heart attack Archives - Sanford Burnham Prebys
Institute News

NIH grant aims to boost heart muscle

AuthorMonica May
Date

August 23, 2019

Heart disease is the number one killer of Americans. Now, the National Institutes of Health (NIH) has awarded a four-year grant totaling nearly half a million dollars to Sanford Burnham Prebys to find medicines that could help people repair damaged heart muscle—and potentially reduce the risk of heart attack or other cardiovascular events. 

“Each year we lose far too many loved ones to heart attacks and other heart conditions,” says grant recipient Chris Larson, PhD, adjunct associate professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys. “Now, we have the opportunity to find medicines that may help more people live long, active lives by strengthening their heart muscles.”

Nearly half of American adults—approximately 120 million people—have cardiovascular disease, according to the American Heart Association and NIH. The condition occurs when blood vessels that supply the heart with oxygen and nutrients become narrowed or blocked, increasing risk of a heart attack, chest pain (angina) or stroke. Current medications for cardiovascular disease can lower blood pressure or thin the blood to minimize risk. Still, five years after a heart attack, 47% of women and 36% of men will die, develop heart failure or experience a stroke. No medicines that repair heart muscle exist. 

To identify drugs that may stimulate heart muscle growth, Larson and his team will screen hundreds of thousands of compounds against human heart muscle cells, called cardiomyocytes. The work will be done in collaboration with Alexandre Colas, PhD, assistant professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys, who developed the high-throughput screening system that will be employed.

Once the scientists identify drug candidates that promote heart muscle growth, they will study these compounds in additional cellular and animal models of heart disease in the hopes of uncovering insights into the biology behind the repair process. 

“After experiencing a heart attack or other cardiovascular event, many people live in fear that it will happen again,” says Colas. “Today we embark on a journey toward a future where people living with cardiovascular disease don’t have to be afraid of a second heart attack.”

Institute News

Promising target for blocking buildup of fatty plaques in arteries

AuthorJessica Moore
Date

July 22, 2016

Every 34 seconds, someone in the US has a heart attack or stroke. New research from the laboratory of Erkki Ruoslahti, MD, PhD, distinguished professor in the NCI-designated Cancer Center, could lead to treatments that lower that frequency.

Heart attacks and strokes are caused by a blocked artery, which cuts off blood supply to a part of the heart or brain. These blockages occur when atherosclerotic plaques—deposits of inflamed, fat-containing cells surrounded by fibrous material inside arteries—rupture and seed blood clots. In a study published in the Journal of Controlled Release, Ruoslahti’s team shows that a specific peptide blocks expansion of these plaques at advanced stages.

“Our findings demonstrate the relevance of a new target, p32, to slowing the deposition of plaque,” said Zhi-Gang She, PhD, staff scientist in Ruoslahti’s lab and co-lead author of the paper. “We’re hopeful that drugs that act on this protein would help lower the risk for heart attacks and stroke.”

The details

The new study used a peptide called LyP-1, a ring of nine amino acids that Ruoslahti’s group has worked with for many years. LyP-1 binds to p32, a protein that’s normally located inside cells, but is found on the surface of tumor cells and active macrophages.

“Macrophages drive plaque enlargement by taking up fats and promoting inflammation, and we knew from our other investigations that LyP-1 can trigger cell death in macrophages,” explained Ruoslahti. “We thought that LyP-1 might eliminate macrophages from plaques, which would slow the advance of atherosclerosis.”

Their results confirmed this expectation—the LyP-1 peptide greatly reduced the size of plaques in mice when it was administered at advanced stages.

“Eliminating macrophages from arterial plaque is like cutting off the roots of a plant,” said She. “Not only does that get rid of a portion of the plaque, but because macrophages feed it by taking up lipids, it also keeps the plaque from getting larger.”

Clinical relevance

“The peptide itself is not a candidate drug,” added Ruoslahti. “It can only be given by injection, which isn’t practical for a chronic disease like atherosclerosis. However, we have identified small molecules that interact with p32 in a similar way to LyP-1, so they could form the basis of a drug that’s taken as a pill.”

“The key to making sure this treatment strategy is safe is confirming that it doesn’t make the plaques more likely to rupture,” commented She. “We didn’t see anything indicating that LyP-1 makes plaques less stable, but future studies should explore that issue further.”

The paper is available online here.

Institute News

Scientific breakthrough may limit damage caused by heart attacks

AuthorJessica Moore
Date

June 30, 2016

A research advance from the Sanford Burnham Prebys Medical Discovery Institute (SBP) and Stanford University could lead to new drugs that minimize the damage caused by heart attacks. The discovery, published in Nature Communications, reveals a key control point in the formation of new blood vessels in the heart, and offers a novel approach to treat heart disease patients.

“We found that a protein called RBPJ serves as the master controller of genes that regulate blood vessel growth in the adult heart,” said Mark Mercola, PhD, professor in SBP’s Development, Aging, and Regeneration Program and jointly appointed as professor of medicine at Stanford University, senior author of the study. “RBPJ acts as a brake on the formation of new blood vessels. Our findings suggest that drugs designed to block RBPJ may promote new blood supplies and improve heart attack outcomes.”

In the US, someone has a heart attack every 34 seconds. The ensuing loss of heart muscle, if it affects a large enough area, can severely reduce the heart’s pumping capacity, which causes labored breathing and makes day-to-day tasks difficult. This condition, called heart failure, arises within five years in at least one in four heart attack patients.

The reason heart muscle dies in a heart attack is that it becomes starved of oxygen—a heart attack is caused by blockage of an artery supplying the heart. If heart muscle had an alternative blood supply, more muscle would remain intact, and heart function would be preserved. Many researchers have therefore been searching for ways to promote the formation of additional blood vessels in the heart.

“Studies in animals have shown that having more blood vessels in the heart reduces the damage caused by ischemic injuries, but clinical trials of previous therapies haven’t succeeded,” said Ramon Díaz-Trelles, PhD, staff scientist at SBP and lead author of the study. “The likely reason they have failed is that these studies have evaluated single growth factors, but in fact building blood vessels requires the coordinated activity of numerous factors. Our data show that RBPJ controls the production of these factors in response to the demand for oxygen.

“We used mice that lack RBPJ to show that it plays a novel role in myocardial blood vessel formation (angiogenesis)—it acts as a master controller, repressing the genes needed to create new vessels,” added Diaz-Trelles. “What’s remarkable is that removing RBPJ in the heart muscle did not cause adverse effects—the heart remained structurally and functionally normal in mice without it, even into old age.”

“RBPJ is a promising therapeutic target. It’s druggable, and our findings suggest that blocking it could benefit patients with cardiovascular disease at risk of a heart attack. It may also be relevant to other diseases,” commented Pilar Ruiz-Lozano, PhD, associate professor of pediatrics at Stanford and adjunct professor at SBP, co-senior author. “Inhibitors of RBPJ might also be used to treat peripheral artery disease, and activators might be beneficial in cancer by inhibiting tumor angiogenesis.”

The paper is available online here.

Institute News

Hearts build new muscle with this simple protein patch

Authorsgammon
Date

September 15, 2015

An international team of researchers has identified a protein that helps heart muscle cells regenerate after a heart attack. Researchers also showed that a patch loaded with the protein and placed inside the heart improved cardiac function and survival rates after a heart attack in mice and pigs. Continue reading “Hearts build new muscle with this simple protein patch”

Institute News

New compound shows promise for safe, effective treatment of heart attack and stroke

AuthorGuest Blogger
Date

February 17, 2015

Heart attack and ischemic stroke affect hundreds of thousands of Americans every year and are leading causes of death in the United States. Both of these conditions are caused by blood clots that block vessels and interrupt blood flow to the heart or the brain, respectively. Antiplatelet therapies such as aspirin prevent clotting by decreasing the activity of blood cells called platelets, thereby lowering the risk of dying from a heart attack or having a stroke. But these drugs can cause serious side effects, such as gastrointestinal toxicity, abnormally low blood cell counts, and bleeding. Therefore, there is a strong need for research aimed at better understanding the molecular mechanisms leading to platelet activation in order to develop improved therapies.

Continue reading “New compound shows promise for safe, effective treatment of heart attack and stroke”