Myocardial infarction, or a heart attack, remains the most common cause of heart failure (HF) worldwide. Although there are treatments that aid in overall heart health, there are few preventative therapies for heart failure after a significant heart attack. Now, researchers at Baylor College of Medicine have found a potential treatment that has shown promising results in mice.
Their study, “A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction,” was published in the journal Proceedings of the National Academy of Sciences and led by Bert O’Malley, MD, professor of molecular and cellular biology at Baylor.
“Heart failure after a significant heart attack is a leading cause of death in humans. It often occurs over a few years; a person becomes weaker, and weaker and eventually they die,” explained O’Malley. “In the mouse model, our team has been able to show that MCB-613 decreases damaging remodeling when given within hours after a myocardial infarction, thereby inhibiting the subsequent development of heart failure.”
Their findings reveal stimulation of a steroid receptor coactivator, SRC-3, by a molecule known as MCB-613 after a heart attack, prevented the scar and maladaptive repair of heart tissue that can lead to heart failure.
Previous work from the researchers and other laboratories have demonstrated that SRCs are involved in heart development and in mitigating cardiac dysfunction in cardiac injury models.
“We reasoned that MCB-613 could ameliorate recovery after ischemia-induced MI. To test this, MCB-613 or vehicle control was administered to mice following myocardial injury induced by a highly experienced surgeon who permanently ligated the left anterior descending (LAD) coronary artery, a commonly used preclinical MI model for testing cardiovascular therapeutic interventions,” noted the researchers.
The molecule stimulates SRC-3, which initiates a series of tissue repair and modulation of the inflammatory response. The researchers also found that after treating the mice model with MCB-613, there were no significant signs of toxicity.
“The clinical implications of this discovery are significant. I have cared for many patients with advanced heart failure, and if we can modulate the natural history of this disease at all, we will lessen the number one cause of human death and avoid a significant amount of human suffering,” said Clifford Dacso, MD, professor of molecular and cellular biology and medicine.
Their findings demonstrate that MCB-613 acts on heart tissue repair and regeneration after a severe heart attack, but the researchers stated that more studies are needed to fully understand the safety and efficacy before the therapy is used in humans.
“Our study shows promise to address the unmet need for treatments to prevent damage to heart tissue following a heart attack. These findings pave the way for discovery of additional treatments to target chronic heart disease progression,” said Lisa Mullany, PhD, assistant professor of molecular and cellular biology and first author on the study.
The researchers concluded that their findings demonstrates that administration of a single therapeutic chemical immediately following acute ischemic cardiac injury, acts to preserve functional myocardium and attenuate detrimental, fibrotic, and inflammatory remodeling of the heart.