Tag: 22/2/24

Excessive Protein Consumption Increases Atherosclerosis Risk

Cardiovascular pitfalls to increasing protein intake discovered

Image by Scientific Animations, CC4.0

University of Pittsburgh School of Medicine researchers discovered a molecular mechanism by which excessive dietary protein could increase atherosclerosis risk. The study, published inĀ Nature Metabolism, combined small human trials with in vitro human and mouse cell experiments.

It showed that consuming over 22% of dietary calories from protein can lead to increased activation of immune cells that play a role in atherosclerotic plaque formation, driving the disease risk.

Furthermore, the scientists showed that one amino acid, leucine, seems to have a disproportionate role in driving the pathological pathways linked to atherosclerosis, or stiff, hardened arteries.

“Our study shows that dialling up your protein intake in pursuit of better metabolic health is not a panacea. You could be doing real damage to your arteries,” said senior and co-corresponding author Babak Razani, MD, PhD, professor of cardiology at Pitt.

“Our hope is that this research starts a conversation about ways of modifying diets in a precise manner that can influence body function at a molecular level and dampen disease risks.”

According to a survey of an average American diet over the last decade, Americans generally consume a lot of protein, mostly from animal sources.

Further, nearly a quarter of the population receives over 22% of all daily calories from protein alone.

That trend is likely driven by the popular idea that dietary protein is essential to healthy living, says Razani.

But his and other groups have shown that overreliance on protein may not be such a good thing for long-term health.

Following their 2020 research, in which Razani’s laboratory first showed that excess dietary protein increases atherosclerosis risk in mice, his next study in collaboration with Bettina Mittendorfer, PhD, a metabolism expert at the University of Missouri, Columbia, delved deeper into the potential mechanism and its relevance to the human body.

To arrive at the answer, Razani’s laboratory, led by first-authors Xiangyu Zhang, Ph.D., and Divya Kapoor, M.D., teamed up with Mittendorfer’s group to combine their expertise in cellular biology and metabolism and perform a series of experiments across various models, from cells to mice to humans.

“We have shown in our mechanistic studies that amino acids, which are really the building blocks of the protein, can trigger disease through specific signaling mechanisms and then also alter the metabolism of these cells,” Mittendorfer said.

“For instance, small immune cells in the vasculature called macrophages can trigger the development of atherosclerosis.”

Based on initial experiments in healthy human subjects to determine the timeline of immune cell activation following ingestion of protein-enriched meals, the researchers simulated similar conditions in mice and in human macrophages, immune cells that are shown to be particularly sensitive to amino acids derived from protein.

Their work showed that consuming more than 22% of daily dietary calories through protein can negatively affect macrophages that are responsible for clearing out cellular debris, leading to the accumulation of a “graveyard” of those cells inside the vessel walls and worsening of atherosclerotic plaques overtime.

Interestingly, the analysis of circulating amino acids showed that leucine, an amino acid enriched in animal-derived foods like beef, eggs and milk, is primarily responsible for abnormal macrophage activation and atherosclerosis risk, suggesting a potential avenue for further research on personalized diet modification, or “precision nutrition.”

Razani is careful to note that many questions remain to be answered, mainly: What happens when a person consumes between 15% of daily calories from protein as recommended by the USDA and 22% of daily calories from protein, and if there is a ‘sweet spot’ for maximising the benefits of protein (such as muscle gain) while avoiding kick-starting a molecular cascade of damaging events leading to cardiovascular disease.

The findings are particularly relevant in hospital settings, where nutritionists often recommend protein-rich foods for the sickest patients to preserve muscle mass and strength.

“Perhaps blindly increasing protein load is wrong,” Razani said.

“Instead, it’s important to look at the diet as a whole and suggest balanced meals that won’t inadvertently exacerbate cardiovascular conditions, especially in people at risk of heart disease and vessel disorders.”

Razani also notes that these findings suggest differences in leucine levels between diets enriched in plant and animal protein might explain the differences in their effect on cardiovascular and metabolic health.

“The potential for this type of mechanistic research to inform future dietary guidelines is quite exciting,” he said.

Source: University of Pittsburgh

Can Yoga Effectively Treat Chronic Back Pain?

Photo by Sasun Bughdaryan on Unsplash

New research published in theĀ Journal of Orthopaedic ResearchĀ suggests that the physical postures, breathing exercises, and mindfulness practices of yoga may benefit individuals with back pain.

In the study, 10 women with and 11 without chronic low back pain underwent an 8ā€session yoga program over 4 weeks, with the first session conducted in a clinic and the rest delivered with a teleā€approach. Women with chronic low back pain experienced a significant decrease in pain intensity, as assessed through a 10-point visual analogue scale (an average pain of 6.80 at the start, dropped to 3.30 after the sessions) and through a spine-related measure called the flexionā€“relaxation phenomenon, which is often absent or disrupted in people with low back painĀ  (5.12 at the start versus 9.49 after the sessions).

The findings suggest yoga can positively impact the neuromuscular response during trunk flexion and pain perception in individuals with chronic low back pain.

ā€œIt was interesting to show the role that yoga might play in the management of chronic back pain,ā€ said corresponding author Prof Alessandro de Sire, MD, of the University of Catanzaro ā€œMagna Graeciaā€ and University Hospital ā€œRenato Dulbecco,ā€ in Italy.

The authors noted that further research is warranted to assess yogaā€™s longā€term effects.

Source: Wiley

First HIV Antiretrovirals Manufactured in Space Delivered Back to Earth

For the first time, unique commercial pharmaceuticals produced using the zero gravity of outer space have been returned to Earth. After being stuck in space waiting for clearance to land, a capsule containing the small but extremely valuable cargo of HIV antiretrovirals landed in the desert in the US state of Utah. Drugs produced this way have higher purity and often improved pharmacokinetics, but have been too costly to produce until now.

In June 2023, a miniature pharmaceuticals factory built by Varda Space Industries was launched into Earth orbit. This small space startup company had only been around since 2020 ā€“ and the COVID pandemic had inspired them to look for a way to use the unique properties of space to directly benefit the health of people on Earth.

Zero gravity process can give drugs new properties

According to Varda co-founder Delian Asparouhov, gravity has significant effects somewhere between the microscopic scale and the atomic scale. This has beneficial applications in all manner of processes like crystal formation in drug manufacturing. For example, it is possible to give certain solid state pharmaceuticals improved solubility, turning a four-hour intravenous infusion into a couple of subcutaneous injections. The number of oral pills required for a treatment could be reduced. Since treatment compliance is a major obstacle to treatment, such improved drugs could significantly improve outcomes.

There are many drugs that were abandoned simply because administration was too impractical. Zero gravity manufacturing could open up these libraries of discarded drugs, Asparouhov says. It could also be possible to modify certain drugs to cross the bloodā€“brain barrier.

Antiviral Drug Polarized crystals (photographed through a microscope) of the drug 2-3 dideoxyadenosine, also known as ddA, a drug that is closely related to AZT or azidothymidine. The antiviral effect of ddA against HIV was discovered at the National Cancer Institute. Credit: Larry Ostby (Photographer), National Cancer Institute, National Institutes of Health

Onboard the small space factory is a pharmaceutical manufacturing system designed to produce ritonavir, an antiretroviral which was initially used to treat HIV. This early antiretroviral has a number of notorious gastrointestinal and metabolic side effects. In 1998, there was a major production crisis when it was discovered that were production defects in the the oral form stemming from crystallisation problems.

Nowadays, ritonavir has been surpassed by newer antiretroviral drugs for the treatment of HIV but has been investigated for cancer treatment and during the pandemic received emergency use authorisation for COVID treatment. The samples retrieved from the capsule will only be used for evaluation purposes, to help inform the production of other pharmaceuticals.

Producing drug proteins in space is nothing new. This has been done on space stations for decades ā€“ however, these were for research purposes in developing drugs and understanding biological processes. It is only now that technology has advanced to the point where it has become cheap enough to use the unique environment of outer space to manufacture high-value products.

The capsule with its onboard factory is specially designed to be recovered and reused to minimise costs. This has only been possible thanks to rockets becoming vastly cheaper. NASA’s space shuttle cost US$65 400 for each kilogram of cargo launched into space. Today, SpaceX’s Falcon 9 rocket costs a mere 4% of that, with costs set to fall further.

Such breakneck technological development was bound to run into a snag ā€“ this one consisting of red tape. The agency that regulates commercial air and spaceflight, the Federal Aviation Administration (FAA) gave Varda a licence for their payload to be launched, but not for the capsule to re-enter the atmosphere. The vast majority of satellites don’t have to worry about that, simply burning up in the atmosphere when they can no longer function. The FAA is obviously concerned about a large module returning intact but out of control.

Eventually, after more than six months of delays and looking at alternatives such as landing in Australia instead, Varda was able to secure a re-entry permit for 21st February and its capsule returned to Earth under a parachute in the Utah desert.

Asparouhov envisions a time when much larger orbital factories produce pharmaceuticals and other valuable materials in orbit.

Raised Blood Pressure is the Leading Risk Factor for Death in Australia

Hypertension has contributed at least 44% to CVD deaths over thirty years, more than dietary factors and tobacco

Raised blood pressure has been the leading risk factor for death in Australia for the past three decades, according to a study published February 21, 2024, in the open-access journal PLOS ONE led by Alta Schutte and Xiaoyue Xu from The George Institute for Global Health and UNSW, Sydney, with colleagues across Australia. It is also the main contributor to deaths from cardiovascular disease (CVD) specifically.

Raised blood pressure has long been recognized as a contributing factor to CVD and death, but is not always prioritized in national health plans. In this study, researchers focused on Australia, which lags behind other high-income countries in hypertension control. Data on how raised blood pressure compares to other risk factors for CVD burden ā€“ and how this changes over time ā€“ can help to guide public health agendas and inform the effectiveness of public health policies.

Researchers analysed epidemiologic data from the Global Burden of Disease (GBD) study between 1990 and 2019 to determine the leading risk factors associated with both all-cause and CVD deaths, over time and between gender and age groups. The GBD study provides data on nearly 400 diseases and 87 risk factors across 204 countries.

They found that while the contribution of raised blood pressure to these outcomes declined early in the study period (from around 54% to around 44%), it persisted as the leading risk factor for all-cause and CVD deaths. Dietary factors and tobacco use rounded out the top three risk factors. These findings strongly align with the recently established National Hypertension Taskforce of Australia, which aims to improve Australiaā€™s blood pressure control rates from 32% to 70% by 2030 (Hypertension – Australian Cardiovascular Alliance [ozheart.org]). The research findings further advocate for the prioritisation of blood pressure control on the public health agenda.

Differences by gender and age were also seen. For example, the contribution of raised blood pressure to stroke-related deaths in males aged 25ā€“49 years were higher than other age groups, exceeding 60% and increasing steeply over time.

The study reinforces the importance of blood pressure control and awareness. The researchers hope that the data will urge policymakers to prioritise blood pressure control efforts in Australia and will provide insight into age groups and populations that would benefit from more targeted action.

The authors add: ā€œThere is no doubt that raised blood pressure has remained the leading risk factor for all-cause and cardiovascular deaths in Australia across the past three decades. Our findings support actions to strengthen primary care and to improve the prevention, detection, treatment and control of raised blood pressure, with the goal of significantly reducing all-cause and cardiovascular deaths in Australia over the next decade.ā€

ā€œMoviesā€ with Colour and Music Visualise Brain Activity Data in Beautiful Detail

Novel toolkit translates neuroimaging data into audiovisual formats to aid interpretation

Simple audiovisualisation of wide field neural activity. Adapted from Thibodeaux et al., 2024,Ā PLOS ONE, CC-BY 4.0

Complex neuroimaging data can be explored through translation into an audiovisual format ā€“ a video with accompanying musical soundtrack ā€“ to help interpret what happens in the brain when performing certain behaviours. David Thibodeaux and colleagues at Columbia University, US, present this technique in the open-access journalĀ PLOS ONEĀ on February 21, 2024. Examples of these beautiful ā€œbrain moviesā€ are includedĀ below.

Recent technological advances have made it possible for multiple components of activity in the awake brain to be recorded in real time. Scientists can now observe, for instance, what happens in a mouseā€™s brain when it performs specific behaviours or receives a certain stimulus. However, such research produces large quantities of data that can be difficult to intuitively explore to gain insights into the biological mechanisms behind brain activity patterns.

Prior research has shown that some brain imaging data can be translated into audible representations. Building on such approaches, Thibodeaux and colleagues developed a flexible toolkit that enables translation of different types of brain imaging data ā€“ and accompanying video recordings of lab animal behaviour ā€“ into audiovisual representations.

The researchers then demonstrated the new technique in three different experimental settings, showing how audiovisual representations can be prepared with data from various brain imaging approaches, including 2D wide-field optical mapping (WFOM) and 3D swept confocally aligned planar excitation (SCAPE) microscopy.

The toolkit was applied to previously-collected WFOM data that detected both neural activity and brain blood flow changes in mice engaging in different behaviours, such as running or grooming. Neuronal data was represented by piano sounds that struck in time with spikes in brain activity, with the volume of each note indicating magnitude of activity and its pitch indicating the location in the brain where the activity occurred. Meanwhile, blood flow data were represented by violin sounds. The piano and violin sounds, played in real time, demonstrate the coupled relationship between neuronal activity and blood flow. Viewed alongside a video of the mouse, a viewer can discern which patterns of brain activity corresponded to different behaviours.

The authors note that their toolkit is not a substitute for quantitative analysis of neuroimaging data. Nonetheless, it could help scientists screen large datasets for patterns that might otherwise have gone unnoticed and are worth further analysis.

The authors add: ā€œListening to and seeing representations of [brain activity] data is an immersive experience that can tap into this capacity of ours to recognise and interpret patterns (consider the online security feature that asks you to ā€œselect traffic lights in this imageā€ ā€“ a challenge beyond most computers, but trivial for our brains)…[It] is almost impossible to watch and focus on both the time-varying [brain activity] data and the behavior video at the same time, our eyes will need to flick back and forth to see things that happen together. You generally need to continually replay clips over and over to be able to figure out what happened at a particular moment. Having an auditory representation of the data makes it much simpler to see (and hear) when things happen at the exact same time.ā€

  1. Audiovisualisation of neural activity from the dorsal surface of the thinned skull cortex of the awake mouse.
  2. Audiovisualisation of neural activity from the dorsal surface of the thinned skull cortex of the ketamine/xylazine anaesthetised mouse.
  3. Audiovisualisation of SCAPE microscopy data capturing calcium activity in apical dendrites in the awake mouse brain.
  4. Audiovisualisation of neural activity and blood flow from the dorsal surface of the thinned skull cortex of the awake mouse.

Video Credits:Ā ThibodeauxĀ et al., 2024,Ā PLOS ONE, CC-BY 4.0