Key result
L-cysteine supplementation significantly attenuated isoproterenol-induced cardiac remodeling, fibrosis, and systolic dysfunction in mice.
Why the study?
Heart failure mechanisms remain incompletely understood, limiting treatments; elevated CDO1 activity was hypothesized to deplete steady-state cysteine and impair ROS scavenging and cardiac function.
Does L-cysteine supplementation prevent isoproterenol-induced cardiac remodeling and dysfunction in mice?
Does L-cysteine supplementation prevent isoproterenol-induced cardiac remodeling and dysfunction in mice?
L-cysteine supplementation reverses isoproterenol-induced cardiac remodeling and oxidative stress in a murine model, highlighting the CDO1 pathway as a potential novel therapeutic target for adrenergic-mediated heart failure.
Hypothesis-generating for L-cysteine in adrenergic heart failure models; leaves open translation to human disease.
Despite considerable scientific and clinical efforts, heart failure (HF) still has a poor prognosis and is a leading cause of death worldwide. The molecular mechanisms underlying HF are not fully understood, limiting treatment options. We recently identified cysteine dioxygenase type 1 (CDO1) as a novel target candidate in the failing heart of mice, with aberrant CDO1 pathway targets also noted in human HF. CDO1 oxidizes cysteine to cysteine sulfinic acid, thus regulating cellular redox balance. We hypothesized that elevated CDO1 activity in the failing heart depletes steady-state cysteine, thereby depleting the cellular glutathione pool, causing impairment in reactive oxygen species (ROS) scavenging and cardiac function. Adult (4-6 months), and aged (18-20 months) male and female mice were administered the β-agonist isoproterenol (ISO) for one week with and without L-cysteine supplemented in the drinking water at 200mg/L. Supplementation of L-cysteine attenuated whole heart and left ventricle weight when indexed to the body size compared to ISO alone. ISO-induced changes in systolic function (cardiac output, fractional shortening, ejection fraction) were significantly reversed. Cysteine attenuated ISO-induced cardiac fibrosis. In line with cysteine regulating oxidative stress, we observed significantly lower malondialdehyde (MDA) levels as marker of ROS. Together, our results demonstrate that cysteine supplementation can reverse ISO-induced changes in the heart, thus representing a novel target for adrenergic-mediated HF. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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Yusifov et al. (2026) studied Isoproterenol-induced cardiac remodeling. L-cysteine vs. Isoproterenol (ISO) alone was evaluated on Cardiac remodeling and systolic function. L-cysteine supplementation significantly attenuated isoproterenol-induced cardiac remodeling, fibrosis, and systolic dysfunction in mice.
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