Promising way to cut atherosclerotic plaque

A new study shows targeting a protein in smooth muscle cells can block and decrease the buildup of atherosclerotic plaque in mouse models. Atherosclerosis is a common condition that develops when plaque builds up inside the arteries. Diseases linked to atherosclerosis, such as coronary artery disease, are the leading cause of death in the United States. Atherosclerosis can affect most of the arteries in the body, including arteries in the heart, brain, arms, legs, pelvis, and kidneys. Researchers have been focused on other cell types, like endothelial cells and macrophages, but more recent studies have highlighted a role of smooth muscle cells in plaque formation. Using a knockout method, researchers fed genetically modified mice a high fat diet and caused the mice to have high cholesterol levels in their blood to drive atherosclerotic plaque formation. Blocking a specific protein called PERK in these mice resulted in an 80% decrease of atherosclerotic plaque buildup in male mice. Males tend to have more of this buildup than females. This tells us that blocking PERK in smooth muscle cells is important in plaque formation. Interestingly, this protein is activated in smooth muscle cells by too much cholesterol in the cells. Current treatments to help patients who suffer from atherosclerosis related conditions include lifestyle and diet changes, medications such as statins and PCSK9 inhibitors, and in more severe cases, procedures to open blocked arteries. However, researchers said, lifestyle changes may not always help, and current medications have side effects or can be prohibitively expensive. Researchers also told that there are a lot of drugs on the market that block the smooth muscle cell pathway & now that they know this buildup can be blocked by targeting smooth muscle cells. People can use medication that is already available and target this pathway to help patients with atherosclerotic plaque buildup. Researchers are hopeful these findings can translate to clinical care.

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                        Diabetes remission after gastric bypass surgery

A newly developed test could help doctors more accurately predict whether individuals who undergo gastric bypass surgery will experience a remission of type 2 diabetes within two years of the procedure. The test, which measures blood levels of ceramides, a waxy, fat-like substance similar to cholesterol, can also be used to assess the likelihood that a gastric bypass patient will have a recurrence of type 2 diabetes within a decade. In previous studies, researchers found that ceramides can reduce the amount of insulin a body can produce or use, increasing the likelihood that a person will develop type 2 diabetes & decided to examine the association between ceramides, diabetes, and severe obesity. More than 24 million Americans are severely obese with a body mass index (BMI) of 35 or higher, according to the American Society for Metabolic and Bariatric Surgery (ASMBS). As a result, many of them have a substantial risk of developing type 2 diabetes, heart disease, and other severe conditions. For some of these individuals, gastric bypass surgery is often the best option. In some cases, patients can shed more than 30% of their body weight after surgery and keep it off for at least seven years, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Diabetes is less common after gastric bypass but predicting which patients will have a remission of the disease or a later recurrence has been challenging. The researchers chose to have two control groups to account for the possibility that those who were denied insurance coverage were more motivated to diet, exercise, and engage in other weight-loss strategies than those who had no interest in gastric bypass. Overall, the scientists found that low ceramide levels prior to gastric bypass surgery predicted which patients would achieve remission of the diabetes two years later. Of the 67 gastric bypass patients who had diabetes prior to surgery, 73% either had transient or sustained remission of their type 2 diabetes. However, those individuals with high ceramides did not achieve diabetes remission, regardless of weight change. Among its limitations, the study did not include a group of lean individuals. As a result, they were unable to determine if ceramide levels influence diabetes progression beyond a severely obese population. The researchers also did not prevent participants from pursuing weight loss interventions or lifestyle changes beyond the scope of the study, which focused specifically on Roux-en-Y, the most common gastric bypass surgery. While the data linking high ceramide levels to diabetes is strong, more research is needed before routine ceramide testing can be recommended.

SOURCE: Science Daily News, June 2022

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                              Tumor 'signatures' could provide key to accurate treatment for cancers

Scientists have found a way to identify and interpret 'signatures' that reveal the complex genetic causes of some of the deadliest cancers which often have a survival rate of less than 10%. Currently, scientists use individual genetic changes to develop mutational signatures, which can be used to understand the origin of a cancer, and to predict how a cancer progresses. However, so far, there has not been a framework to interpret the larger, more complex patterns of genetic changes seen in chromosome instability in the same way. Chromosomal instability is a common feature of cancer, occurring in around 80% of tumors, but this jumble of fragments can be difficult to read, making it hard to understand exactly what types or patterns of instability are present in any given tumor. Instead, tumors are divided into broad categories of having either high or low amounts of chromosomal instability. Cancers with high levels of chromosomal instability are extremely deadly, often having survival rates of less than 10%. As such, understanding and treating chromosomal instability is central to improving the outcomes for millions of cancer patients worldwide. Researchers investigated patterns of chromosomal instability across 7,880 tumors, representing 33 types of cancer, such as liver and lung cancer, from The Cancer Genome Atlas. By analyzing the differences in the number of repetitions of sequences of DNA within the tumors, they were able to characterize 17 different types of chromosomal instability. These chromosomal instability signatures were able to predict how tumors might respond to drugs, as well as helping in the identification of future drug targets. The more complex the genetic changes that underlie a cancer, the more difficult they are to interpret and the more challenging it is to treat the tumor. This is tragically clear from the very low survival rates for cancers that arise as a result of chromosomal instability. This discovery offers hope that this information can turn things around, providing much more sophisticated and accurate treatments.

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          Pregnancy with polycystic ovary syndrome at risk of heart complications during delivery

Common hormone disorder among women of reproductive age has been linked to an increased risk of adverse cardiovascular events and pregnancy outcomes at the time of birth. Polycystic ovary syndrome (PCOS) affects an estimated 5%-13% of women in the general population. Building on previous research that shows PCOS is linked to future cardiovascular disease risks later in life, the new findings reveal that it can also significantly increase heart problems among pregnant women during delivery. These problems include pre-eclampsia, peripartum cardiomyopathy, heart failure, abnormal heart rhythms and venous thromboembolism, compared with women without PCOS. Oftentimes, women with PCOS are understandably concerned about the immediate effects, like an irregular menstrual cycle, excess body hair, weight gain and acne. However, the long-term cardiovascular complications are also a serious problem. The prevalence of PCOS and obesity among those with the hormone disorder increased significantly during the study period. During that same time period, obesity also skyrocketed from 5.7% to 28.2% among women with PCOS. Researchers note that some of the increase in PCOS may be due to better detection and diagnosis. After adjusting for age, race, other disorders not related to PCOS, insurance coverage and income, PCOS remained an independent predictor of heart complications during delivery compared with women who did not have the hormone disorder. Complications included preeclampsia, heart failure, abnormal heart rhythms, weakened heart, and higher risk of developing blood clots. Women with PCOS were overall older and had a higher prevalence of diabetes, obesity and high cholesterol. The study also found Black women with PCOS were at greater risk for preeclampsia and other adverse outcomes. This study shows that PCOS is indeed a risk factor for acute cardiac complications at the time of delivery and should be taken seriously. In a separate analysis published in the Journal of Women's Health, scientists found that women with PCOS are two times more likely to have coronary artery calcification (CAC), a marker of subclinical atherosclerosis. It is a marker of atherosclerosis, even without symptoms, and a reliable predictor of cardiovascular disease risk. Women with PCOS are at an increased risk for dyslipidemia, type 2 diabetes, hypertension and heart disease. Detecting CAC early in women with PCOS is a key to preventing future cardiovascular disease risk.

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