Statins Reduce Inflammation As Well As LDL

MedicalResearch.com Interview with:

Dr. Johan Frostegård MD PhD Professor of medicine Karolinska Institutet's Institute of Environmental Medicine and Consultant at Karolinska University Hospital's Emergency Clinic.

Dr. Johan Frostegård

Dr. Johan Frostegård MD PhD
Professor of medicine
Karolinska Institutet’s Institute of Environmental Medicine and
Consultant at Karolinska University Hospital’s Emergency Clinic

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Statins are one of the worlds most sold medications, which has generated large profits, but also, in my opinion, helped many people. Still, side effects are much discussed after more than 2 decades of use, as exemplified by a current debate between Lancet and BMJ (the former has the opinion that side effects are not major issues, but the latter do not agree). Also the exact role of LDL (low density lipoprotein, also known as the ”bad cholesterol”) as a risk factor is discussed, and can vary, according to many researchers. LDL levels are important among middle aged persons, especially men, as a risk markers for cardiovascular disease, especially myocardial infarction. LDL is most likely less important as a risk factor in individuals above 60 years of age, and also among women – as compared to middle aged men.


Pleiotropic effects, eg effects of statins, have been diccussed for long time and it is clear that inhibition of a pathway leading to prenylation (caused by inhibition of HMG CoA reductase) can lead to decreased activity of proinflammatory cytokines. Also immune effects have been discussed and reported, but these have been rather non-specific. We here demonstrate that statins (atorvastatin in focus, but simvastatin also tested) has specificl novel immunological effects, by inhibiting oxidized LDL-induced activation of T cells from atherosclerotic human plaques, and by inhibiting induction of atherogenic heat shock proteins. Oxidized LDL is likely to be a major player in atherosclerotic lesions, promoting immune activation and inflammation. Further, these effects were dependent on microRNA, of those tested the strongest was let7-c which is a tumor suppressor, induced by oxLDL. Statins abolished this induced tumor suppressor.

MedicalResearch.com: What should readers take away from your report?

Response: Statins were developed to decrease LDL-levels by inhibition of an enzyme central to cholesterol synthesis, namely HMG-CoA reductase and even though side effects are much discussed, they do decrease complications after myocardial infarction. However, the have other effects too, and we here describe a specific immunological one, which could be active directly in human atherosclerotic plaques. It is therefore possible that this (and other ”pleiotropic” effects not related to the original hypothesis with LDL-lowering, could be of major importance. In my opinion, this also implies that immune modulation in atherosclerosis actually works. During recent years it has become clear that atherosclerosis (and ensuing cardiovascular disease) is a chronic inflammatory condition, characterized by immune activation in the atherosclertotic plaques.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: One is to develop novel immune therapies against these diseases (atherosclerosis and cardiovascular disease). After all, statins were developed for a completely different reason, and it appears likely that novel immune therapies could improve treatment.

Another one is to look more in depth into cancer and statins. Recent large scale metastudies do not indicate that the risk of cancer is increased by statins, instead, they may even be protective. Still, there could be sub groups of cancer, perhaps let7-c dependent where statins still could be an issue. This deserves more studies.

MedicalResearch.com: Is there anything else you would like to add?

Response: Atherosclerosis and cardiovascular disease are the major causes of death and also of disease in the world, also nowadays in developing countries and is a field where novel immunological medications could add very much benefit to patients.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Johan Frostegård, Yong Zhang, Jitong Sun, Keqiang Yan, Anquan Liu. Oxidized Low‐Density Lipoprotein (OxLDL)–Treated Dendritic Cells Promote Activation of T Cells in Human Atherosclerotic Plaque and Blood, Which Is Repressed by Statins: microRNA let‐7c Is Integral to the Effect. Journal of the American Heart Association, 2016; 5 (9): e003976 DOI: 10.1161/JAHA.116.003976

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