Aortic Stenosis Overview
World-first Vascularization To Advance Global Research Into Heart Disease
Australian researchers have achieved two firsts that will assist in the global battle against heart disease: they created a tiny beating heart with its own vascular system and then uncovered how the vascular system affects inflammation-driven heart damage.
Cardiovascular diseases (CVDs) are one of the leading causes of death globally. According to the World Health Organization (WHO), CVDs claim an estimated 17.9 million lives yearly. Death rates due to CVDs are expected to rise, given our aging population and the impact of lifestyle-related risk factors.
CVDs include any condition that affects the heart or circulation, such as heart attack and coronary artery disease, high blood pressure, stroke, and vascular dementia. Given the prevalence of CVDs, it's important that research continues to uncover new ways of preventing, diagnosing and treating this group of diseases.
Australian researchers have contributed to the acceleration of research in the area of heart disease with their creation of a tiny heart organoid.
Organoids are tiny structures that mimic human organs. They're grown in a lab, using human pluripotent stem cells, which can be generated using 'reprogrammed' skin or blood cells.
"Each organoid is only about the size of a chia seed, measuring just 1.5 millimeters [0.06 in] across, but inside are 50,000 cells representing the different cell types that make up the heart," said James Hudson, corresponding author of the study.
Here, researchers created a tiny beating organoid, which is nothing new. But, for the first time, they were able to successfully incorporate vascular cells, the cells that line blood vessels, bringing the model heart even closer to replicating the real thing.
"Incorporating the vascular cells for the first time in our mini heart muscles is very significant because we found they had a key role in the biology of the tissues," Hudson said. "Vascular cells made the organoids function better and beat strongly. This has really opened up our ability to better understand the heart and accurately model disease."
The added bonus of vascular cells meant that the researchers could investigate how they affect inflammation, which can cause the heart to stiffen. In another first, the researchers uncovered the key role the vascular system plays in inflammation-driven heart muscle injury.
"When we stimulated inflammation in our mini heart muscles, we found the vascular cells played a central role," said Hudson. "We only saw the stiffening in the tissues that had the vascular cells. The cells sensed what was happening and changed their behavior, and we identified that the cells release a factor called endothelin that mediates the stiffening."
The researchers say that this discovery, and the use of their novel heart organoid, could lead to new treatments for heart disease.
"That's where our new system of producing vascularized cardiac organoids will really give us an advantage because we'll be able to progress the search for new treatments much more quickly," Hudson said.
Publication of the study will help researchers worldwide create their own vascularized organoid, boosting the global effort to tackle heart disease, the researchers say. Moreover, they say their discovery could be used to create kidney and brain organoids, accelerating research into the diseases that affect those organs.
The study was published in the journal Cell Reports, and the below video from the QIMR Berghofer shows the novel human heart organoid in action. James Hudson, one of its creators and authors of the current study, explains how the organoid was created and how it might be used.
Vascularised heart organoids video V2
Source: QIMR Berghofer
Treatment Options For Peripheral Artery Disease
Making changes to your diet and lifestyle can help manage peripheral artery disease. Other treatments, including medications and surgical procedures, may also be recommended.
Peripheral artery disease (PAD) is a condition that affects the arteries all around your body, not including those that supply the heart (coronary arteries) or the brain (cerebrovascular arteries). This includes arteries in your legs, arms, and other parts of your body.
PAD develops when fatty deposits or plaque accumulate on the walls of your arteries, which causes inflammation in the walls of the arteries and reduces blood flow to these parts of the body.
Reduced blood flow can damage tissue, and if left untreated, lead to amputation of a limb.
PAD affects over 230 million people worldwide and occurs more often in older adults.
Risk factors for PAD include smoking, high blood pressure, and a history of diabetes or heart disease.
Symptoms can include:
PAD can raise the risk of a stroke or heart attack because people who have atherosclerosis in these arteries can also have it in other arteries. However, treatments are available to prevent life-threatening complications.
This article will take a closer look at some effective ways to treat and manage PAD.
The goal of treatment for PAD is to improve blood flow and reduce blood clots in the blood vessels. Treatment also aims to lower blood pressure and cholesterol to prevent further PAD.
Since plaque accumulation causes this disease, a doctor may prescribe a statin, which is a type of cholesterol-lowering drug that can reduce inflammation.
Statins can improve the overall health of your arteries and reduce your risk of a heart attack and stroke.
A doctor may also prescribe a medication to reduce your blood pressure. Examples include:
A doctor can also recommend drugs to prevent blood clots, such as a daily aspirin or another prescription medication or a blood thinner.
If you have diabetes, it's important to take your medication as directed to maintain a healthy blood sugar level.
If you have pain in your limbs, a doctor may also prescribe medication such as cilostazol (Pletal) or pentoxifylline (Trental). These medications can help your blood flow more easily, which can reduce pain.
Increasing your activity level can improve your symptoms of PAD and help you feel better.
Regular physical activity helps stabilize blood pressure and cholesterol levels. This reduces the amount of plaque in your arteries and improves blood circulation and blood flow.
A doctor may recommend treatment in a rehabilitation center where you'll exercise under the guidance of a healthcare professional. This might include walking on a treadmill or performing exercises that specifically work your legs and arms.
You can also start your own exercise routine with activities like regular walking, biking, and swimming.
Aim for 150 minutes of physical activity each week. Start slowly and gradually build up to this goal.
Smoking constricts your blood vessels, which can lead to high blood pressure. It can also increase your risk of complications like heart attack or stroke and can cause damage to the walls of the blood vessels.
Quitting smoking not only improves your overall health, but it can also restore blood flow and can slow the progression of PAD.
To quit smoking, explore different nicotine replacement options to curb your cravings, such as gums, sprays, or patches.
In addition, some medications can help you successfully quit. Consult a doctor to explore your options.
Diet also plays a big role in slowing the progression of PAD.
Eating foods high in fat or sodium can increase your cholesterol levels and drive high blood pressure. These changes lead to increases in plaque production in your arteries.
Incorporate more healthy foods into your diet, such as:
Try to reduce your intake of foods that increase cholesterol and blood fat levels, including foods high in fat or sodium. Some examples of foods to limit or avoid include:
If left untreated, PAD can lead to tissue death and possible amputation. Because of this, it's important to manage diabetes and keep your feet in good condition.
If you have PAD and diabetes, it may take longer for injuries on your feet or legs to heal. As a result, you may be at an increased risk for infection.
Follow these steps to keep your feet healthy:
See a doctor if a sore on your foot doesn't heal or worsens.
In severe cases of PAD, medication and lifestyle changes may not improve your condition. If so, a doctor may recommend surgery to help restore proper blood flow to a blocked artery.
Procedures can include angioplasty with a balloon or a stent to open up an artery and keep it open.
A doctor may also need to perform bypass surgery. This involves removing a blood vessel from another part of your body and using it to create a graft. This allows blood to flow around a blocked artery, like creating a detour.
A doctor can also inject medication into a blocked artery to break up a blood clot and restore blood flow.
Early PAD doesn't always have symptoms, and symptoms that do appear can often be subtle.
If you have risk factors for this condition and develop muscle pain, weakness in limbs, or leg cramps, see a doctor.
PAD can progress and lead to serious complications, so early treatment is important to improve your overall health.
A Heartbeat In A Dish: Growing Specialized Heart Cells
Detailed examinations of the heart have revealed the pivotal role of the left ventricle—it's the area of the heart that develops first and provides the force to pump blood around our bodies. Crucially, it is also the area most commonly implicated in heart disease and heart attacks and it is the area most prone to suffering the cardiotoxic effects of certain drugs.
Researchers at the Crick have now developed a way to grow specialized left ventricular heart muscle cells from stem cells, opening up new opportunities for research into heart disease, drug screening, and potentially the development of new treatments.
Their methods are published today in Cell Reports Methods and have also been licensed to Axol Bioscience to commercialize the protocol for the generation and sale of cardiomyocytes for R&D and the provision of contract research services, especially in field of drug screening and cardiotoxicity assays.
Growing a heartbeatThe work has been driven by Andreia Bernardo, a Wellcome Trust Career Re-Entry Fellow at the Crick who has recently started her own lab at Imperial College London. Growing left ventricular cardiomyocytes (heart muscle cells) is a complicated process, and one that is based on a detailed understanding of developmental biology, as Andreia explains.
"In order to encourage cells to specialize, you have to understand the natural developmental process. We set out to understand the different chambers of the heart—how are they formed, and what are the genes and pathways involved in their development.
"It's only with this detailed understanding of early embryonic changes, that we could apply the knowledge in stem cell models, starting with forming the correct mesoderm lineage, the first phase in cell specialization. We also found that blocking the retinoic acid pathway acts like a fail stop, preventing different types of cardiomyocyte from forming.
"What we end up with is a near homogeneous population of left ventricular cardiomyocytes that beat in synchrony. It's like a Mexican wave across the dish. We can study these cells functionally in 2D cultures and we can even make engineered heart tissues with them and measure their force and study them in this 3D environment. Surprisingly, we show that left ventricle cardiomyocytes or the engineered heart tissues generated from them are stronger and have improved structural, functional and metabolic maturity compared to the standard cardiomyocyte models."
A method 30 years in the makingAndreia's work has roots in research carried out more than 30 years ago. Jim Smith, Emeritus Scientist at the Crick, first examined molecules that drive embryonic development in the early amphibian embryo using the frog Xenopus laevis as a model.
Andreia and Jim met when they were both working at Cambridge University, and they began collaborating on research in mouse embryos, progressing the work towards human stem cells, a partnership that would continue when Jim became Director of the MRC National Institute for Medical Research, one of the Crick's founder institutes.
A culture of left ventricular cardiomyocytes beating in synchrony. Credit: The Francis Crick Institute"When I was an early career researcher I had no idea how my findings might one day be applied," says Jim. "It's very exciting seeing the molecules we first observed in frogs now being a part of this process.
"This really highlights the value of discovery research—you never know where it might lead."
It was the partnership between Andreia and Jim that pushed the research forward through challenges over the years.
"I took a long period away from work to care for my child who was very unwell and if it wasn't for Jim's support, I don't know if I would have come back," says Andreia.
"And more recently, just as we were refining our methods, we were forced to stop our research because of the pandemic. So many cultures were lost and that set us back nearly a year."
But thankfully, their team returned to the Crick and with support from the Crick translation team, found a partner in Axol Bioscience.
Ranmali Nawaratne, Senior Business Manager in the Crick translation team, said, "When Andreia and Jim brought this protocol to our team, the potential was clear. We were able to file a patent and also provide in-house translation funding that they could use to generate more data on the nature of these cardiomyocytes.
"It's been brilliant working to translate this lab discovery into a marketable method. It is exciting to see how these specialized cardiomyocytes will be applied in future research and potentially in cell therapy, in time to come."
Future applicationsThe new agreement with Axol Bioscience will allow more labs across the world to use these specialized heart cells in their own research. This could be testing the safety of different drugs or developing new drugs for the treatment of left ventricle specific diseases.
Andreia has also recently started her own research group at Imperial College where her team will use the cells to study left ventricular development, maturation and disease. Diseases like hypertrophic cardiomyopathy, a congenital heart condition affecting specifically the left ventricle, will be better modeled using this method. Her team will also be exploring if these cells have therapeutic value for treatment of heart failure.
More information: Nicola Dark et al, Generation of left ventricle-like cardiomyocytes with improved structural, functional, and metabolic maturity from human pluripotent stem cells, Cell Reports Methods (2023). DOI: 10.1016/j.Crmeth.2023.100456
Citation: A heartbeat in a dish: Growing specialized heart cells (2023, April 25) retrieved 29 April 2023 from https://phys.Org/news/2023-04-heartbeat-dish-specialized-heart-cells.Html
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