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Genetic Link to Clogged Arteries Discovered – Raises Risk of Heart Disease Independent of Cholesterol Levels
https://scitechdaily.com ^ | APRIL 27, 2021 | By WASHINGTON UNIVERSITY SCHOOL OF MEDICINE

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.


TOPICS: Business/Economy; Food; Health/Medicine; History
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1 posted on 04/28/2021 9:10:56 AM PDT by Red Badger
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To: Red Badger

Bookmark


2 posted on 04/28/2021 9:11:37 AM PDT by rdl6989 ( )
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To: All

I want my DNA changed and I want it now. I’ll live forever through better DNA.


3 posted on 04/28/2021 9:17:56 AM PDT by BipolarBob (Jeffrey Epsteins last words "I am not committing suicide".)
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To: Red Badger

As a dear cardiologist used to say: We can control the diet, we can control blood pressure and cholesterol with medications, but there isn’t a damn thing we can do about genetics.


4 posted on 04/28/2021 9:18:22 AM PDT by NautiNurse (It took 20 years for FL to clean up voter fraud in Broward and Palm Beach Counties. But we did it. )
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To: Red Badger

BTTT


5 posted on 04/28/2021 9:19:19 AM PDT by georgiabelle
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To: Red Badger

This may apply to some people with a family history of heart disease (genetics), but my smell detector senses a profit motive:

Take a pill/get a shot to prevent heart disease and change no behavior! /s

This, of course, ignores all the science which outlines an explosion in heart disease since the myopic Framingham Study was released and ultimately resulted in the lipid hypothesis/fat is bad proselytizing for >50 years.


6 posted on 04/28/2021 9:19:39 AM PDT by logi_cal869 (-cynicus the "concern troll" a/o 10/03/2018 /!i!! &@$%&*(@ -)
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To: logi_cal869

And once again, the natural health community is vindicated.

But I don’t expect anyone in the medical community to ever come close to acknowledging that.


7 posted on 04/28/2021 9:28:25 AM PDT by metmom (...fixing our eyes on Jesus, the Author and Perfecter of our faith....)
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To: Red Badger
"Independent of cholesterol, gene variants raise risk of heart disease, diabetes, high blood pressure."

I thought they already knew this. BTW, cholesterol is produced in the body and is the mother of all other hormones. It becomes problematic when the body ingests more than needed to function.

8 posted on 04/28/2021 9:36:09 AM PDT by A Navy Vet (USA Birth Certificate - 1787. Death Certificate - 2021 under Biteme.)
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To: logi_cal869

And the other pill pushers are not after profit.


9 posted on 04/28/2021 9:38:09 AM PDT by riverrunner
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To: metmom

How so? This study would suggest natural health is an equally ineffective approach.


10 posted on 04/28/2021 9:40:41 AM PDT by I-ambush (From the brightest star comes the blackest hole; you had so much to offer, did you offer your soul?)
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To: NautiNurse

“there isn’t a damn thing we can do about genetics.”

I could have told them that. My father and I had totally different life styles as far as diet and exercise. He died of a heart attack at 58, I had a heart attack at 59 that I survived after 11 minutes of CPR and two AED shocks. I agree, you can’t beat genetics.


11 posted on 04/28/2021 9:46:28 AM PDT by suthener
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To: Red Badger

We Jews have high cholesterol levels but live till our 80s.
I’ve told my Doc for years there is no way in heck I’m gonna take statins and I dont!


12 posted on 04/28/2021 9:47:36 AM PDT by Harpotoo (Being a socialist is a lot easier than having to WORK like the rest of US:-))
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To: Harpotoo

I used to take a statin but quit.....................


13 posted on 04/28/2021 9:55:14 AM PDT by Red Badger ("We've always been at war with Climate Change, Winston."..............................)
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To: NautiNurse

We can now. Gene replacement therapies.......................


14 posted on 04/28/2021 9:58:35 AM PDT by Red Badger ("We've always been at war with Climate Change, Winston."..............................)
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To: BipolarBob
Bob, meet Jim Greenwood. Be careful, he's got a history...

https://www.bio.org/events/bio-digital/announcements/recap-biotechs-finest-hour

Biotechnology is the most profound endeavor in human history. We are no longer controlled by our DNA. We are AT the controls. We are not simply the VICTIMS of disease, but the VICTORS over it. We are not limited by our genetics.

15 posted on 04/28/2021 10:01:22 AM PDT by MurrietaMadman (Keep in mind, the Gates of hell shall not prevail against you.)
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To: Harpotoo

As George Burns used to say, “I had a doctor................ He died.”..................


16 posted on 04/28/2021 10:01:33 AM PDT by Red Badger ("We've always been at war with Climate Change, Winston."..............................)
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To: Red Badger

“From this point on, if I take excellent care of myself — I’ll get very sick and die.” - Rodney Dangerfield


17 posted on 04/28/2021 10:02:52 AM PDT by dfwgator (Endut! Hoch Hech!)
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To: Red Badger

This article may well be inaccurate, because the scientific evedince is not there to support the cholesterol theory. Homocysteine is a better predicter of heart health.


18 posted on 04/28/2021 10:22:23 AM PDT by nickcarraway
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To: BipolarBob

IF you’ve received your covid vaccine, you already had your DNA changed.


19 posted on 04/28/2021 10:36:05 AM PDT by woodbutcher1963
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To: Red Badger

Me too.
I tried 5 different statins. They all gave me muscle aches to some degree. The last one the Dr tried to get me to take was an injection. I said: NOPE.


20 posted on 04/28/2021 10:40:02 AM PDT by woodbutcher1963
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