Posted on 10/28/2009 7:21:09 PM PDT by TennesseeGirl
Inhibitors of HMG-CoA reductase (statins) are widely used medications for reduction of cholesterol levels. Statin use significantly reduces risk of cardiovascular disease but has also been associated with lower risk of other diseases and conditions, including dementia. However, some reports suggest that statins also have detrimental effects on the brain...
...Our data suggest that simvastatin and pravastatin differentially affect expression of genes involved in neurodegeneration and that statin-dependent gene expression regulation is cell type specific (excerpted)
(Excerpt) Read more at jlr.org ...
I have the same background. I keep telling my doctor that if my forebears lived into their 90’s without statins, then I won’t fix what’s not broken.
I totally agree!
(I think??)
Well, you know, I am interested, but there were too many unfamiliar words in there to catch my interest. Can you summarize it for a layman? tx
Must be that you understand your post, yet the unwashed have no idea what its about!
So I'll repost your article and hope that you can tell me:
1. What it means, and,
2. What it means"
Thanks! - a Simvastin client!
-------------------------------------------------------------------------------- Journal of Lipid Research, Vol. 50, 2095-2102, October 2009 Copyright © 2009 by American Society for Biochemistry and Molecular Biology
Differential effects of simvastatin and pravastatin on expression of Alzheimers disease-related genes in human astrocytes and neuronal cells Weijiang Dong1,*,, Simona Vuletic1,* and John J. Albers2,* * Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Department of Medicine, Seattle 98109, WA Xian Jiaotong University School of Medicine, Department of Human Anatomy and Histology and Embryology, Xian 710061, Peoples Republic of China
2 To whom correspondence should be addressed. e-mail: jja@u.washington.edu
Inhibitors of HMG-CoA reductase (statins) are widely used medications for reduction of cholesterol levels. Statin use significantly reduces risk of cardiovascular disease but has also been associated with lower risk of other diseases and conditions, including dementia. However, some reports suggest that statins also have detrimental effects on the brain. We provide evidence that simvastatin and pravastatin have significantly different effects on expression of genes related to neurodegeneration in astrocytes and neuroblastoma (SK-N-SH) cells in culture. Simvastatin significantly reduced expression of ABCA1 in astrocytes and neuroblastoma cells (by 79% and 97%, respectively; both P < 0.001). Pravastatin had a similar but attenuated effect on ABCA1 in astrocytes (54%, P < 0.001) and neuroblastoma cells (70%, P < 0.001). Simvastatin reduced expression of apolipoprotein E in astrocytes (P < 0.01). Furthermore, both statins reduced expression of microtubule-associated protein tau in astrocytes (P < 0.01), while both statins increased its expression in neuroblastoma cells (P < 0.01). In SK-N-SH cells, simvastatin significantly increased cyclin-dependent kinase 5 and glycogen synthase kinase 3β expression, while pravastatin increased amyloid precursor protein expression. Our data suggest that simvastatin and pravastatin differentially affect expression of genes involved in neurodegeneration and that statin-dependent gene expression regulation is cell type specific.Dong, W., S. Vuletic, and J. J. Albers. Differential effects of simvastatin and pravastatin on expression of Alzheimers disease-related genes in human astrocytes and neuronal cells.
Supplementary key words gene expression ATP binding cassette transporter A1 apolipoprotein E phospholipid transfer protein microtubule-associated protein tau amyloid precursor protein
Abbreviations: AD, Alzheimer's disease; apoE/APOE, apolipoprotein E; APP, amyloid precursor protein; BBB, blood-brain barrier; CDK5, cyclin-dependent kinase 5; CSF, cerebrospinal fluid; DAB1, Disabled 1; FPP, farnesyl pyrophosphate; GGPP, geranylgeranyl pyrophosphate; GSK3β, glycogen synthase kinase 3β; MAPT, microtubule-associated protein tau; PLTP, phospholipid transfer protein
Yeah. 65 is ancient.
I have high cholesterol and my pharmacist son told me that about half of those dying from heart attack or stroke don’t have high cholesterol, the other half do.
I chose not to take the statin drugs.
And that’s only if stroke doesn’t get you first.
I hope you read the other comments on this thread, doc.
http://www.sciencedaily.com/releases/2009/10/091028114017.htm
Albers and colleagues looked at the expression of genes related to neurodegeneration, and found that indeed, despite using biologically equivalent drug concentrations, differences were seen both between cells, and between drugs; for example, simvastatin reduced the expression of the cholesterol transporter ABCA1 by approximately 80% in astrocytes, while pravastatin lowered expression by only around 50%. Another interesting difference was that while both statins decreased expression of the Tau protein -associated with Alzheimer's disease -- in astrocytes, they increased Tau expression in neurons; pravastatin also increased the expression of another Alzheimer's hallmark, amyloid precursor protein (APP). While increased levels of these two proteins may account for potential risks of disease, Albers and colleagues also note that large decreases in cholesterol proteins like ABCA1 should be considered. Brain cholesterol levels tend to be reduced in elderly people, and in such individuals the long-term effects of statin therapy could lead to transient or permanent cognitive impairment.
Arrrggghhh — the important fact to me in all of this: “Brain cholesterol tends to reduce in older people.” I am going to ADD sausages to my diet, then. Brain trumps hiney. hahah.
Thanks for clarifying the research.
I am resisting statins too. And you are right — if it’s inherited, then look at the gene pool.
"This result could also have important implications for understanding recent data indicating that low cholesterol in brain cells has harmful effects on memory, concentration and mood. Twenty-five percent of cholesterol within the body is found in brain cells, where it seems to perform many important roles. Most of the theories for how cholesterol improves the function of brain cells have focused on its effect on the membranes that enclose these cells, but this work suggests that cholesterol may play a much more direct role by burying itself within some of the proteins that are necessary for cells to communicate." http://www.medicalnewstoday.com/articles/123346.php
(The study was performed by Brannigan, Henin and Michael L. Klein of the Center for Molecular Modeling in the Department of Chemistry at Penn as well as Richard Law of the Lawrence Livermore National Laboratory and Roderic Eckenhoff of the Department of Anesthesiology and Critical Care at the Penn School of Medicine. It was published in the Proceedings of the National Academy of Sciences. Funding for this research was provided by the National Institutes of Health and the National Science Foundation, with TeraGrid resources provided by the National Center for Supercomputing Applications. Source: Jordan Reese University of Pennsylvania)
I read the entire thread.
My response is that most doctors resort to cholesterol medicines because their patients won’t do the hard things to fix the problem themselves.
Most people refuse to take enough niacin to make a difference.
Most people refuse to work up a sweat for 45 minutes every day.
Most people refuse to swap out a few portions of dietary crap for vegetables.
Most people will not skip a few portions per day.
Most people won’t buy and take fish oil.
Most people want an easy fix for their problem.
For a small group, doing all of the right things doesn’t help enough and medication may be helpful and worth the risk of side effects.
For the largest group, they are taking the medicine because they don’t want to change their lifestyle and that largest group is placing themselves at risk of side effects which could be avoided.
65 Would be ancient for a user of statins....
And yet half the people who die of heart attacks have normal cholesterol. I would rather live with high cholesterol than blow my liver up with statin drugs.
And amen to that.
All true. But the assumption is statins are reducing the effects of other risky behaior. Not proven to my knowledge.
There are many studies showing benefit from the use of statins. The group that recieved the largest benefit are those that have already had an MI. Adding a statin decreased their subsequent death rate by 25%
Treating people before MI, there was always an ongoing argument about benefit, but 3 or 4 years ago, there was a big meta analysis released which showed decreased mortality from MI in those treated before their first MI, a couple of cancers and some other unexpected disease, I can’t recall at this time.
The meta analysis would cover a broad spectrum of people, so yes, there would appear to be benefit for people across a broad spectrum of behaviors. Especially since the number of people that will change their lifestyles without a major life changing event like an MI is extraordinarily small, the benefit would seem to cover those who are not making good choices.
I’m familar with the studies. I don’t trust them. These studies are influenced by similar drug companies that are not reporting MRSA infections in H1N1 cases, and over- reporting hotline calls as definite H1N1, to jack up support for the vaccine.
I think only about 10% of drugs on the market are necessary and worth the risk. Check out research on changes in the epigenome with ANY drug use.
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