Effects of Epigenetics in Cardiovascular Disease & Research

In biology, epigenetics is the study of heritable changes that do not involve alterations in the DNA sequence. The Greek prefix ‘epi’ means over, outside of, or around. Thus, its definition is the feature of the genetic code that exists or develops in addition to traditional genetic inheritance.

Epigenetics is, in essence, the study of how things like lifestyle choices and the environment can cause changes that affect the way your genes work, including what diseases you become predisposed to. Most epigenetic changes are reversible; however, their effects can worsen or cause diseases that are not.

Epigenetics has emerged as a powerful tool to aid in the therapeutic treatment of cardiovascular disease by looking closely at the epigenetics of cardiovascular patients and customizing treatment plans based on someone’s unique epigenetic factors.

Studies That Link Epigenetics and Cardiovascular Disease

Epigenetics was initially studied in patients with cardiovascular disease to better understand their prominent role in inflammation and vascular involvement. These studies in cardiovascular patients showed a significant number of certain epigenetic modifications affecting the development and progression of cardiovascular disease.

In the case of cardiovascular hypertrophy, epigenetics studies found that cardiac hypertrophy is linked with histone acetylation, implicating both histone acetyltransferases (HATs) and histone deacetylases (HDACs).

Cardiac Arrhythmias

Epigenetics has also been studied in afflictions like cardiac arrhythmias. Atrial fibrillation is one of the most common heart arrhythmias, particularly in older patients, and can be deadly. In a study done on its role in atrial fibrillation, transgenic mice were programmed to develop cardiac hypertrophy, and then treated with an epigenetic approach, “Liu and colleagues showed that an injection of a specific HDAC inhibitor reverses atrial fibrosis and diminishes atrial fibrillation vulnerability following an electrical stimulation.” (1)

Among miRNAs that have been widely studied in experimental environments, miR-1 was found to be essential in normal electrophysiological conduction. When miR-1 was deleted in rodents, the rate of sudden death was much higher. This points to the idea that the miR-1 subtype of miRNAs is essential to healthy cardiac rhythms and lowering levels of miR-1 could signal an oncoming arrhythmia. Epigenetic interventions can more effectively return the heart back to a normal state when combined with traditional methods.

Atherosclerosis

In atherosclerosis (hardening of the arteries or artery disease), epigenetic studies reveal some key factors to recognize developing atherosclerosis, sometimes before the patient even feels symptoms. DNA methylation, miRNAs, and epigenetic mechanisms have all been described in atherosclerosis. Two studies were done that show coexisting DNA methylation alongside atherosclerotic lesions in rodents. Interestingly, it was observed that DNA methylation could often be detected in animals far before the anatomical presentation of the disease itself. In short – DNA methylation testing could stand as a powerful screening tool to determine the early stages of atherosclerosis.

Diabetes and Cardiovascular Disease

In studying the relationship between diabetes and cardiovascular disease, epigenetics can be used to demonstrate the effect of untreated or poorly treated diabetes on worsening heart disease. In a study conducted and published by Louisa Villeneuve and colleagues, they found connections between diabetes and the inflammatory epigenetic reactions that can be caused by high glucose.

This study found that the occurrence of inflammatory genes in vascular cells that were exposed to high glucose for extended periods was increased. (2) Conversely, they found that histone H3 (specifically, H3K9me3), which is known to guard the body against the biochemical effects of diabetic inflammation, were decreased in environments in which they had to succumb to high glucose. The finding shows that uncontrolled glucose levels (usually caused by uncontrolled or poorly treated diabetes) can simultaneously cause inflammatory reactions while hindering the effectiveness of key histones like H3K9me3.

In all studies that have been completed, one thing was clear. Epigenetic changes are a clear indicator that can tell us important information about a patient’s ongoing cardiovascular disease or likelihood of developing impending cardiovascular disease.

Conclusion on Epigenetics and Cardiovascular Research

Epigenetics are genetic changes that happen in reaction to external factors. These external factors are usually caused by environmental or lifestyle exposures. Epigenetic changes can be important ‘warning signs that a disease is worsening or about to occur. Furthermore, by studying epigenetics in relation to heart disease, we can get a better idea of what prevention and intervention tactics should be taken.

Epigenetic factors and expressions are somewhat unique and can vary from patient to patient, but overall, there are quantifiable patterns of what role epigenetics plays in cardiovascular disease. Studying these micro-changes can make a big difference in preserving the quality of life in patients with cardiovascular disease and aid in early detection of patients with epigenetic risk factors for the disease.

Cardiovascular Research and Training Institute

Researchers at the Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI) are focused on understanding the epigenetic factors that alter transcription and thereby cardiac physiology during the development of arrhythmias, cardiac hypertrophy, and heart failure. Specifically, research at CVRTI has centered on understanding the role of lysine methyltransferases in modifying histones within the nucleosome, characteriz ing specific histone modifications that are differentially regulated during disease, and identifying the role of transcription factors  in pathological remodeling and reverse remodeling . These studies have utilized zebrafish , mouse models and human induced pluripotent stem cells  as transgenic models of disease to further our understanding of these key processes. By incorporating cutting-edge technology with novel animal models of disease, the epigenetics research at CVRTI is making significant contributions not only to basic science, by elucidating the fundamental basis of gene expression and transcriptional regulation in the cardiomyocyte, but also to the clinical realm by identifying key regulators of cardiac pathophysiology that may also protect the heart from ischemic injury or heart failure.    

What is the Difference Between Pacemakers and Defibrillators?

The heart is the most important muscle in the body—it’s the one that keeps us alive. When the heart can’t keep up due to disease, damage, or other issues, technology is available to help. Two of the most common devices associated with heart attacks, heart disease, and other heart conditions are pacemakers and defibrillators. But what are these tools, and what makes them different? How does each provide the assistance that the heart needs to continue beating (since that’s what both were designed for)?

In this blog, we’ll take a look at defibrillators and pacemakers to explain when and how they’re most commonly used and what types of patients are candidates for treatment with either device.

Defibrillators

Also known as ICDs, implantable cardioverter defibrillators are implanted devices that are designed to shock the heart to assist in restoring its rhythm to normal. They are usually prescribed for those who at risk of having life threatening arrhythmias. These devices can detect the dangerous arrhythmias and convert the rhythm back to normal using electric shock.

Anyone who is at risk from arrhythmia-induced death can benefit from an ICD, including people with cardiomyopathy, a history of cardiac arrest, severely reduced heart function, or genetic diseases like Long QT syndrome, ARVC, cardiac sarcoidosis, etc. that can cause ventricular arrhythmias (fast rhythm coming from the ventricles or the bottom chambers of the heart).

ICDs are usually implanted below the collar bone. An ICD is larger than a pacemaker and about the size of a pager. The defibrillators are used for tachycardia or fast heartbeats, but these devices can also provide dual function and serve as a pacemaker to correct issues with slow or weaker heartbeats, too.

Defibrillators include the generator along with the leads that are used to detect rhythm and deliver the appropriate shock to the heart as needed. The generator goes below the collar bone, and it houses the computer, capacitor, and the battery. The lead are wires that run through a large vein that goes to the heart so that they can deliver the shock needed to restore the rhythm. These devices offer a longer lifespan in general. For some patients they also can offer a better quality of life and longer lifespan but those do require slightly more invasive surgical methods.

Risk of procedure include infection, bleeding, and the potential for unnecessary shocks. For the most part, risks are minimal, and most people see more improvement than anything.

Pacemakers

The pacemaker is also an implanted battery-operated device, smaller than the ICDs, that assists the heart in beating at an acceptable rate. It is used for people who have a slower heart rate.

Implanting a pacemaker requires a minor surgery and a short hospital stay just like the ICDs. They can improve people’s quality of life in several ways by providing the electrical impulses the heart needs to keep the heart beating and can’t produce on its own.

The pacemaker is also implanted below the collar bone and features leads and a generator. The generator is where the information and battery are held, and the lead wires are run through a large vein that goes to the heart so that they can deliver the impulses that give the heart the reminder to beat. There are newer pacemakers available now that don’t have a lead and are referred to as “leadless” pacemakers. Leadless pacemakers are implanted directly in the heart itself and function as a complete unit.

In rare instances, infection or other complications can occur, but they are rare. Some people also worry about the interference of electronics or magnets, but again, that’s a minimal risk for the most part.

Conclusion

Ultimately, patients are best served by discussing their condition with their cardiologists to determine the right solution. Understanding the differences between these devices and the conditions they treat can help you make the most informed decision about keeping your heart (or your loved one’s) healthy and beating strong for as long as possible.

These electric devices are constantly evolving and improving, so it will likely only be a matter of time before there are even better solutions available. The heart is a strong muscle, typically, but even it is not impervious to damage and ill health as time goes on. For those with heartbeat irregularities, a pacemaker or defibrillator implant could be the solution they need to provide a better quality of life and give them a better chance of living longer.

Cardiovascular Research and Training Institute

At CVRTI, we are investigating multiple aspects related to pacing and defibrillation. We are actively investigating more efficient ways  to pace patients out of dangerous arrhythmias using the highly efficient conduction system in the heart. This approach can potentially lower the chance of getting shocked, which is uncomfortable for patients. There is also active investigation exploring many different pathways to improve muscle function in heart failure  using gene therapy based medicine . These novel therapeutics will lower the risk of developing dangerous cardiac arrhythmias. There is also more basic science investigation exploring genetic and molecular basis of developing heart failure and arrhythmias, with the development of intravenous therapies to stop dangerous arrhythmias as they occur.