- Cardiac hypertrophy is the abnormal enlargement, or thickening, of the muscles of the heart and can lead to heart failure. At the cellular level, cardiomyocyte hypertrophy is the abnormal thickening of the cells in the heart.
- A new study in mice found the FDA-approved antiplatelet medication sarpogrelate significantly suppressed cardiomyocyte hypertrophy.
- Additional research is needed to determine if sarpogrelate may be an effective low-cost treatment for people with heart failure.
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DALLAS, Aug. 23, 2021 — Sarpogrelate, an antiplatelet medication, has potential as a new heart failure therapy and, according to researchers, could potentially decrease health care costs associated with cardiovascular disease, according to preliminary animal research presented at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2021. The meeting is virtual, Aug. 23-25, and offers the latest research on basic and translational cardiovascular science.
Cardiac hypertrophy is the abnormal enlargement, or thickening, of the muscles of the heart and can lead to heart failure. One way that cardiac hypertrophy occurs is when cardiomyocytes, the cells that are responsible for contracting the heart muscle, become thicker than normal. The thickened cells become stiff, reducing the amount of blood pumped out to the body with each contraction of the heart (heartbeat). This cellular contraction eventually leads to the progression of heart failure. Cardiac hypertrophy is the most common form of genetic heart disease, and it is estimated that 1 in every 500 people are affected, yet a large percentage are undiagnosed. People with cardiac hypertrophy are at higher risk of blood clots, stroke, heart failure, cardiac arrest and other heart-related complications.
“Heart failure costs the United States billions each year in treatment, management, health care costs and missed days of work. Additionally, the cost of new drug development increases every year,” said Kana Shimizu, M.S., B.S.Pharm., is a Ph.D. student at the University of Shizuoka in Shizuoka, Japan. “We investigated whether existing, approved medicines could be repurposed as heart failure treatments at lower costs.”
Researchers screened a variety of compounds that suppress cardiomyocyte hypertrophy and identified the antiplatelet medication sarpogrelate as a potential candidate. Sarpogrelate is a serotonin receptor antagonist that has been found to cause vasodilation, or widening of the blood vessels, as well as reduce cell damage.
This study examined the effects of sarpogrelate on cardiomyocyte hypertrophy and the development of heart failure in mice. First, cultured cardiomyocyte cells were treated with 1 microgram, or 1 μM, of sarpogrelate and then stimulated with various hypertrophic agents to induce cell growth. The sarpogrelate significantly suppressed cardiomyocyte hypertrophy induced by each stimulus.
Mice then underwent a transverse aortic constriction (TAC), a procedure that induces cardiac hypertrophy. One day after the operation, the mice were randomly divided into three groups: either an oral dose of sarpogrelate at 1 mg/kg or 5 mg/kg daily for eight weeks, or the control group that did not receive sarpogrelate.
At the end of the eight-week study period, the mice who received 5 mg/kg of sarpogrelate daily were significantly less likely to develop heart failure after the TAC procedure. Echocardiographic analysis showed that the higher dose of sarpogrelate suppressed a TAC-induced increase in ventricular wall thickness and other measures of cardiac hypertrophy, such as the ratio of heart weight to body weight.
“These findings suggest that oral administration of this approved antiplatelet medication significantly suppresses cardiomyocyte hypertrophy and the development of heart failure in mice,” said Shimizu. “Sarpogrelate may be an effective, low-cost agent for heart failure therapy, however, more research is needed to understand the mechanisms of this medication and the protein or proteins it targets to inhibit the thickening of the cardiac cells.”
Co-authors are Masafumi Funamoto, Ph.D., B.S.Pharm.; Yoichi Sunagawa, Ph.D.; Yasufumi Katanasaka, Ph.D., B.S.Pharm.; Yusuke Miyazaki, B.S.Pharm.; Noriyuki Murai, B.S.Pharm.; Satoshi Shimizu, M.S.; Koji Hasegawa, M.D., Ph.D.; and Tatsuya Morimoto, M.D., Ph.D. The authors’ disclosures are listed in the abstract.
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The American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions (BCVS) is the world’s premier meeting dedicated to the latest advances in basic and translational cardiovascular science. The virtual meeting is Monday-Wednesday, Aug. 23-25, 2021. The primary goal of the meeting is to convene scientists from around the world with the common goal to discover pathways to cardiovascular therapeutics and promoting cardiovascular health. Sessions are focused on new therapies and insights in cardiovascular disease, as well as research in fields like microRNAs, cardiac gene and cell therapy, cardiac development, as well as tissue engineering and iPS cells. The BCVS 2021 Scientific Sessions program, planned by the American Heart Association’s Council on Basic Cardiovascular Sciences, is of special interest to basic cardiovascular scientists, molecular/ cellular biologists, physiologists, translational investigators, clinical trialists, practicing cardiologists, cardiovascular nurses and pharmacists. Follow the conference on Twitter at #BCVS21.
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