Posted on 04/28/2021 9:10:56 AM PDT by Red Badger
A new study from Washington University School of Medicine in St. Louis has identified a gene – called SVEP1 – that makes a protein that influences the risk of coronary artery disease independent of cholesterol. SVEP1 induces proliferation of vascular smooth muscle cells in the development of atherosclerosis. Shown is a stained section of atherosclerotic plaque from a mouse aorta, the largest artery in the body. Vascular smooth muscle cells are red; proliferating cells are cyan; nuclei of any cell are blue. Credit: In-Hyuk Jung, PhD, Stitziel Lab ================================================================
Independent of cholesterol, gene variants raise risk of heart disease, diabetes, high blood pressure.
High cholesterol is the most commonly understood cause of atherosclerosis, a hardening of the arteries that raises the risk of heart attack and stroke. But now, scientists at Washington University School of Medicine in St. Louis have identified a gene that likely plays a causal role in coronary artery disease independent of cholesterol levels. The gene also likely has roles in related cardiovascular diseases, including high blood pressure and diabetes.
The study was recently published in the journal Science Translational Medicine.
Studying mice and genetic data from people, the researchers found that the gene – called SVEP1 – makes a protein that drives the development of plaque in the arteries. In mice, animals missing one copy of SVEP1 had less plaque in the arteries than mice with both copies. The researchers also selectively reduced the protein in the arterial walls of mice, and this further reduced the risk of atherosclerosis.
Evaluating human genetic data, the researchers found that genetic variation influencing the levels of this protein in the body correlated with the risk of developing plaque in the arteries. Genetically determined high levels of the protein meant higher risk of plaque development and vice versa. Similarly, they found higher levels of the protein correlated with higher risk of diabetes and higher blood pressure readings.
“Cardiovascular disease remains the most common cause of death worldwide,” said cardiologist Nathan O. Stitziel, MD, PhD, an associate professor of medicine and of genetics. “A major goal of treatment for cardiovascular disease has appropriately been focused on lowering cholesterol levels. But there must be causes of cardiovascular disease that are not related to cholesterol – or lipids – in the blood. We can decrease cholesterol to very low levels, and some people still harbor residual risk of future coronary artery disease events. We’re trying to understand what else is going on, so we can improve that as well.”
This is not the first nonlipid gene identified that has been implicated in cardiovascular disease. But the exciting aspect of this discovery is that it lends itself better to developing future therapies, according to the investigators.
The researchers – including co-first authors In-Hyuk Jung, PhD, a staff scientist, and Jared S. Elenbaas, a doctoral student in Stitziel’s lab – further showed that this protein is a complex structural molecule and is manufactured by vascular smooth muscle cells, which are cells in the walls of blood vessels that contract and relax the vasculature. The protein was shown to drive inflammation in the plaques in the artery walls and to make the plaques less stable. Unstable plaque is particularly dangerous because it can break loose, leading to the formation of a blood clot, which can cause heart attack or stroke.
“In animal models, we found that the protein induced atherosclerosis and promoted unstable plaque,” Jung said. “We also saw that it increased the number of inflammatory immune cells in the plaque and decreased collagen, which serves a stabilizing function in plaques.”
According to Stitziel, other genes previously identified as raising the risk of cardiovascular disease independent of cholesterol appear to have widespread roles in the body and are therefore more likely to have far-reaching undesirable side effects if blocked in an effort to prevent cardiovascular disease. Although SVEP1 is required for early development of the embryo, eliminating the protein in adult mice did not appear to be detrimental, according to the researchers.
“The human genetic data showed a naturally occurring wide range of this protein in the general population, suggesting that we might be able to alter its levels in a safe way and potentially decrease coronary artery disease,” Elenbaas said.
Ongoing work in Stitziel’s group is focused on seeking ways to block the protein or reduce its levels in an effort to identify new compounds or possible treatments for coronary artery disease and, perhaps, high blood pressure and diabetes. The researchers have worked with Washington University’s Office of Technology Management (OTM) to file a patent for therapies that target the SVEP1 protein.
Reference: “SVEP1 is a human coronary artery disease locus that promotes atherosclerosis” by In-Hyuk Jung, Jared S. Elenbaas, Arturo Alisio, Katherine Santana, Erica P. Young, Chul Joo Kang, Puja Kachroo, Kory J. Lavine, Babak Razani, Robert P. Mecham and Nathan O. Stitziel, 24 March 2021, Science Translational Medicine. DOI: 10.1126/scitranslmed.abe0357
This work was supported in part by grants from the National Institutes of Health (NIH), grant numbers T32GM007200, T32HL134635, T32HL007081, R01HL53325, R01HL131961, UM1HG008853 and UL1TR002345; a career award from the National Lipid Association; and by The Foundation for Barnes-Jewish Hospital.
I think I’m one that has a genetic link. I’m not overweight. My cholesterol is terrible and I have plaque in my arteries. I exercise a lot too.
They were saying that transfats were bad for you, and that fat isn’t.
And that eating cholesterol isn’t a significant reason for high cholesterol.
There is a lot of quackery in certain branches of the natural health industry, but overall they have been right about a lot of the things they’ve warned against that modern medicine has advocated.
My husband’s grandmother had cholesterol in the upper 300’s and lived into her mid nineties.
I’ve been saying this for decades as a gut feeling. My cholesterol and triglycerides have been sky high since I was a teen. I had bad reactions to meds; finally said to hell with them. Now near 70, a stress test with contrast shows sound heart and clean arteries. Longevity runs on both sides of my family. Unfortunately, good knees don’t.
The anti-cholesterol jihad is modern medicine’s version of bloodletting.
As long as I don’t grow a 3rd arm from the back of my head... I’m ok with a bit of selective editing.
This would be a good start. CDF-8 expression, boosting brain power and memory retention, longevity... All on my list as well.
Article makes sense, since no one has been able to find an link between cholesterol levels and all-cause mortality.
Yet another scam exposed, at least for those of us willing to question what doctors and drug companies say.
Typo -— Should have been “GDF-8”. Growth Differentiation Factor 8. Limits the size of muscle growth. Belgian Blue cattle have this gene naturally mutated out.
More muscles and lower body fat... :-)
Well, my grandfather died of CVD at 50, my father is diabetic and has high cholesterol at 74, yet despite a brief round of statin meds on advice of a doctor I’ve since fired, I recovered my health/not overweight, take no pharmaceuticals whatsoever, get little exercise other than walking a mile or two for work, fought the virus & won and am 54 feeling better than I did when I was 30.
Make no assumptions.
Perhaps I’ll finish my books in a year or two which outline my experience & hypotheses, but that’s the limit as to health discussion I’ll have on FR (prior pledge; long story, short explanation).
Thank you for this. My new hero. I can't wait to get injected with some new innovative unproven DNA changing secret ingredients. Because this is labeled "experimental" they are automatically, by law, immune to liability lawsuits. They could kill everyone that takes their medicine and still be OK money wise. Money. That's the most important to me that they make money.
Neglected to mention:
My father had heart issues in the 90s around the same age as his father.
Yet I’m not worried.
SVEP1 induces hepatocellular carcinoma proliferation and metastasis
Have you tried a very low carb diet? Try it for at least thirty days. It may become a way of life.
Dietary fat is not the problem, it’s high blood sugar that inflames the arteries. They will heal, given the chance.
Cut out potatoes, rice, corn, wheat, etc. Anything that comes in a package with a label.
Limit carbs to 20 grams or less per day. No fruit, for a while anyway, then just a few berries per day if you must.
When you go low carb, you replace those calories with fat and protein. Eat meat, fish, eggs, dairy, some non starchy (above ground) vegetables if you want.
Don’t count calories. Eat when you’re hungry, stop when you are satisfied.
PING
Yes, please remove the SVEP1 from my system because atherosclerosis runs in the family.
.
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