Heart muscle repair breakthrough reported
Following a myocardial infarction (heart attack), a portion of the heart muscle is destroyed because of loss of circulation (ischemia). This damaged area is replaced with scar tissue (fibroblasts); thus, the damaged heart loses pumping efficiency. If the heart is sufficiently damaged, heart failure and death occurs. A new study has reported a method to replace the fibroblasts with working heart muscle. Researchers at Duke University (Durham, NC) published their findings online on April 27 in the journal Circulation Research.
Embryonic stem cells are pluripotent, meaning they can be stimulated to develop into any type of tissue. However, the use of human embryos is controversial on an ethical basis and the possibility of malignant tumors developing from these cells is possible. Research is also ongoing with adult stem cells; however, they have limited capacity to develop into new tissue compared to embryonic stem cells. The Duke researchers took a new approach to growing new heart muscle; they used molecules known as miRNAs (microRNAs) to convert fibroblasts into heart muscle cells in both tissue cultures (in vitro) and in a living mouse (in vitro). The in vitro experiments improved the ability of the heart to pump blood.
The goal of the study was to develop a technique, which identified and evaluated the potential of specific microRNAs capable of inducing reprogramming of cardiac (heart) fibroblasts directly to cardiomyocytes (functioning heart muscle) in vitro and in vivo. The researchers identified a combination of several types miRNAs (1, 133, 208, and 499), which were capable of inducing direct cellular reprogramming of fibroblasts to cardiomyocyte-like cells in vitro. They went on to administer the microRNAs into ischemic mouse myocardium (heart muscle with an inadequate blood supply). They found that the miRNAs converted the cardiac fibroblasts to cardiomyocytes in the mouse heart. They noted that a genetic tracing analysis strongly suggested that induced cells are most likely of fibroblastic origin.
The authors concluded that their findings provided “proof-of-concept that miRNAs have the capability of directly converting fibroblasts to a cardiomyocyte-like phenotype in vitro.” In addition, they noted that another significant result of their study was that it was the first report of direct cardiac reprogramming in vivo. The noted that, in addition to heart muscle regeneration, their approach may have broad and important implications for therapeutic tissue regeneration in general.
Coronary heart disease is the leading cause of death and premature death in the United States. Risk factors include:
- Age: Aging increases the risk of damaged and narrowed arteries.
- Gender: Men are generally at greater risk of coronary artery disease; however, the risk for women increases after menopause.
- Family history: A family history of heart disease is associated with a higher risk of coronary artery disease, particularly if a close relative developed heart disease at an early age. The risk is highest if one’s father or a brother was diagnosed with heart disease before age 55, or one’s mother or a sister developed it before age 65.
- Smoking: Nicotine constricts your blood vessels, and carbon monoxide can damage their inner lining, making them more susceptible to atherosclerosis.
- Hypertension: Uncontrolled hypertension (high blood pressure) can result in hardening and thickening of the arteries; thus, the blood flow channel is narrowed.
- High blood cholesterol levels: High cholesterol levels can increase the risk of formation of plaques and atherosclerosis. High cholesterol can be caused by a high level of low-density lipoprotein (LDL; "bad cholesterol”). A low level of high-density lipoprotein (HDL; "good cholesterol”) can also promote atherosclerosis.
- Diabetes: Diabetes is associated with an increased risk of coronary artery disease.
- Obesity: Excess weight commonly aggravates other risk factors.
- Physical inactivity: Lack of exercise is associated with coronary artery disease as well as some of its risk factors.
- High stress: Unrelieved stress in one’s life may damage arteries; furthermore, it can aggravate other risk factors for coronary artery disease.
Reference: Circulation Research