Creative Minds: Exploring the Role of Immunity in Hypertension

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.

Continue reading

Missing Genes Point to Possible Drug Targets

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.

Continue reading

A Look Inside a Beating Heart Cell

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.

Continue reading

Snapshots of Life: Green Eggs and Heart Valves

three-day old chicken embryo

Credit: Jessica Ryvlin, Stephanie Lindsey, and Jonathan Butcher, Cornell University, Ithaca, NY

What might appear in this picture to be an exotic, green glow worm served up on a collard leaf actually comes from something we all know well: an egg. It’s a 3-day-old chicken embryo that’s been carefully removed from its shell, placed in a special nutrient-rich bath to keep it alive, and then photographed through a customized stereo microscope. In the middle of the image, just above the blood vessels branching upward, you can see the outline of a transparent, developing eye. Directly to the left is the embryonic heart, which at this early stage is just a looped tube not yet with valves or pumping chambers.

Developing chicks are one of the most user-friendly models for studying normal and abnormal heart development. Human and chick hearts have a lot in common structurally, with four chambers and four valves pumping two circulations of blood in parallel. Unlike mammalian embryos tucked away in the womb, researchers have free range to study the chick heart in or out of the egg as it develops from a simple looped tube to a four-chambered organ.

Jonathan Butcher and his NIH-supported research group at Cornell University, Ithaca, NY, snapped this photo, a winner in the Federation of American Societies for Experimental Biology’s 2015 BioArt competition, to monitor differences in blood flow through the developing chick heart. You can get a sense of these differences by the varying intensities of green fluorescence in the blood vessels. The Butcher lab is interested in understanding how the force of the blood flow triggers the switching on and off of genes responsible for making functional heart valves. Although the four valves aren’t yet visible in this image, they will soon elongate into flap-like structures that open and close to begin regulating the normal flow of blood through the heart.

Continue reading

LabTV: Curious About Heart Failure in Young Children

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.

Continue reading