all of these inflammatory factors however little is still known of their actual effects on ischemic stroke. Some studies show the effects to be beneficial and some detrimental. What is known is that there seems to be a strong correlation with inflammation both before and after stroke, it is just unclear as to whether these processes are providing protective effects or further damaging cells and tissue.
Stroke also has a strong correlation with inflammatory conditions and infection. Studies have shown the bacteria Chlamydia pneumoniae may be a risk factor to stroke however it is still unclear. Chronic and recurrent respiratory infections, herpes viruses, periodontal disease and meningitis are just a few of the many conditions that may also cause an increased risk of ischemic stroke. Similar to the inflammatory factors and mechanisms of stroke, the connection of stroke to infections and inflammatory disorders is still unknown. Further scientific research is needed in the both of these areas to increase our knowledge and hopefully eliminate the numerous negative implications of stroke.
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Do you know if C-rp has any inflammatory (or anti-inflammatory) properties on it's own?
I think it is interesting that IL-6 and TNF-a are also major players in strokes. It seems we are learning that these two chemicals are more complicated than we think. They are involved in all inflammatory issues like diabetes and obesity.
CR-protein needs much more research before substantial questions can be answered. All in all, its presence in the bloodstream is associated with a handful of death sentences.
Hi, I'm Leslie Ritter, an "inflammation and stroke" researcher at the Univ. of Arizona. The information in review papers, such as this one, is hard to assimilate if you are not familiar with the field, but you summarized the content nicely--good job. I would like to comment on a couple of your statments, in order to (hopefully) clear up this massive amount of facts.
First, you commented on the fact that IL-6 and TNF alpha were thought to be anti-inflammatory, neuroprotective, and proinflammatory. Be careful--I think this statement is contradictory--are these molecules really thought to go both ways? Which is protective (anti-inflammatory) and which is harmful (proinflammatory)?
next, your comment re: CRP needs to be put in the context of acute injury (we know it is highly elevated in blood acute events like stroke and heart attack, thus its name as an "acute phase protein) or in the context of chronic conditions/injury. In this context, it has more recently been thought of as an additional indicator (not really a risk factor) of systemic inflammation. The highter the CRP, the higher the overall inflammation, and the "worse" the body may react to any innury, because of that inflammation.
Last, I think you said it just right--there is a strong correlation between inflammation before and after stroke. The "state" of the body's inflammation before a stroke may predict worse outcomes after stroke.
For example, we study the extent to which diabetes "inflames" blood leukocytes and platelets, and therfore makes stroke worse when it does happen.
Thanks again for the nice summary of a lot of years of research...because of this research, maybe one day we will actually "treat" specific inflammation pathways after stroke.
CRP is a most interesting part of this discussion. We (in our research group) have dabbled in some clinical research using a HMG Co-A reductase inhibitor (i.e.,"statins", such as Zocor) to investigate the acute effects (within days of administration) of these drugs on CRP levels. Our intent, of course, is to try and better understand how quickly we can intervene at the time of an acute event (and lower whole-body inflammation, as 'leslier' described). It is hard to tap into this arena of research since it is highly dominated by Paul Ridker and his colleagues (JessicaA: check the references in the review paper you read...I'm willing to bet the references are heavily populated by Ridker et al?). In fact, the CRP literature is so dominated by this group that some people have a conspiracy theory about CRP and the use of statins to lower it. (I don't have time to sit around pondering such theories, but hear about them now and then at meetings or when some big paper is published). However, I believe we do have much more to learn about CRP and its role in CVD and ischemic stroke. A very nice summary of a most complex body of literature. TLH,RN
what is the link to cholesterol synthesis and c-rp? Is this more about linking heart disease to cholerstol levels or can the use of statins directly decrease c-rp, TLH? I am interested to hear more about this.
From what I've read C reactive protein is a non-specific marker which means elevated levels do not necessarily indicate atherosclerosis or any other cardiovascular condition. CRP levels can rise in response to many things such as acute and chronic illness. Since it is not specific some believe it is not a good indicator of cholesterol or other risk factors of heart disease. Some studies indicate that measuring and decreasing both CRP and cholesterol would be beneficial to decrease heart disease and a low level of both of these factors may enhance statin therapy.
http://www.brighamandwomens.org/publicaffairs/Newsreleases/CRP_01_05_05.aspx
Here is the full link http://www.brighamandwomens.org/
publicaffairs
/Newsreleases/CRP_01_05_05.aspx
Davidm495 and Jessicaa495...great discussion on CRP. CRP is an independent predictor of acute coronary events. But Jessica is right...it is a non-specific indicator. So CRP rises for many reasons aside from CVD. If you looked at the Brigham and Women's site, then I'm sure you noticed that is where Paul Ridker et al. are based...and they believe very much in the potential of CRP to predict CVD events. So no...a high CRP does not mean you have high cholesterol (i.e., poor lipid panel), but a high CRP with poor lipids can be a sign of CVD. Davidm...you asked a good question. Let me think about that one. TLH
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