Publisher Health

Up to 60 percent of the risk associated with coronary arteriosclerosis may be explained by changes in the activity of hundreds of genes working together in networks across several organs in the body. Moreover, fat processing hormones may play a central role in coordinating this activity. That is the primary result of a study that began nearly 20 years ago on a hunch and involved hundreds of coronary artery disease patients from Northern Europe. The study was led by researchers at the Icahn School of Medicine at Mount Sinai.
“It is well known that coronary artery diseases are driven by metabolic disorders. Our results suggest that much of this relationship is best explained by a complex series of multi-organ gene regulatory networks that are reminiscent of the hub and spoke maps used to depict global airline traffic,” said Johan L.M. Bjorkegren, MD, PhD, Professor of Genetics and Genomic Sciences, and Medicine (Cardiology), and a senior author of the study published in Nature Cardiovascular Research. “We hope these network maps will give researchers the mechanistic framework needed to combat cardiovascular disease and develop more precise and personalized therapies.”
Coronary artery disease results from a set of metabolic disorders which cause cholesterol and other factors to build up and clog a person’s coronary arteries. This may lead to heart attacks or strokes. Affecting about 18.2 million Americans, coronary artery disease is the most common cause of heart disease in the United States. Risk factors, such as high cholesterol, high blood pressure, high blood sugar, and obesity, can involve a variety of organs. Although recent studies have shown that about 20 percent of the risk associated with this disease may be linked to slight differences in a person’s DNA sequences, very little is known about how these differences may alter gene activity to produce coronary artery disease.
To address this issue, researchers studied the gene activity across seven different tissues found in the body. Tissue samples were obtained from 850 Estonian patients during open breast surgery. The patients were part of the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study. Six hundred of the patients had coronary artery disease whereas the other 250 did not. Tissue samples were collected by researchers in the lab of Arno Ruusalepp, MD, PhD, who is chief vascular surgeon at the Tartu University Hospital in Estonia.
Gene activity was analyzed from the following tissue samples: blood, liver, skeletal muscle, visceral abdominal and subcutaneous fat, and two pieces of the arterial wall taken from different parts of the heart. Dr. Bjorkegren began the study more than 20 years ago when he was training as a heart surgeon.
“Back then I had a hunch. Advances in genome sequencing and the Human Genome Project offered researchers the promise to fully understand the biology behind complex disorders. Scientists were showing how these disorders can be linked to dozens of tiny DNA sequence differences, most of which are not part of any gene codes. Thus, we needed a way to understand how these tiny but numerous DNA differences may actually cause metabolic disorders and coronary artery disease. These patients provided a unique opportunity to bridge this knowledge gap by allowing my team to measure gene activity in disease-relevant organs throughout the body,” said Dr. Bjorkegren, who is also an associate professor at the Karolinska Institutet in Sweden.

A pioneering study has revealed how cellular compartments (organelles) are able to control how much they interact and cooperate.
The study, led by Professor Michael Schrader and Dr Joseph Costello from the University of Exeter, builds on their recent discovery of how two cell organelles — called peroxisomes and the endoplasmic reticulum (ER) — associate with each other and work together.
This cooperation is crucial for the production of specific lipids, which are essential for the function of nerve cells and can protect cells from oxidative damage.
Organelles are the functional units of a cell. Like organs in a body, they perform specialised functions.
To allow survival of the cell and organism, organelles have to interact and cooperate.
How this is mediated and regulated in the cell is an important and challenging question in cell biology.

That chewing food well makes a healthy eating habit is age-old wisdom. Slow eating and thorough chewing help prevent obesity and weight gain — a view popularized a century back and tested afterward in sporadic scientific studies. Typically, the chewing process reportedly enhances the energy expenditure associated with the metabolism of food and increases intestinal motility — all summing up to an increased heat generation in the body after food intake, known as diet-induced thermogenesis (DIT). However, how prolonged chewing induces DIT in the body remains unclear. Recently, Dr. Yuka Hamada and Professor Naoyuki Hayashi from Waseda University, Japan, have published a study that provides a causal link between chewing and DIT. The study has been published in the journal Scientific Reports.
DIT, also known as the thermic effect of food consumption, increases energy expenditure above the basal fasting level — a factor known to prevent weight gain. Earlier, the team found that slow eating and thorough chewing not only increased DIT but also enhanced blood circulation in the splanchnic region of the abdomen. Although these studies linked chewing-induced-DIT with increased digestion and absorption-related activity in the abdomen, they left scopes for further exploring a few crucial points. Hayashi explains, “We were unsure whether the size of the food bolus that entered the digestive tract contributed to the increase in DIT observed after slow eating. Also, do oral stimuli generated during prolonged chewing of food play any role in increasing DIT? To define slow chewing as an effective and scientific weight management strategy, we needed to look deeper into these aspects.”
To find the answers, the researchers designed their new study to exclude the effect of the food bolus by involving liquid food. The entire study included three trials conducted on different days. In the control trial, they asked the volunteers to swallow 20-mL liquid test food normally every 30 seconds. In the second trial, the volunteers kept the same test food in their mouth for 30 seconds without chewing, thereby allowing prolonged tasting before swallowing. Lastly, in the third trial they studied the effect of both chewing and tasting; the volunteers chewed the 20-mL test food for 30 seconds at a frequency of once per second and then swallowed it. The variables such as hunger and fullness, gas-exchange variables, DIT, and splanchnic circulation were duly measured before and after the test-drink consumption.
The results of this well-designed study turned up to be quite insightful. There was no difference in hunger and fullness scores among the trials. However, as Hayashi describes, “We found DIT or energy production increased after consuming a meal, and it increased with the duration of each taste stimulation and the duration of chewing. This means irrespective of the influence of the food bolus, oral stimuli, corresponding to the duration of tasting food in the mouth and the duration of chewing, increased DIT.” Gas exchange and protein oxidation too increased with the duration of taste stimulation and chewing, and so did blood flow in the splanchnic celiac artery. As this artery supplies blood to the digestive organs, the motility of the upper gastrointestinal tract also increased responding to oral stimuli during chewing.
The study highlighted that chewing well, by increasing energy expenditure, can indeed help prevent obesity and metabolic syndrome. Hayashi concludes, “While the difference in energy expenditure per meal is small, the cumulative effect gathered during multiple meals, taken over every day and 365 days a year, is substantial.”
Backed by robust science, slow eating and thorough chewing could be the latest recommendations for integration into our weight management efforts.
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There are myriad reasons why cancers develop. By studying genes which are altered in people with lymphoma, a multidisciplinary team of researchers, led by Charité — Universitätsmedizin Berlin and Goethe University Frankfurt, have identified a key mechanism involved in disease development. This signaling pathway, which the researchers describe in detail, controls the repair of DNA damage. Published in Nature Communications, these findings could open potential new avenues for treatment.
Cancer is associated with the disruption of various cellular signaling pathways. One of these pathways, ‘SUMOylation’, is responsible for the targeted modification of proteins, determining factors such as their lifespan and location within the cell. “As part of our study, we identified a previously unknown cancer gene, which controls this key cancer signaling pathway and could therefore offer a target for new cancer treatments,” says Prof. Dr. Ulrich Keller, Head of the Department of Hematology, Oncology and Cancer Immunology on Charité’s Campus Benjamin Franklin and Group Leader (Keller Lab) at the Max Delbrück Center for Molecular Medicine (MDC).
In an effort to identify and characterize these central control mechanisms, a team of researchers, led by Charité and Goethe University, systematically searched for genes which are found to be altered in lymphoma (cancer of the lymphatic system). Working with a mouse model, the researchers opted for a ‘transposon system’, a tool which utilizes mobile DNA segments (known as transposons or ‘jumping genes’) to randomly switch individual genes on and off in order to study their effects on tumor development. “Numerous large sequencing studies conducted over the past few years have produced detailed characterizations of cancer genomes, visualizing the complexity and heterogeneity of underlying modifications using ‘molecular maps’. However, these abnormalities often only occur in small groups of patients, rendering any interpretation of their significance more difficult,” explains first author Dr. Markus Schick, Team Leader and Principal Investigator at Charité’s Department of Hematology, Oncology and Cancer Immunology. He adds: “Our approach enabled us to identify many previously unknown cancer genes — among them the SENP6 gene, which is missing in approximately one third of all lymphoma patients. On the basis of this discovery, we then established the gene’s mechanism of operation and developed a treatment strategy.”
The gene’s role in cancer pathology had not previously been understood. SENP6, the protein encoded by this gene, removes SUMO modifications from other proteins inside the cell. By doing so, it also controls the proteins’ interactions with one another. The research team were able to prove that switching off SENP6 leads to cancer development, meaning it acts as a tumor suppressor. In healthy cells, SENP6 plays a key role in the repair of DNA damage. Loss of the gene results in this function being impaired. This leads to an accumulation of DNA damage which ultimately facilitates cancer development. In this study, however, the researchers were able to effectively suppress cancer growths following the loss of SENP6. They did so by inhibiting PARP, an enzyme involved in the repair of DNA damage, using drugs already licensed for breast cancer treatment. “Combining the biochemical expertise available at Frankfurt with the lymphoma and mouse genetics expertise at Charité in Berlin was key to the success of this project,” emphasizes Prof. Dr. Stefan Müller, whose research group at Goethe University’s Institute of Biochemistry II was involved in characterizing the SENP6 protein’s function.
Summarizing the research, Prof. Keller says: “Our findings enabled us to establish SENP6 as a biomarker for treatment success following PARP inhibitor therapy. We are currently investigating whether the mechanism described here might also be contributing to the development of cancers other than lymphoma.” He continues: “The aim of personalized medicine is to develop treatments which precisely match the specific needs of the individual patient. The next step, therefore, will be to conduct clinical studies to test whether these inhibitors offer an innovative, targeted treatment option in cancers characterized by the loss of SENP6. There is also the option of using them as part of combination therapy regimens, which are still too rarely used but hold enormous potential, particularly when they are selected based on an individual patient’s tumor biology.”
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Multiple myeloma is a cancer of the bone marrow, with a life expectancy of less than 5 years post-diagnosis. Proteasome inhibitors, the therapeutic backbone of current treatments, are very effective in treating newly diagnosed cancers but resistance or intolerance to these molecules inevitably develop, leading to relapses. While studying a neglected tropical disease, Buruli ulcer, researchers from the Institut Pasteur and Inserm discovered a novel therapeutic target for multiple myeloma that could allow to bypass this resistance. The results of this study were published in EMBO Molecular Medicine on January 11th, 2022.
Multiple myeloma is a cancer caused by the abnormal proliferation of plasma cells, white blood cells producing antibodies, in the bone marrow. Scientists from the Institut Pasteur and Inserm, in collaboration with the University of Paris and the Saint Louis Hospital (AP-HP) describe a new mechanism to selectively kill these cancer cells.
Researchers in the Immunobiology of Infection Unit at the Institut Pasteur made this discovery while working on a completely different disease: Buruli ulcer. This neglected tropical disease, caused by infection with a bacterium (Mycobacterium ulcerans), can provoke severe and irreversible skin necrosis. Lesions are due to bacterial production of a toxin called “mycolactone” in infected skin. In 2016, this team discovered how mycolactone causes the clinical manifestations of Buruli ulcer: by targeting the translocon (Sec61).
The translocon is a channel anchored in the wall of a cell compartment called the endoplasmic reticulum that plays a crucial role in the synthesis of a subset of proteins: those that are destined to be secreted in the extracellular medium. The translocon controls the import of these proteins into the endoplasmic reticulum, and it is the main gateway to the secretory pathway. By blocking Sec61, mycolactone retains these proteins inside the cell and provokes their degradation by the proteasome, a stressful process that can evolve towards programmed cell death.
Using murine models and tumors from patient biopsies, researchers demonstrated that mycolactone is highly toxic to multiple myeloma cells, including those that have become resistant to proteasome inhibitors, at doses that are non-toxic to normal cells. In addition, they showed that mycolactone and proteasome inhibitors work in synergy, mutually potentiating their anti-cancer effects.
“This study provides the proof of concept that the translocon is a new therapeutic target in multiple myeloma. The next step will be to identify drug-like molecules inhibiting Sec61, which could constitute a new treatment for this cancer. In addition, we aim to study whether this target could be common to other cancers.” explains Caroline Demangel, head of the Immunobiology of Infection Unit at the Institut Pasteur.
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Even older fruit flies are adept at evading a fly swatter.
Biologists at the University of Iowa pinpointed how fruit flies — no matter their age — maintained neural circuits for certain motor functions, while losing their edge in other performance measures.
The biologists looked at how well individual neurons and neural circuits function as flies age and when they are subjected to stressors such as changes in temperature and an erosion in protective anti-oxidants in their bodies. They identified biomarkers of aging in the electrical performance of specific motor circuits, separating circuits that weakened as flies aged to those that remained the same no matter the fly’s age.
One of the “aging-resilient circuits,” the biologists found, was in the fly’s ability to escape danger (such as a fly swatter).
On the other hand, flies’ muscle activity during flight and the neural circuits recruited during seizures weakened as they got older.
“Our identification of aging ‘landmarks’ in motor circuit function will help future studies in uncovering genetic pathways or environmental factors contributing to healthy aging in the brain as well as age-related neurodegeneration,” says Atulya Iyengar, post-doctoral researcher in the Department of Biology and a researcher with the Iowa Neuroscience Institute.
The study is titled, “Distinct aging-vulnerable and -resilient trajectories of specific motor circuit functions in oxidation- and temperature-stressed Drosophila.” It was published online on Dec. 7 in the journal eNeuro.
Iyengar is first author on the study. Chun-Fang Wu, professor in the Department of Biology, is the study’s corresponding author. Hongyu Ruan, formerly at Iowa and now assistant professor at SUNY Upstate Medical University, is co-first author.
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Materials provided by University of Iowa. Original written by Richard Lewis. Note: Content may be edited for style and length.

Long before the onset of dementia, there is evidence for increased activity of the brain’s immune system. Researchers from DZNE and the University Hospital Bonn (UKB) come to this conclusion based on a study of more than 1,000 older adults. To this end, various proteins were measured in the cerebrospinal fluid: They served as so-called biomarkers that indicate inflammatory processes of the nervous system. As it turned out, some of these molecules seem to be part of a damage control program of the immune system, which could be useful for the development of new drugs. The study results have been published in the scientific journal Neuron.
In recent years, it has become evident that the brain’s immune system and related inflammatory processes — also known as “neuroinflammation” — significantly contribute to the development of Alzheimer’s disease. In view of this, the scientists analyzed various immunological biomarkers that are characterized by good detectability in the cerebrospinal fluid and reproducible results. “It was already known that these markers indicate immune processes in the context of Alzheimer’s disease. However, how these markers relate to brain volume, cognitive performance and other parameters had not been studied as comprehensively as we have now,” explains Prof. Michael Heneka, who led the current study during his long-time tenure at DZNE and UKB. Since the beginning of this year, he has been director of the Luxembourg Centre for Systems Biomedicine.
“We have found that some of these inflammatory markers are conspicuous even when there are no symptoms of dementia yet,” Heneka says. “Based on the data we have so far, we can’t specify the lead time at this point. But my estimate is that it is at least ten to twenty years.”
Extensive Database
The starting point for the investigations were data from the so-called DELCODE study, in which the DZNE researches dementia and its preliminary stage in collaboration with several university hospitals across Germany. The current study project included findings from around 300 women and men, all over the age of 60. This group comprised cognitively normal adults, individuals with memory problems of varying degrees of severity and also people with dementia of the Alzheimer’s type. Samples of cerebrospinal fluid and standardized memory tests were available from all study participants, and magnetic resonance images of the brain were taken from most of them. For each study participant, the data included the baseline examination and at least one follow-up one year later. For some subjects, findings spanned multiple follow-ups over a period of up to five years.
Striking Even Without Dementia
“There are established biomarkers for amyloid and tau. These are proteins that accumulate in the brain in Alzheimer’s disease and can also be detected in the cerebrospinal fluid. Their levels usually change even before symptoms of dementia arise, which is considered a sign of processes for neuronal damage. We wanted to know whether inflammatory markers respond in a similar way,” says Dr. Frederic Brosseron, a scientist at DZNE and one of the first authors of the current publication in “Neuron.” “In fact, we found that most inflammatory markers are elevated, especially when a marker for neuronal damage is elevated. This applies even when these individuals do not yet show symptoms of dementia. Thus, the inflammatory markers we recorded are particularly useful for studying neuroinflammation at early stages of disease.”
Evidence for Neuroprotection
Two of these markers in particular — proteins belonging to the “TAM receptor family” — seem to be linked to a damage control program. In study participants with particularly levels of these high markers, brain volume was comparatively large and cognitive functions declined more slowly over time. To verify these findings, Heneka’s team evaluated data from a study cohort of ACE Alzheimer Center Barcelona with more than 700 adults, must of them with mild cognitive impairment. This analysis confirmed the results from the DELCODE study were.
“Inflammatory processes are not bad per se, but rather a normal, protective reaction of the immune system to threatening stimuli, especially at the beginning. But they should not last too long, therefore they need to be regulated,” says Heneka. TAM family proteins are known to influence immune responses and promote disposal of cellular waste, he explains. “Supporting this protective function would be an interesting approach for pharmaceutical research. This is where I see potential for application of the markers we have identified. For the early detection of dementia in routine care, measuring these markers is too complex. But when testing new drugs in clinical trials, there are other technical options. In trials, indicators are needed to assess whether interventions are working and whether tested drugs are effective. The TAM markers could be very useful for this.”
This research was supported in part by funding from the international PREADAPT project, which is funded by the EU Joint Programme — Neurodegenerative Disease Research (JPND).

Certain brain wave patterns that occur while an individual sleeps may be assessed by clinicians to help them diagnose dementia and other conditions related to memory, language, and thinking. A new study published in Sleep that was led by investigators at Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center (BIDMC) could help improve automated methods for detecting these brain wave patterns, or sleep spindles, and for correlating them with cognitive function.
Sleep spindles are bursts of brain activity that occur during non-REM sleep and can be assessed through electroencephalograms (EECs) involving non-invasive electrodes placed on the scalp. Spindles are considered a “fingerprint” that vary among individuals, are highly heritable, and tend to be consistent from night to night.
“With the rising burden of neurodegenerative disease, there is a pressing need for a sensitive biomarker of cognition. This has led to a surge of research examining sleep spindles, an oscillatory pattern of brain activity observed during sleep, and their role in various neuropsychiatric conditions and cognitive performance,” says lead author Noor Adra, a clinical research coordinator at MGH.
Although sleep spindles and other brain features represent promising potential electrophysiologic markers of neurodegenerative and psychiatric diseases, detecting and assessing sleep spindles is not straightforward. “People have already known that these transient high frequency events during sleep in the brain are closely linked to cognition, especially to learning and memory. But when you try to detect spindles among more than 100 sleep recordings, things become less clear — such as what is the best threshold, what is the best minimum duration, etc.,” says co-author Haoqi Sun, PhD, an investigator in the department of Neurology at MGH.
Sleep spindles are typically analyzed through visual inspection of EEGs, but automated methods can offer more consistent results. No consensus exists for parameters for such automated methods, however.
To address these issues, the investigators designed sleep-related experiments involving 167 adults to characterize how spindle detection parameter settings influence the association between spindle features and cognition and identified parameters that best correlate with cognitive performance.
The team also found that sleep spindles were most strongly linked with what’s known as fluid intelligence, which relies on abstract thinking and problem-solving skills and declines during early stages of dementia. “Therefore, our findings support sleep spindles as a sleep-based biomarker of fluid cognition,” says Adra. “By optimizing the detection of this proposed sleep-based biomarker of cognition, we hope to guide future studies that examine the sensitivity of this biomarker in neurodegenerative populations.”
“Sleep spindles are one among many important measurable features of brain activity during sleep that provide a window into the brain’s current state of health and individuals’ risk for developing brain disease or cognitive decline. Now that we better understand how to measure sleep spindles, we can add these into a growing arsenal of brain health indicators that can be measured during sleep,” adds co-senior author M. Brandon Westover, MD, PhD, an investigator in the department of Neurology at MGH and director of Data Science at the MGH McCance Center for Brain Health. “These indicators will be essential tools in our quest to develop treatments that can preserve and enhance brain heath.”
Co-authors include Wolfgang Ganglberger, Elissa M. Ye, Lisa W. Dümmer, Ryan A. Tesh, Mike Westmeijer, Madalena Da Silva Cardoso, Erin Kitchener, An Ouyang, Joel Salinas, Jonathan Rosand, Sydney S. Cash, and Robert J. Thomas.
The study was funded by the Glenn Foundation for Medical Research, the American Federation for Aging Research, the National Institutes of Health, and the American Academy of Sleep Medicine.

From our first breath, our lungs are exposed to microorganisms, such as bacteria and viruses. Thanks to immune cells in the lungs, so-called macrophages, we are protected from most infections at an early age. In a new study published in the Journal of Experimental Medicine, researchers from Karolinska Institutet show how lung macrophages develop; new findings that can help to reduce organ damage and that are significant for the continued development of important lung disease treatments.
Lung macrophages begin to develop in humans from birth when the lungs are first inflated with inhaled air. Despite the importance of lung macrophages in the immune system, it has not been previously known how they develop in humans, since in-vivo studies in humans are difficult to conduct.
However, with the help of a model, researchers at Karolinska Institutet have now been able to directly study the development of human macrophages in a living lung. In the study, it was discovered that lung macrophages develop in two different ways.
“In the first type of development, lung macrophages originate from precursor cells that are already present in the fetus’ liver,” says Tim Willinger, associate professor at the Department of Medicine, Huddinge, Karolinska Institutet, who has led the study. “After we are born, these precursor cells move from the liver to the lungs via the bloodstream. In the lungs, they are then exposed to various growth factors, which helps them to develop into ‘mature’ lung macrophages. The second type of development occurs later in life. At that point they develop from adult precursor cells, so-called monocytes, which are found in the blood.”
Similar gene expression but different functions
The researchers also investigated whether the origin of the lung macrophages affects their function. Here they could see that the lung macrophages, regardless of their origin, had a similar gene expression but with different functions.
“We discovered that fetal precursor cells divide faster than the adult precursor cells,” says the study’s first author Elza Evren, doctoral student in Tim Willinger’s research group. “The fetal precursor cells therefore populate the lungs faster, which is important early on in life to quickly remove microorganisms and other inhaled particles.”
The lung macrophages derived from adult precursor cells were instead found to be strongly activated by interferon, a protein that has the task to defend against viral infections. It is therefore very likely that this particular type of lung macrophage has an important function within the immune system to help fight viruses.
The researchers were also able to see that these lung macrophages are similar to pro-inflammatory macrophages, which can become overactivated and contribute to serious lung damage in diseases such as COVID-19.
Limit lung damage and promote new treatments
The new findings contribute to a better understanding of the origin and function of lung macrophages. The human fetal progenitor cell that the researchers have identified is a potential cell that can be targeted to regenerate tissue-protective macrophages, limit organ damage and promote tissue repair in an injured lung. These findings can also support the development of new treatments for a number of lung diseases.
The study was supported by grants from Swedish Research Council, SciLifeLab, Knut and Alice Wallenberg Foundation, Karolinska Institutet, Centre for Innovative Medicine (CIMED), Region Stockholm, the Swedish Heart-Lung Foundation, Petrus och Augusta Hedlunds Stiftelse and the Royal Swedish Academy of Sciences. One of the authors from Yale University has reported conflicts of interest, which are described in detail in the scientific paper.
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New kidney research from the University of Virginia School of Medicine is raising concerns that long-term use of drugs commonly prescribed to treat high-blood pressure and heart failure could be contributing to kidney damage.
Patients should continue taking the medications, which include the well-known and widely used ACE inhibitors, the researchers say. But the scientists are urging studies to better understand the drugs’ long-term effects.
“Our studies show that renin-producing cells are responsible for the damage. We are now focusing on understanding how these cells, which are so important to defend us from drops in blood pressure and maintain our well-being, undergo such transformation and induce kidney damage,” said Maria Luisa Sequeira Lopez MD, of UVA’s Department of Pediatrics and Child Health Research Center. “What is needed is to identify what substances these cells make that lead to uncontrolled vessel growth.”
The Causes of Kidney Damage
Chronic high blood pressure affects a billion people around the world. The UVA researchers wanted to better understand why severe forms of the condition are often accompanied by thickening of the arteries and small blood vessels in the kidney, leading to organ damage.
They found that specialized kidney cells called renin cells play an important role. These cells normally produce renin, a vital hormone that helps the body regulate blood pressure. But harmful changes in the renin cells can cause the cells to invade the walls of the kidney’s blood vessels. The renin cells then trigger a buildup of another cell type, smooth muscle cells, that cause the vessels to thicken and stiffen. The result: Blood can’t flow through the kidney as it should.
Further, the researchers found, long-term use of drugs that inhibit the renin-angiotensin system, such as ACE inhibitors, or angiotensin receptor blockers, have a similar effect. These drugs are widely used for many purposes, including treating high blood pressure, congestive heart failure and heart attacks, as well as to prevent major heart problems. But long-term use of the drugs was associated with hardened kidney vessels in both lab mice and humans, the scientists found.
The researchers note that the medications can be lifesaving for patients, so they stress the importance of continuing to take them. But they say additional studies are needed to better understand the drugs’ long-term effects on the kidneys.
“It would be important to conduct prospective, randomized controlled studies to determine the extent of functional and tissue damage in patients taking medications for blood pressure control,” said Ariel Gomez, MD, of UVA’s Department of Pediatrics and Child Health Research Center. “It is imperative to find out what molecules these cells make so that we can counteract them to prevent the damage while the hypertension is treated with the current drugs available today.”
Findings Published
The researchers have published their findings in the scientific journal JCI Insight. The article was selected as a cover story. The research team consisted of Hirofumi Watanabe, Alexandre G. Martini, Evan A. Brown, Xiuyin Liang, Silvia Medrano, Shin Goto, Ichiei Narita, Lois J. Arend, Sequeira-Lopez and Gomez.
The research was supported by the National Institutes of Health, grants P50 DK 096373, R01 DK 116718, R01 DK 116196, R01 DK 096373 and R01 HL 148044; and the Japan Society for the Promotion of Science Overseas Research Fellowships.