Researchers Show That The Hormone Relaxin Rejuvenates Electrophysiological Aspects Of The Heart
Source: Thailand Medical News Jan 08, 2020 4 years, 10 months, 6 days, 7 hours, 19 minutes ago
When a healthy human
heart ages, it becomes more susceptible to
cardiovascular diseases. Though researchers have discovered that
relaxin, an insulin-like hormone, suppresses atrial fibrillation (AF), inflammation, and fibrosis in aged rats, the underlying mechanisms of these benefits are still unknown.
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In a new
Scientific Reports paper, University of Pittsburgh graduate student Dr Brian Martin demonstrates how
relaxin interacts with the body's signaling processes to produce a fundamental mechanism that may have great therapeutic potential.
The research study, "
Relaxin reverses maladaptive remodeling of the aged
heart through
Wnt-signaling," was led by Dr Guy Salama, Professor of Medicine at University of Pittsburgh, and Dr Brian Martin, a graduate student researcher from the Swanson School of Engineering's Department of Bioengineering.
Dr Martin told
Thailand Medical News, "
Relaxin is a reproductive hormone discovered in the early 20th century that has been shown to suppress
cardiovascular disease symptoms. In this paper, we show that
relaxin treatment reverses electrical remodeling in animal models by activating canonical
Wnt signaling, a discovery that reveals a fundamental underlying mechanism behind
relaxin's benefits."
A more comprehensive understanding of how
relaxin interacts with the body may improve its efficacy as a therapy to treat
cardiovascular disease in humans. As the U.S. population ages, the rates of these age-associated diseases are expected to rise, requiring better treatment for this leading cause of death. According to a report from the American
Heart Association, the total direct medical costs of
cardiovascular disease are projected to increase to US$749 billion in 2035.
Dr Martin explained. "A common problem in age-associated
cardiovascular disease is altered electrical signaling required for proper
heart contraction. When ions in the
heart and their associated channels to enter or exit the
heart are disrupted, complications occur."
Professor Salama added, "Natural, healthy aging has been shown to be accompanied by changes in structure and function. For example, aged cardiomyocytes start to express embryonic contractile proteins and fewer voltage-gated Na
+ channels by unknown mechanisms. The reversal of some aspects of the aging process by
relaxin is mediated by the reactivation of
Wnt canonical
signaling which may partly explain mechanisms of the aging process."
The team's study found that
relaxin upregulated th
e prominent sodium channel, Nav1.5, in cells of
heart tissue via a mechanism inhibited by the
Wnt pathway inhibitor Dickkopf-1.
Dr Martin added, "
Wnt signaling is thought to be active primarily in the developing
heart and inactive later in life. However, we show that
relaxin can reactivate
Wnt signaling in a beneficial way to increase Nav1.5. Increased Nav1.5 is associated with better electrical signaling in the
heart may reduce susceptibility to cardiac rhythm disorders. Further, we show that
relaxin can also reverse the age-associated reduction in cell adhesion molecules and cell-cell communication proteins. In summary,
relaxin appears to reverse problematic reductions or pathological reorganization of vital cardiac
signaling proteins."
Although these data provide new insight into
relaxin's mechanisms of action, further work is needed to understand the precise steps required for
relaxin to alter
Wnt signaling and if steps can be taken to directly alter
Wnt signaling to provide its beneficial effects.
Reference: Brian Martin et al, Relaxin reverses maladaptive remodeling of the aged heart through Wnt-signaling, Scientific Reports (2019). DOI: 10.1038/s41598-019-53867-y
