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
- Evinacumab Offers 'Remarkable' Lipid Lowering in Severe HoFHon October 12, 2020 at 8:16 am
Homozygous familial hypercholesterolemia patients with little or no LDL receptor activity had marked and sustained LDL cholesterol reductions with the antibody evinacumab, ELIPSE trial results show.
- Latest Research Evaluating VASCEPA® (Icosapent Ethyl) Mechanisms of Action Presented at European Atherosclerosis Society (EAS) Congress 2020on October 9, 2020 at 8:56 am
DUBLIN, Ireland and BRIDGEWATER, N.J., Oct. 05, 2020 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) today announced the presentation of new data at European Atherosclerosis Society (EAS) ...
- Vascular Proliferation and Atherosclerosis: New Perspectives and Therapeutic Strategieson October 8, 2020 at 5:00 pm
In atherosclerosis, the vascular smooth muscle cell (VSMC) contributes to vessel wall inflammation and lipoprotein retention, as well as to the formation of the fibrous cap that provides stability ...
- Sage Stallone died of heart attack, not drugs, coroner concludeson October 8, 2020 at 2:23 pm
died of atherosclerosis, which brought on a heart attack, a spokesman for the Los Angeles County coroner said Thursday. Stallone was found dead in his Los Angeles home on July 13 by his ...
- NILEMDO® significantly lowers cholesterol in people with familial hypercholesterolaemia shows new analysis presented at EAS 2020on October 8, 2020 at 12:00 am
Daiichi Sankyo Europe GmbH (hereafter, ‘Daiichi Sankyo’) today announced that NILEMDO ® (bempedoic acid) has demonstrated significant cholesterol reductions in people with the most common form of ...
- Latest Research Evaluating VASCEPA® (Icosapent Ethyl) Mechanisms of Action Presented at European Atherosclerosis Society (EAS) Congress 2020on October 5, 2020 at 8:29 am
DUBLIN, Ireland and BRIDGEWATER, N.J., Oct. 05, 2020 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) today announced the presentation of new data at European Atherosclerosis Society (EAS ...
- Latest Research Evaluating VASCEPA® (Icosapent Ethyl) Mechanisms of Action Presented at European Atherosclerosis Society (EAS) Congress 2020on October 5, 2020 at 4:06 am
today announced the presentation of new data at European Atherosclerosis Society (EAS) Congress 2020, being held virtually from October 4 – October 7, 2020 that add to the growing body of ...
- How hormone therapy slows progression of atherosclerosison October 1, 2020 at 6:22 am
Atherosclerosis is a chronic inflammatory process of blood vessels that is central to most cases of cardiovascular disease. (Unsplash) As one of the most common treatments for effectively managing ...
- Lipid metabolism controls lung cancer metastasis, not just diseases like atherosclerosison September 30, 2020 at 7:10 am
Most cancer deaths ultimately occur as a result of metastasis. Previous reports have demonstrated that fat tissue can provide energy support to the disseminated tumor cells that increases the survival ...
- Hormone Therapy Can Slow Down The Progression of Atherosclerosis in Menopausal Womenon September 29, 2020 at 9:01 pm
One of them is slowing the progression of atherosclerosis, a chronic inflammatory condition that causes cardiovascular diseases. Hormone therapy is a very common treatment to manage menopause ...
via Bing News