Immune Cells Mistake Heart Attacks for Viral Infections

A study led by Kevin King, a bioengineer and physician at the University of California San Diego, has found that the immune system plays a surprising role in the aftermath of heart attacks.  The research could lead to new therapeutic strategies for heart disease.

The team, which also includes researchers from the Center for Systems Biology at Massachusetts General Hospital (MGH), Brigham and Women’s Hospital, Harvard Medical School, and the University of Massachusetts, presents the findings in the Nov. 6 issue of Nature Medicine.

Ischemic heart disease is the most common cause of death in the world and it begins with a heart attack. During this process, heart cells die, prompting immune cells to enter the dead tissue, clear debris and orchestrate stabilization of the heart wall.

But what is it about dying cells in the heart that stimulates the immune system? To answer this, researchers looked deep inside thousands of individual cardiac immune cells and mapped their individual transcriptomes using a method called single cell RNA-Seq. This led to the discovery that after a heart attack, DNA from dying cells masquerades as a virus and activates an ancient antiviral program called the type I interferon response in specialized immune cells. The researchers named these “interferon inducible cells (IFNICs).”

When investigators blocked the interferon response, either genetically or with a neutralizing antibody given after the heart attack, there was less inflammation, less heart dysfunction, and improved survival. Specifically, blocking antiviral responses in mice improved survival from 60 percent to over 95 percent. These findings reveal a new potential therapeutic opportunity to prevent heart attacks from progressing to heart failure in patients.

“We are interested to learn whether interferons contribute to adverse cardiovascular outcomes after heart attacks in humans,” said King, who did most of the work on the study while he was a cardiology fellow at Brigham and Women’s Hospital and at the Center for Systems Biology at MGH in Boston.

The immune system has evolved innate antiviral programs to defend against a diverse range of invading pathogens. Immune cells do this by detecting molecular fingerprints of pathogens, activating a protein called IRF3, and secreting interferons, which orchestrate a defense program mediated by hundreds of interferon-stimulated genes. Investigators found that surprisingly, the antiviral interferon response is also turned on after a heart attack despite the absence of any infection. Their results point to dying cell DNA as the cause of this confusion because the immune system interprets it as the molecular signature of a virus.

Surprisingly, the immune cells participating in the interferon response were a previously unrecognized subset of cardiac macrophages. These cells could not be identified by conventional flow sorting because unique markers on the cell surface were not known. By using single cell RNA Seq, an emerging technique that combines microfluidic nanoliter droplet reactors with single cell barcoding and next generation sequencing, the researchers were able to examine expression of every gene in over 4,000 cardiac immune cells and found the specialized IFNIC population of responsible cells.

Future studies will aim to better understand the interferon response and the IFNIC cell type and explore their roles in the infarcted and remodeling heart. The team is also working to understand the interferon response in other tissues and diseases where cell death occurs.

Bariatric surgery lowers cancer risk for severely obese patients

Severely obese patients who undergo bariatric surgery lower their risk of developing cancer by at least a third, according to a University of Cincinnati (UC) College of Medicine researcher leading a large retrospective cohort study of patients in the western United States.

“We found having bariatric surgery is associated with a reduced risk of cancer, especially obesity-associated cancers including postmenopausal breast cancer, endometrial cancer, pancreatic cancer and colon cancer,” explains Daniel Schauer, MD, associate professor in the UC Division of General Internal Medicine and lead researcher. “What’s surprising is how great the risk of cancer was reduced.”

The findings were recently published online in the Annals of Surgery.

The study reviewed medical data of 22,198 individuals who had bariatric surgery and 66,427 nonsurgical patients between 2005 and 2012 with follow-up through 2014. It pulled data from large integrated health insurance and health care delivery systems from five study sites operated by Kaiser Permanente–Southern California, Northern California, Oregon, Colorado and Washington.

More than 80 percent of patients in the study were women.

Patients undergoing bariatric surgery had a 33 percent lower risk of developing any cancer during follow-up, according to the published findings. Schauer says the benefit is greatest among obesity-associated cancers. The risk of postmenopausal breast cancer dropped by 42 percent and while the risk for endometrial cancer dropped 50 percent in severely obese patients. The risk of colon cancer dropped 41 percent while the risk of pancreatic cancer was lowered by 54 percent.

“Cancer risks for postmenopausal breast cancer and endometrial cancer are closely related to estrogen levels,” says Schauer. “Having weight loss surgery reduces estrogen level.”

Bariatric surgery helps reduce the risk of diabetes and insulin levels which may be a risk factor for pancreatic cancer, while the mechanisms for colon cancer are more complicated, says Schauer.

“I think considering cancer risk is one small piece of the puzzle when considering bariatric surgery, but there are many factors to consider. Reductions in diabetes, hypertension and improvements in survival and quality of life are reason enough,” says Schauer. “The study provides an additional reason to consider bariatric surgery.”

The study found no significant association between bariatric surgery and cancer risk among men. Schauer says that may be because the vast majority of study patients are female and at least two of the cancers most impacted by bariatric surgery, postmenopausal breast cancer and endometrial cancer, affect women only.

Multivariable Cox proportional-hazards models were used to examine the incidence of cancer up to 10 years after bariatric surgery compared to the matched nonsurgical patients. After a mean follow-up of 3.5 years, researchers identified 2,543 incident cancers.

About 15 million adults in the United States suffer from severe obesity, which is defined as having a body mass index of greater than 35 kg/m2. Obesity and cancer are closely linked. Obesity is associated with up to 40 percent of all cancers diagnosed in the United States, says Schauer.

Study: Breastfeeding Moms May Be at Lower Risk of Heart Attack and Stroke

We have known for a long time that breastfeeding is healthy for babies; however studies have shown that it can provide long term health benefits for the moms too. This new information comes from recent research published in the Journal of the American Heart Association. The comprehensive study followed 300,000 adult women in China.

Previous studies showed different health benefits from breastfeeding were short term including lower cholesterol, blood pressure, glucose levels, and weight loss after pregnancy. However, this study explored long term results for the 300,000 subjects who had breastfed their babies. The research was performed by researchers from the University of Oxford, Peking University, and the Chinese Academy of Medical Sciences. The 300,000 women that took part in the study were between 30 and 79 years old and from 10 urban and rural areas across China, they tracked their health through hospital records and death registries and were part of the prospective China Kadoorie Biobank of half a million adults. The observations were as follows:

  • Nearly all gave birth and 97 percent of the women breastfed each of their babies for an average of 12 months.
  • Compared to women who had never breastfed, mothers who ever breastfed their babies had a 9 percent lower risk of heart disease and an 8 percent lower risk of stroke.
  • Among mothers who breastfed each of their babies for two years or more, heart disease risk was 18 percent lower and stroke risk was 17 percent lower than among mothers who had never breastfed.
  • Each additional 6 months of breastfeeding per baby was associated with a 4 percent lower risk of heart disease and a 3 percent lower risk of stroke.

More research is needed to determine a better correlation between breastfeeding and the health results since it is possible that women who breastfed might also engage in other healthy behaviors that might also lower their risk for cardiovascular diseases. However, the researchers did take into consideration other lifestyle choices and a range of risk factors so the observed benefits from breastfeeding were calculated independently of the other lifestyle factors.

A research fellow from The George Institute for Global Health at the University of Oxford, Dr. Sanne Peters was the study author. He explains, “Although we cannot establish the causal effects, the health benefits to the mother from breastfeeding may be explained by a faster “reset” of the mother’s metabolism after pregnancy.” It is believed that breastfeeding might eliminate the stored fat accrued during pregnancy faster and more completely and that is what leads to reduced risk of cardiovascular diseases later in life. The study co-author is Liming Li from the Peking University explains, “Nearly all women in the study were born before 1970s and the rate of breastfeeding was much higher than that in the Western populations and younger generations in China.”

The American Heart Association suggests trying to maintain breastfeeding for 12 months if possible. According to WHO’s data, about 30 percent of women in the US managed to breastfeed their baby for 12 months in 2016. In China, only 30 percent of rural women and 16 percent of urban women now managed to breastfeed their baby for 6 months or more.

This is just one of many important and informative medical research studies from The George Institute for Global Health, a health and medical research institute. Their mission is to improve the health of millions of people worldwide. One of the ways The George Institute for Global Health achieves their mission is through George Clinical, a leading contract research organization (CRO) headquartered in Sydney, Australia but with operational hubs in ten countries throughout Asia.