Heart failure affects over 23 million people worldwide and despite progress in diagnosis and treatment, the 5-year mortality rate for heart failure patients remains high (45-60%). Recent research explored the potential of exercise to protect against heart failure.
Heart failure occurs when the heart is damaged or weakened and is not strong enough to properly pump blood around the body. The most common causes of heart failure are either a heart attack (myocardial infarction) or high blood pressure (hypertension). Other less common causes include diabetes, high blood cholesterol, excessive use of alcohol or drugs, thyroid diseases and heart valve diseases.
As more people survive heart attacks, the number of people susceptible to heart failure rises. As serious condition with no cure, research aimed at identifying potential therapeutic targets is a high priority. One potential therapeutic target that has been identified is the β3-adrenergeic receptor (β3-AR), a pivotal regulator of heart function in response to stress. By affecting muscle contraction, they act to lessen the heart’s workload by decreasing the rate and strength of the heartbeat.
Lifestyle is another important aspect of treatment. Exercise has many beneficial effects on the cardiovascular system and decreases the incidence of heart diseases. In patients with stable heart failure, exercise can also relieve symptoms, improve their quality of life and reduce the chance of mortality. Nitric oxide synthase (NOS) and nitric oxide (NO) have been shown to play an important role in exercise-mediated heart protection, however, the mechanism remains unclear.
Previous studies have suggested that β3-ARs are associated with NO/NOS activation (which increases during exercise) and a recent study by Wang and colleagues published in PLOS ONE hypothesized that the β3-ARs-NO-NOS pathway is activated during aerobic exercise to protect against heart failure and cardiac hypertrophy (thickening of the heart muscle walls).
A mouse model with heart failure was treated with moderate aerobic exercise (consisting of swimming for 9 weeks) and/or the β3-AR specific inhibitor (which inhibits the function of β3-ARs). Mice with heart failure that underwent exercise showed improved dilated left ventricular function and reduced hypertrophy. Treatment with the β3-ARs specific inhibitor abolished NOS/NO activation and thereby reduced protection from heart failure and hypertrophy. The decreased NO production also led to an increase in the production of reactive oxygen species (ROS), which can lead to oxidative stress induced damage.
This suggests that β3-ARs stimulation is required for cardioprotective effects and can be attributed to the equilibrium of NO and ROS production, with exercise playing a pivotal role in maintaining this balance. Hence, the mechanism responsible for protective effects such as improved heart function and alleviated dilation of the left ventricle heart chamber and hypertrophy in mice with heart failure could be associated with the activation of the β3-ARs-NO-NOS pathway. Therefore, supporting evidence that β3-ARs are indeed potential therapeutic targets for treatment of heart diseases and heart failure. This study also supports the important role aerobic exercise plays in maintaining heart health, particularly for patients diagnosed with heart failure.
Written by Lacey Hizartzidis, PhD
Wang B, Xu M, Li W, Li X, Zheng Q, Niu X (2017) Aerobic exercise protects against pressure overload-induced cardiac dysfunction and hypertrophy via β3-AR-nNOS-NO activation. PLoS ONE 12(6): e0179648.
Heart Conditions, Heart Failure. Heart and Stroke Foundation of Canada website www.heartandstroke.ca. Accessed June 23, 2017.