For decades, cardiac researcher James McCully, PhD, has been spellbound by the idea of using mitochondria, the “batteries” of the body’s cells, as a therapy to boost heart function. Finally, a clinical trial at Boston Children’s Hospital is bringing his vision — a therapy called mitochondrial transplantation — to life.
Mitochondria, small structures inside all of our cells, synthesize the essential energy that our cells need to function. In the field of cardiac surgery, a well-known condition called ischemia often damages mitochondria and its mitochondrial DNA inside the heart’s muscle cells, causing the heart to weaken and pump blood less efficiently. Ischemia, a condition of reduced or restricted blood flow, can be caused by congenital heart defects, coronary artery disease and cardiac arrest.
For the smallest and most vulnerable patients who are born with severe heart defects, a heart-lung bypass machine called extracorporeal membrane oxygenation (ECMO) can help restore blood flow and oxygenation to the heart. But even after blood flow has returned, the mitochondria and their DNA remain damaged.
“In the very young and the very old, especially, their hearts are not able to bounce back,” says McCully.
Ischemia can be fatal for the tiniest patients
After cardiac arrest, for instance, a child’s mortality rate jumps to above 40 percent because of ischemia’s effects on mitochondria. If a child’s heart is too weak to function without the support of ECMO, his or her risk of dying increases each additional day spent connected to the machine.
But what if healthy mitochondria could come to the rescue and replace the damaged ones? …
On average, one in four people who have a heart attack sustain long-lasting damage to the mitral valve, which has the important job of making sure blood pumps through the heart’s ventricles in the right direction. If the valve is damaged, the heart’s pumping efficiency is reduced and blood can flow backward, which can lead to heart failure and death.
Now, a team of collaborators from Boston Children’s Hospital, Massachusetts General Hospital and Brigham and Women’s Hospital has shown, for the first time, that it’s possible to treat and even prevent mitral valve damage after heart attack with an FDA-approved, anti-hypertension drug called losartan. Their findings are published in the Journal of the American College of Cardiology. …
The average human has 60,000 miles of blood vessels coursing through their body. There are a number of mechanisms the body uses to keep that vast vascular network healthy, including a tiny fat molecule, a lipid called S1P, that plays a particularly important role.
S1P receptors dot the surface of the endothelium, a layer of cells that line the inside of all the body’s blood cells. Together, these so-called endothelial cells form a barrier between the body’s circulating blood and surrounding tissue. When S1P molecules activate their receptors, it suppresses endothelial inflammation and generally helps regulate cardiovascular health.
Now, researchers led by Timothy Hla, PhD, from the Boston Children’s Hospital Vascular Biology Program, report a novel therapeutic fusion that could trigger increased S1P receptor activity and recover blood vessel health following the onset of hypertension, atherosclerosis, stroke, heart attack and other cardiovascular diseases. …
Heart attacks cause the death of billions of the heart’s muscle cells. If these cardiomyocytes could be made to regenerate after an infarct, the heart could potentially be mended and its function restored.
Researchers have struggled to find the right approach to cardiac regeneration. Cell transplants have been tried, but the cells don’t engraft well long term and haven’t shown efficacy. Gene therapy to spur regeneration has been tested in animals, but dosage is hard to control and there’s a risk of genes going where they shouldn’t, causing tumors and other problems. Protein drugs have been tried, but they have short half-lives, being degraded or eliminated by the body before they can do much good. They are also hard to target to the heart.
A more recent approach to cardiac regeneration is to stimulate the body itself—and, specifically, progenitor cells— to repair the heart from within. …
Grab a garden hose. Put your thumb over the end, but not all the way, and turn the water on. What happens? The water coming out of the hose gets squeezed as it tries to push past your thumb, putting a lot of force on the molecules in the water and making a big spray.
Now do the same thing with an artery: Partially block it with a clot and let blood flow through it. In this case, the force you’ve created in the artery could be lethal—creating fertile ground for blood clots that could lead to a stroke or heart attack.
People who have had a heart attack or have coronary artery disease often sustain damage that weakens their heart. Milder forms of heart failure can be treated with medications, but advanced heart dysfunction requires surgery or heart transplant. A team of physicians, engineers and materials scientists at Children’s Hospital Boston and MIT offers two alternative ways to strengthen weakened, scarred heart tissue — both involving nanotechnology.
One approach blends nanotechnology with tissue engineering to create a heart patch laced with gold whose cells all beat in time – as shown in the above video.
The other uses minute nanoparticles that can find their way to dying heart tissue, carrying stem cells, growth factors, drugs and other therapeutic compounds. …
While many of us recall that President Franklin Delano Roosevelt had polio, few remember that he died in 1945 from another cause: stroke. The sentiment of his physician — that it “had come out of the clear sky” — reflected the prevailing view that heart attack and stroke were bolts from the blue that doctors could act on only after the event.
But a few mavericks challenged this “salvage” paradigm, establishing the Framingham Heart Study in 1948 to identify predictors of cardiovascular events. One leading maverick, Dr. William Kannel, who passed away last month, coined the term “risk factors” to describe these predictors. Acting on the insight that controlling risk factors could prevent cardiovascular disease saved the lives of more than 150,000 Americans from heart disease alone between 1980 and 2000.
Judging by the surviving medical records, Roosevelt’s stroke may have been preventable with treatment for one such risk factor, hypertension. How different would the world have been had his persistent high blood pressure been treated?
The world is different now, not all for the better. High blood pressure has been attacking more and more children over the last 30 years, …