Heart Disease

Heart disease is a very prominent issue in the United States, as it is one of the leading causes of deaths. According to the CDC, 1 in every 4 deaths is caused by heart disease. The most common is coronary artery disease, which is caused by plaque buildup. Other types of heart disease include arrhythmia, dilated cardiomyopathy, myocardial infarcation, and congenital heart disease. The last is a general term for heart deformities present since birth and can include a range of different issues, such as septal defects, obstruction defects, and cyanotic heart disease. Zebrafish are a favored model for all of these diseases, due to their easy to access embryo and ability to regenerate.

Common Heart diseases

Coronary artery disease

Coronary artery disease is the most common type of heart disease and leading cause of death in the US

in both men and women. It develops when major blood vessels that supply the heart with oxygen (coronary) are blocked by plaque build up. The plaque narrows the arteries and decreases blood flow to the heart. This leads to chest pain, shortness of breath. A complete blockage can cause a heart attack. This disease develops over decades, so often it goes unnoticed until a significant blockage or heart attack occurs.

Risk factors: Age (getting older), sex (male), family history, smoking, high blood pressure, high blood cholesterol levels, diabetes, physical inactivity, high stress.

Treatments: Lifestyle changes, Beta blockers, cholesterol modifying medications

Zebrafish as a model: Zebrafish can be used to study coronary artery disease, but are not the best model for it as unlike mammals, which develop a coronary system during embryogenesis, zebrafish start this development  1–2 month post hatching.  This restricts the study of coronary artery disease to adult mostly to adult zebrafish.

Arrhythmia

Arrhythmia is a problem with the rate or rhythm of your heartbeat. Your heart can beat too quickly (tachycardia), slowly (bradycardia), or with an irregular pattern. The most common type is called atrial fibrillation, which causes an irregular and fast heart beat. Symptoms include skipping beats, lightheadedness or dizziness, chest pain, shortness of breath, and sweating. Congenital heart defects often affect heart rhythm, as well as other factors such as having a heart attack or smoking.

Risk factors: Coronary artery disease, High Blood Pressure, Diabetes, Smoking, Obesity, drug abuse, stress, sleep apnea

Treatments: Cardioversion, pacemaker, implantable cardioverter-defibrillator (ICD) or surgery

Zebrafish as a model: Zebrafish are currently being used for in vivo screening to discover novel anti-arrhythmic agents. A paper discussing this use can be found here.

Dilated cardiomyopathy

Cardiomyopathy is a general term for abnormalities of the heart muscle itself. A dilated cardiomyopathy is when the ventricle, usually the left ventricle, thins and is unable to pump blood as well as a healthy heart. This may not cause symptoms, but can be life threatening as it is a common cause of heart failure. Dilated cardiomyopathy may contribute to arrhythmias, blood clots or sudden death. Common symptoms are fatigue, shortness of breath, reduced ability to exercise, swelling in legs, ankles, or feet, swelling of abdomen, chest pain, and heart murmurs.

Risk factors: Diabetes, obesity, high blood pressure, alcohol abuse, infections, complications of late-stage pregnancy.

Treatments: ACE inhibitors, Beta blockers, Biventricular pacemakers, heart transplant

Zebrafish as a model: In zebrafish a gene known as titin was discovered to provide architectural support to maintain the sarcomeric organization. A mutation in this gene leads to a weakly contractile heart and pericardial edema. This gene can lead to dilated cardiomyopathy. The paper discussing this discovery can be found here.

Myocardial Infarcation

A myocardial infarcation is more commonly known as a heart attack. It occurs when the flow of blood

to the heart is blocked, most often from coronary arteries, as described above. The plaque will eventually breakaway and form a clot that can damage or destroy part of the heart muscle. Common signs are pressure/pain in chest or arms that may spread to neck, jaw or back, nausea or heartburn, shortness of breath, cold sweat, sudden dizziness. The symptoms can be very variable, but generally the first warning sign is recurrent chest pain. If experiencing a heart attack taking an aspirin can help reduce heart damage by stopping the blood from clotting.

Risk factors: Age, poor diet, inactivity, smoking, high blood pressure, family history

Treatments: Blood thinners, beta-blockers, ACE inhibitors, thrombolytics

Zebrafish as a model: Zebrafish have regenerative properties that allow them to regenerate their heart after injury. This process is being studied to try and apply these regenerative properties to the human heart. A video discussing this can be found here.

Congenital Heart Defects

A congenital heart defect is a problem with the structure of the heart that is present at birth. More about these defects here.

Zebrafish as a model: Zebrafish have been a useful model to understand heart development and the mechanisms associated with congenital heart defects. They have been useful for studying the genetic basis of a variety of specific congenital heart defects, for instance the gene GATA4 found in zebrafish has been found to be associated with ASD and VSD. A review here goes into more specifics.