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Creative Minds: Exploring the Role of Immunity in Hypertension

Posted on by Dr. Francis Collins

Meena Madhur

Meena Madhur / Credit: John Russell

If Meena Madhur is correct, people with hypertension will one day pay as much attention to their immune cell profiles as their blood pressure readings. A physician-researcher at Vanderbilt University School of Medicine, Nashville, Madhur is one of a growing number of scientists who thinks the immune system contributes to—or perhaps even triggers—hypertension, which increases the risk of stroke, heart disease, kidney disease, and other serious health problems.

About one of every three adult Americans currently have hypertension, yet a surprising number don’t know they have it and less than half have their high blood pressure under control—leading many health experts to refer to the condition as a “silent killer”[1,2]. For many folks, blood pressure control can be achieved through lifestyle changes, such as losing weight, exercising, limiting salt intake, and taking blood pressure medicines prescribed by their health-care provider. Unfortunately, such measures don’t work for everyone, and some people continue to suffer damage to their kidneys and blood vessels from poorly controlled hypertension.

Madhur wants to know whether the immune system might be playing a role, and whether this might hold some clues for developing new, more targeted ways of treating high blood pressure. To get such answers, this practicing cardiologist will use her 2016 NIH Director’s New Innovator Award to conduct sophisticated, single-cell analyses of the immune systems of people with and without hypertension. Her goal is to produce the most comprehensive catalog to date of which human immune cells might be involved in hypertension.


Creative Minds: The Human Gut Microbiome’s Top 100 Hits

Posted on by Dr. Francis Collins

Michael Fishbach

Michael Fishbach

Microbes that live in dirt often engage in their own deadly turf wars, producing a toxic mix of chemical compounds (also called “small molecules”) that can be a source of new antibiotics. When he started out in science more than a decade ago, Michael Fischbach studied these soil-dwelling microbes to look for genes involved in making these compounds.

Eventually, Fischbach, who is now at the University of California, San Francisco, came to a career-altering realization: maybe he didn’t need to dig in dirt! He hypothesized an even better way to improve human health might be found in the genes of the trillions of microorganisms that dwell in and on our bodies, known collectively as the human microbiome.


Missing Genes Point to Possible Drug Targets

Posted on by Dr. Francis Collins

Human knockout projectEvery person’s genetic blueprint, or genome, is unique because of variations that occasionally occur in our DNA sequences. Most of those are passed on to us from our parents. But not all variations are inherited—each of us carries 60 to 100 “new mutations” that happened for the first time in us. Some of those variations can knock out the function of a gene in ways that lead to disease or other serious health problems, particularly in people unlucky enough to have two malfunctioning copies of the same gene. Recently, scientists have begun to identify rare individuals who have loss-of-function variations that actually seem to improve their health—extraordinary discoveries that may help us understand how genes work as well as yield promising new drug targets that may benefit everyone.

In a study published in the journal Nature, a team partially funded by NIH sequenced all 18,000 protein-coding genes in more than 10,500 adults living in Pakistan [1]. After finding that more than 17 percent of the participants had at least one gene completely “knocked out,” researchers could set about analyzing what consequences—good, bad, or neutral—those loss-of-function variations had on their health and well-being.


Are E-cigarettes Leading More Kids to Smoke?

Posted on by Dr. Francis Collins

Cigarettes vs. E-Cigarettes

Thinkstock\MilknCoffee

Today, thanks to decades of educational efforts about the serious health consequences of inhaled tobacco, fewer young people than ever smoke cigarettes in the United States. So, it’s interesting that a growing of number of middle and high school kids are using e-cigarettes—electronic devices that vaporize flavored liquid that generally contains nicotine.

E-cigarettes come with their own health risks, including lung inflammation, asthma, and respiratory infections. But their supporters argue that “vaping,” as it’s often called, might provide an option that would help young people steer clear of traditional cigarettes and the attendant future risks of lung cancer, emphysema, heart disease, and other serious health conditions. Now, a new NIH-funded study finds that this is—pardon the pun—mostly a pipe dream.

Analyzing the self-reported smoking behaviors of thousands of schoolkids nationwide, researchers found no evidence that the availability of e-cigarettes has served to accelerate the decline in youth smoking. In fact, the researchers concluded the opposite: the popularity of e-cigarettes has led more kids—not fewer—to get hooked on nicotine, which meets all criteria for being an addictive substance.


Precision Medicine: Using Genomic Data to Predict Drug Side Effects and Benefits

Posted on by Dr. Francis Collins

Gene Variant and Corornary Heart Disease

People with type 2 diabetes are at increased risk for heart attacks, stroke, and other forms of cardiovascular disease, and at an earlier age than other people. Several years ago, the Food and Drug Administration (FDA) recommended that drug developers take special care to show that potential drugs to treat diabetes don’t adversely affect the cardiovascular system [1]. The challenge in implementing that laudable exhortation is that a drug’s long-term health risks may not become clear until thousands or even tens of thousands of people have received it over the course of many years, sometimes even decades.

Now, a large international study, partly funded by NIH, offers some good news: proof-of-principle that “Big Data” tools can help to identify a drug’s potential side effects much earlier in the drug development process [2]. The study, which analyzed vast troves of genomic and clinical data collected over many years from more than 50,000 people with and without diabetes, indicates that anti-diabetes therapies that lower glucose by targeting the product of a specific gene, called GLP1R, are unlikely to boost the risk of cardiovascular disease. In fact, the evidence suggests that such drugs might even offer some protection against heart disease.

Genetic approaches have increasingly been used to identify potentially promising new drug targets. In the study reported in Science Translational Medicine, researchers led by Robert Scott and Nick Wareham from the University of Cambridge, England, and Dawn Waterworth from GlaxoSmithKline, King of Prussia, PA, also wanted to explore whether genomic data could yield important clues about the potential side effects of drugs targeting particular genes.


A Look Inside a Beating Heart Cell

Posted on by Dr. Francis Collins

Caption: Microtubules (blue) in a beating heart muscle cell, or cardiomyocyte. Credit: Lab of Ben Prosser, Ph.D., Perelman School of Medicine, University of Pennsylvania

You might expect that scientists already know everything there is to know about how a healthy heart beats. But researchers have only recently had the tools to observe some of the dynamic inner workings of heart cells as they beat. Now an NIH-funded team has captured video to show that a component of a heart muscle cell called microtubules—long thought to be very rigid—serve an unexpected role as molecular shock absorbers.

As described for the first time recently in the journal Science, the microtubules buckle under the force of each contraction of the muscle cell before springing back to their original length and form. The team also details a biochemical process that allows a cell to fine-tune the level of resistance that the microtubules provide. The findings have important implications for understanding not only the mechanics of a healthy beating heart, but how the abnormal stiffening of heart cells might play a role in various forms of cardiac disease.


Obesity Research: Study Shows Significant Benefits of Modest Weight Loss

Posted on by Dr. Francis Collins

5% weight loss

For the one in three American adults who are obese, recommendations to lose substantial amounts of weight through a combination of diet and exercise can seem daunting and, at times, hopeless. But a new study should come as encouraging news for all those struggling to lose the extra pounds: even a modest goal of 5 percent weight loss delivers considerable health benefits.

In the NIH-funded study, people with obesity who lost just 5 percent of their body weight—about 12 pounds on average—showed improvements in several risk factors for type 2 diabetes and heart disease. They also showed metabolic improvements in many parts of the body, including the liver, pancreas, muscle, and fat tissue. While people who lost additional weight enjoyed further improvements in their health, the findings reported in the journal Cell Metabolism show that sometimes it really does pay to start small [1].


LabTV: Curious About Heart Failure in Young Children

Posted on by Dr. Francis Collins

Josh Maxwell

Growing up in Pittsburgh, Josh Maxwell enjoyed romping around outdoors. He was an adventurous kid who liked to catch live frogs and snakes, lug them home, and surprise his parents with the latest creepy find. Maxwell rode his curiosity for nature to a bachelor’s degree in biology from Allegheny College, Meadville, PA. He then went on to earn a Ph.D. in cell and molecular physiology from Loyola University Chicago Stritch School of Medicine.

Maxwell, the focus of our latest LabTV video, is now a research scientist in the lab of Michael Davis at Emory University, Atlanta, where he studies pediatric heart failure. Maxwell grows cardiac cells in tissue culture and tries to fix the defects that lie within. What’s driving this important research is that a heart transplant remains the only option to save the lives of many kids born with severe congenital heart problems. In addition to shortages of donated organs, undergoing such a major operation at such a tender age can take a real toll on the children and their families. Maxwell wants to be a part of discovering non-surgical alternatives to regenerate cardiac tissue and one day repair a damaged heart for a lifetime.


Blood Sugar Control for Diabetes: Asking the Heart Questions

Posted on by Dr. Francis Collins

Glucose testing

Credit: Thinkstock

When most people think about risk factors for cardiovascular disease, they likely think of blood pressure readings or cholesterol levels. But here’s something else that should be high on that list: diabetes. That’s because people with diabetes are roughly twice as likely to die of heart disease than other folks [1]. Yet the issue of how best to help such people lower their cardiovascular risks remains a matter of intense debate. Some studies have suggested that part of the answer may lie in tightly controlling blood sugar (glucose) levels with a strict regimen of medications and monitoring [2]. Other research has shown that the intense effort needed to keep blood glucose levels under tight control might not be worth it and may even make things worse for certain individuals [3].

Now, a follow up of a large, clinical trial involving nearly 1,800 U.S. military veterans with type 2 diabetes—the most common form of diabetes—provides further evidence that tight blood glucose control may indeed protect the cardiovascular system. Reporting in The New England Journal of Medicine [4], researchers found a significant reduction in a composite measure of heart attacks, strokes, heart failure, and circulation-related amputations among the vets who maintained tight glucose control for about five and a half years on average. What’s particularly encouraging is most of the cardiovascular-protective benefit appears to be achievable through relatively modest, rather than super strict, reductions in blood glucose levels.


Revisiting Resveratrol’s Health Claims

Posted on by Dr. Francis Collins

Photo of red wine and dark chocolate
Credit: Jill George, NIH

Over the past decade or so, a lot of us have been led to believe that certain indulgences—such as a glass of Pinot noir or a piece of dark chocolate—can actually be health-promoting. That’s because a number of studies had suggested that red wine, chocolate, and other foods containing the antioxidant resveratrol might lower the risk of heart disease, cancer, and other age-related maladies. But now comes word that a diet rich in resveratrol may not automatically translate into better health.


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