Health UK (Commonwealth Union) – Researchers from the University of Aberdeen have showcased the continued efficacy of a previously identified drug known for its ability to ‘block’ fat within arteries. Building on a significant 2017 research paper conducted by the Aberdeen Cardiovascular and Diabetes Centre, and supported by the BHF, which revealed the potential of the drug Trodusquemine to counteract fat accumulation in the arteries of mice, the scientists have now published new findings demonstrating similar positive outcomes in human blood cells.
Researchers of the study stated that the initial pre-clinical tests indicated that administering Trodusquemine to mice on a high-fat diet inhibited the activity of an enzyme called PTP1B. This enzyme plays a role in the development of aortic plaque, a condition where fat accumulates in the artery wall. Elevated levels of PTP1B are commonly found in individuals with obesity, diabetes, and conditions characterized by prolonged inflammation, such as sepsis, inflamed diabetic foot ulcers, and allergic lung inflammation.
In the recent study, generously funded by the University of Aberdeen’s Development Trust, researchers evaluated the effectiveness of Trodusquemine on white blood cells obtained from 30 healthy volunteers and 30 volunteers diagnosed with coronary artery disease and atherosclerosis.
The researchers observed identical biochemical changes in human cells as those seen in mice when a PTP1B inhibitor was employed.
Elevated PTB1B levels trigger a cascade of events wherein white blood cells absorb oxidized cholesterol, transforming them into foamy cells. These foamy cells contribute to the formation of fatty deposits within arteries, exacerbating inflammation. Trodusquemine effectively thwarted this immune response, preventing white blood cells (macrophages) from transforming into foam cells. This mechanism likely underlies the drug’s ability to hinder the accumulation of fatty deposits.
Furthermore, the researchers noted that the genetic removal of PTP1B resulted in lowered cholesterol levels, particularly in low-density lipoprotein (LDL, or “bad” cholesterol), in mice. They also observed enhanced cell communication, a phenomenon typically suppressed in heart disease.
Professor Mirela Delibegovic, leading the study, indicated that their findings align with data presented in a previous publication from their lab, where either a single dose or chronic administration of Trodusquemine led to a reduction in aortic plaque in preclinical models.
Professor Delibegovic also indicated that it may represent a novel therapeutic technique to guard against atherosclerosis which is a condition that leads to a majority of heart attacks as well as strokes.
“Our initial study was cause for optimism but posed the question ‘is it feasible in humans and do the same changes occur’? Our findings here show the answer is an encouraging ‘yes’.
“We have been able to demonstrate that the drug works through the same mechanisms and reduces “bad” cholesterol so that the build-up of fatty streaks could potentially be overcome.
“This is an important step forward and proof of principle data we required to propose moving towards clinical trials.”
Professor James Leiper, Associate Medical Director at the British Heart Foundation, expressed satisfaction with the findings, pointing out that Atherosclerosis stands as a significant contributor to morbidity and mortality in the UK, being the primary cause of most heart attacks and strokes.
Professor Leiper, further indicated that the current study extends the groundwork laid by BHF-funded research, highlighting the role of PTP1B in atherosclerosis development in mice and establishing a similar role in white blood cells obtained from patients.
He further indicated that these findings pinpoint a potential novel therapeutic target for atherosclerosis treatment. He also pointed out that these results are promising, further research is imperative to validate the effectiveness of PTP1B inhibition in human subjects.
Enzymes play a key role in most biological functions and with the identification of the key role the PTP1B enzyme plays, it offers much promise to heart health.
