In animal studies, JH scientists have successfully prevented the development of atherosclerosis, the main cause of heart attacks and strokes and the number-one cause of death among humans
- Johns Hopkins scientists have halted the development of atherosclerotic heart disease in animals by blocking the activity of a sugar-and-fat molecule residing in the membranes of cells.
- Using a widely available man-made compound called D-PDMP, the researchers prevented the buildup of fatty plaque and calcium deposits inside the blood vessels of mice and rabbits fed a high-fat, cholesterol-laden diet.
- Treatment with D-PDMP appears to work by altering a range of biological glitches that affect the body’s ability to properly use, transport and purge itself of cholesterol — the fatty substance that accumulates inside vessels and fuels heart disease.
Working with mice and rabbits, Johns Hopkins scientists have found a way to block abnormal cholesterol production, transport and breakdown, successfully preventing the development of atherosclerosis, the main cause of heart attacks and strokes and the number-one cause of death among humans. The condition develops when fat builds inside blood vessels over time and renders them stiff, narrowed and hardened, greatly reducing their ability to feed oxygen-rich blood to the heart muscle and the brain.
In a series of experiments, described April 7 in the journal Circulation, the Johns Hopkins team says it identified and halted the action of a single molecular culprit responsible for a range of biological glitches that affect the body’s ability to properly use, transport and purge itself of cholesterol — the fatty substance that accumulates inside vessels and fuels heart disease.
The offender, the researchers say, is a fat-and-sugar molecule called glycosphingolipid, or GSL, which resides in the membranes of all cells, and is mostly known for regulating cell growth. Results of the experiments, the scientists say, reveal that this very same molecule also regulates the way the body handles cholesterol.
The Johns Hopkins team used an existing man-made compound called D-PDMP to block the synthesis of the GSL molecule, and by doing so, prevented the development of heart disease in mice and rabbits fed a high-fat, cholesterol-laden diet. The findings reveal that D-PDMP appears to work by interfering with a constellation of genetic pathways that regulate fat metabolism on multiple fronts — from the way cells derive and absorb cholesterol from food, to the way cholesterol is transported to tissues and organs and is then broken down by the liver and excreted from the body.
“Current cholesterol-lowering medications tackle the problem on a single front — either by blocking cholesterol synthesis or by preventing the body from absorbing too much of it,” says lead investigator Subroto Chatterjee, Ph.D., a cardio-metabolic expert at the Johns Hopkins Children’s Center. “But atherosclerosis is a multi-factorial problem that requires hitting the abnormal cholesterol cycle at many points. By inhibiting the synthesis of GSL, we believe we have achieved exactly that.”
Specifically, the experiments showed that treatment with D-PDMP led to:
- a drop in the animals’ levels of so-called bad cholesterol or low-density lipoprotein, LDL;
- a drop in oxidized LDL, a particularly virulent form of fat that forms when LDL encounters free radicals. Oxidized LDL easily sticks to the walls of blood vessels, where it ignites inflammation, damaging the vessel walls and promoting the growth of fatty plaque;
- a surge in good cholesterol or high-density lipoprotein, HDL, known to counteract the effects of LDL by mopping it up; and
- a significant drop in triglycerides, another type of plaque-building fat.
The treatment also prevented fatty plaque and calcium deposits from building up inside the animals’ vessels. These effects were observed in animals on a daily D-PDMP treatment even though they ate a diet made up of 20 percent triglycerides — the human equivalent of eating a greasy burger for breakfast, lunch and dinner. In addition, the researchers say, D-PDMP appears to precision-target the worst byproducts of aberrant cell growth signaling, such as oxidized LDL and the activity of certain chemicals that fuel vessel inflammation, without altering cell growth itself.
D-PDMP, which is already widely used in basic research to experimentally block and study cell growth and other basic cell functions, is deemed safe in animals, the investigators say. For example, animals in the current study had no side effects even when given D-PDMP doses 10 times higher than the minimum effective dose, the study found. The research team is currently designing a compound drug with D-PDMP, which they soon plan to test in other animals and, eventually, in humans.
Mice used in the experiments were genetically engineered to lack a protein essential in the breakdown of fats and thus were predisposed to atherosclerosis. The researchers fed the animals a high-fat diet over the course of several months, but also gave a third of the animals a low-dose of D-PDMP. They gave a double dose of the same inhibitor to another third and placebo to the rest.
When scientists measured the thickness of the animals’ aortas — the body’s largest vessel and one that carries blood from the heart to the rest of the body — they found striking differences among the groups. As expected, the aortas of mice that got placebo had grown thicker from the accumulation of fat and calcium deposits inside them. The aortas of mice on low-dose D-PDMP, however, were significantly thinner with little to no obstruction. To the researchers’ surprise, Chatterjee says, mice eating high-fat foods and treated with high-dose D-PDMP had nearly pristine arteries free of obstruction, indistinguishable from those of healthy mice.
The Latest on: Atherosclerosis
via Google News
The Latest on: Atherosclerosis
- Protein regulating inflammation in atherosclerosis identifiedon November 27, 2020 at 9:16 am
The protein CARD8 regulates several inflammatory proteins in people with atherosclerosis. This is shown in a new study by Örebro researchers published in the scientific journal Scientific Reports.
- CARD8 protein regulates inflammatory process in atherosclerosis, study showson November 26, 2020 at 3:22 pm
The protein CARD8 regulates several inflammatory proteins in people with atherosclerosis. This is shown in a new study by örebro researchers published in the scientific journal Scientific Reports.
- Association Between Clogged Arteries and Body Size Phenotype? Study Finds, “It Varies”on November 25, 2020 at 8:43 am
A recent study, published in The Journal of Clinical Endocrinology and Metabolism, sought to dive further into the impact of body size phenotypes on cardiovascular risk and effectively evaluate the ...
- White Supremacist Leader Tom Metzger Was Cremated, Riverside County Sayson November 24, 2020 at 2:41 pm
According to a death certificate for the notorious former KKK leader, he also suffered from atherosclerosis and anemia, which contributed to his passing in Hemet. The certificate — listing the d ...
- Pre-treating progenitor cells with protein-activator slows progression of atherosclerosison November 24, 2020 at 9:42 am
A new treatment for atherosclerosis, commonly known as hardening of the arteries, may be on the horizon, according to a study released today in STEM CELLS Translational Medicine (SCTM).
- Examining a Possible Link Between Atherosclerosis and Inflammationon November 19, 2020 at 2:36 pm
Unfortunately, this inflammation can damage the site even further, which occurs quite often in cardiovascular disease. Atherosclerosis is a cardiovascular disease that occurs when fats build up and ...
- Jose Ordovás, PhD, on Body Size and Its Effect on Subclinical Atherosclerosis Prevalenceon November 19, 2020 at 7:59 am
Body size affects the prevalence of subclinical atherosclerosis (SA), suggesting medication and other lifestyle changes could improve cardiac risk in those who fall into a riskier body-size category, ...
- Atherosclerosis: Symptoms, Causes, Treatment And Tips To Prevent by Dr Viveka Kumaron November 17, 2020 at 6:09 am
Atherosclerosis is a health problem that bothers many people. Know the causes, symptoms, treatment and tips to prevent from a cardiologist. Atherosclerosis is a very broad term which means that ...
- Tomocube’s HT-2 microscope quantifies therapeutic effects of targeted nanodrugs against atherosclerosison November 15, 2020 at 9:51 pm
Treatment of Atherosclerosis, the disease responsible for approximately half of all deaths in westernized societies, is a step closer following correlative studies using Tomocube’s HT-2 microscope.
- 15 Foods That May Help Prevent Clogged Arterieson November 15, 2020 at 4:00 pm
Atherosclerosis occurs when fatty deposits accumulate along artery walls. You may have heard the condition referred to as clogged arteries or a hardening of the arteries. This causes the arteries ...
via Bing News